Biochimia glucidelor si lipidelor

Metabolismul acizilor grasiMetabolism acizi grasi; importanta Acetil-CoA in metabolismul lipidelor; structura generala a acizilor grasi; nomenclatura; sinteza de novo a acizilor grasi; modificari ale acizilor grasi; activare si transport acizi grasi; beta-oxidarea mitocondriala; sinteza si rolul corpilor cetonici; reglarea metabolismului acizilor grasiAutor: www-medlib.med.utah.edu

I. Significance of Fatty Acid Metabolism

OverviewEnergyIntermediates in SynthesisDiseases

Overview

Fatty acids are taken up by cells, where they may serve as precursors in the synthesis of other compounds, as fuels for energy production, and as substrates for ketone body synthesis. Ketones bodies may then be exported to other tissues, where they can be used for energy production. In addition, some cells synthesize fatty acids for storage or export.

Energy

Fats are an important source of dietary calories. Typically 30-40% of calories in the American diet are from fat. Explore

Fat is the major form of energy storage. In a typical individual the fuel reserves are distributed as follows:

fat: 100,000 kcal. protein: 25,000 kcal. carbohydrate: 650 kcal.

Intermediates in Synthesis

Fatty acids are intermediates in the synthesis of other important compounds. Examples include:

Phospholipids (in membranes). Eicosanoids, including prostaglandins and leucotrienes, which play a role in physiological

regulation.

Diseases

Some diseases involve disturbances in fatty acid metabolism. These include:

Diabetes mellitus Specific disorders of fatty acid oxidation, such as Sudden Infant Death Syndrome and Reye

Syndrome, which might be related to a deficiency of medium chain acyl CoA dehydrogenase, an important enzyme of fatty acid oxidation.

II. Acetyl CoA -- The Center of Lipid Metabolism

Overview of Acetyl CoA MetabolismPrecursors of Acetyl CoAProducts of Acetyl CoA MetabolismStructure of Acetyl CoAFunction of CoA

Overview of Acetyl CoA Metabolism

Here are the major metabolic sources of acetyl CoA and some of the pathways for which it serves as a substrate.

Precursors of Acetyl CoA

Acetyl CoA is at the center of lipid metabolism. It is produced from:

Fatty acids Glucose (through pyruvate) Amino acids Ketone bodies

Products of Acetyl CoA Metabolism

It can be converted to fatty acids, which in turn give rise to:

triglycerides (triacylglycerols) Explore phospholipids eicosanoids (e.g., prostaglandins) ketone bodies

It is the precursor of cholesterol, which can be converted to:

steroid hormones bile acids

It produces energy, generated by the complete oxidation of acetyl CoA to carbon dioxide and water through the tricarboxylic acid cycle and oxidative phosphorylation.

Structure of Acetyl CoA

The structure of Acetyl CoA consists of two parts.

1. Acetyl group 2. Coenzyme A

Beta-mercaptoethylamine Pantothenic acid (not synthesized in man -- an essential nutrient) Phosphate 3', 5'-adenosine diphosphate

Function of CoA

CoA is a commonly used carrier for activated acyl groups (acetyl, fatty acyl and others). The thioester bond which links the acyl group to CoA has a large negative standard free energy of hydrolysis (-7.5 kcal/mole). This qualifies it as a high energy bond, and explains why an acyl group attached to CoA in this manner is considered to be activated.

III. General Features of Fatty Acid Structure

OverviewCarbon-Carbon Double BondsClassification of Fatty Acids

Overview

The elements of fatty acid structure are quite simple. There are two essential features:

1. A long hydrocarbon chain o The chain length ranges from 4 to 30 carbons; 12-24 is most common. o The chain is typically linear, and usually contains an even number of carbons.

2. A carboxylic acid group

The many fatty acids which occur naturally arise primarily through variation of chain length and degree of saturation.

Carbon-Carbon Double Bonds

Carbon-carbon double bonds (unsaturations) are found in naturally occurring fatty acids. There may be one double bond or many, up to six in important fatty acids. Fatty acids with one double bond are the most prevalent in the human body, comprising about half of the total. Fatty acids with two or more double bonds occur in lesser quantities, but are extremely important.

When double bonds occur they are almost always cis. If there is more than double bond, they occur at three-carbon intervals, e.g., -C=C-C-C=C-. This is called the divinylmethane pattern.

It is so named because it is as if a methane carbon (in the center) is attached to two vinyl groups (carrying the double bonds). The pattern may be repeated to yield fatty acids with many double bonds.

Classification of Fatty Acids

One system of fatty acid classification is based on the number of double bonds.

0 double bonds: saturated fatty acids

Stearic acid is a typical long chain saturated fatty acid.

1 double bond: monounsaturated fatty acids

Oleic acid is a typical monounsaturated fatty acid.

2 or more double bonds: polyunsaturated fatty acids

Linoleic acid is a typical polyunsaturated fatty acid.

IV. Nomenclature

SystemsTrivial NamesIUPACTwo Abbreviation SystemsGreek Letters are Used in Two WaysSummary of the Four Common Systems

Systems

There are four common naming systems; three of them attempt to denote the chain length and the number and positions of any double bonds.

The first two columns show systems based on complete names, and the last two columns show systems for denoting compounds with abbreviations.

Systems: Trivial Names

Trivial names contain no clues to the structures; one must learn the name and associate it with a separately learned structure. The names typically derive from a common source of the compound or the source from which it was first isolated. For example, palmitic acid is found in palm oil, oleic acid is a major constituent of olive oil (oleum) and stearic (from the Greek word meaning solid) acid is solid at room temperature. Spiders (arachnids) contain arachidonic acid.

Systems: IUPAC

IUPAC names follow the nomenclature conventions of the International Union of Pure and Applied Chemistry. These names describe the structures in detail (if one knows the conventions), but tend to be unwieldy.

In the IUPAC system, the carboxyl carbon is denotes by the number one, and positions in the chain are denoted with reference to it. E.g. a double bond is said to be at the 9-carbon if it originates at the ninth carbon, and extends to the next (tenth) carbon in the chain.

Systems: Two Abbreviation Systems

After the common names, these are the most frequently used to denote complicated structures.

The carboxyl-reference system indicates the number of carbons, the number of double bonds, and the positions of the double bonds, counting from the carboxyl carbon (which is numbered 1,

as in the IUPAC system). It differs from the IUPAC system in that it uses a number (e.g., 16) to denote chain length instead of a name derived from Greek (e.g., hexadecanoic acid).

The omega-reference system indicates the number of carbons, the number of double bonds and the position of the double bond closest to the omega carbon, counting from the omega carbon (which is numbered 1 for this purpose). This system is useful in physiological considerations because of the important physiological differences between omega - 3 and omega - 6 fatty acids, and the impossibility to interconvert them in the human body.

Systems: Greek Letters are Used in Two Ways

Greek letters are also sometimes used to denote positions relative to the carboxyl carbon. The following diagram illustrates how Greek letters are used to denote positions relative to either end of a fatty acid chain.

The first carbon following the carboxyl carbon is the alpha carbon. The second carbon following the carboxyl carbon is the beta carbon. The last carbon in the chain, farthest from the carboxyl group, is the omega carbon.

Summary of the Four Common Systems

Here are the four commonly used ways of designating fatty acids.

V. De novo Synthesis of Fatty Acids

OverviewTissue locationsReaction sumEnzymes and Isolated ReactionsAcetyl CoA carboxylaseActivities of FA SynthaseCharacteristics of Fatty Acyl SynthaseAcetyl Groups and Reducing Equivalents

Overview

Fatty acid synthesis is the process of combining eight two-carbon fragments (acetyl groups from acetyl CoA) to form a 16-carbon saturated fatty acid, palmitate.

Palmitate can then be modified to give rise to the other fatty acids. These modifications may include:

chain elongation to give longer fatty acids, such as the 18-carbon stearate. desaturation, giving unsaturated fatty acids.

Overview: Tissue locations

Fatty acid synthesis occurs primarily in the cytoplasm of these tissues:

liver adipose (fat) central nervous system lactating mammary gland

Overview: Reaction sum

Sum of the reactions:

8 acetyl CoA + 7 ATP + 14 (NADPH + H+) -> palmitate (16:0) + 8 CoA + 7 (ADP + Pi) + 14 NADP+ + 6 H2O

This is the overall process for fatty acid synthesis. Acetyl CoA for fatty acid synthesis comes mostly from glycolytic breakdown of glucose.

Glucose Yields Acetyl CoA -- Schematic

This process is somewhat roundabout.

1. Glucose is first degraded to pyruvate by aerobic glycolysis in the cytoplasm. 2. Pyruvate is then transported into the mitochondria, where pyruvate dehydrogenase oxidatively

decarboxylates pyruvate, forming acetyl CoA and other products. 3. Acetyl CoA can then serve as a substrate for citrate synthesis. 4. Citrate, in turn, can be transported out of the mitochondria to the cytoplasm (where fatty acid

synthesis occurs), and there split to generate cytoplasmic acetyl CoA for fatty acid synthesis.

Citrate can also be oxidized by the tricarboxylic acid cycle in the mitochondria to yield energy. Notice that the need first to form citrate, then to transport it to the cytoplasm and then split it in order to get acetyl CoA for fatty acid synthesis provides several points at which control over acetyl CoA availability can be exerted.

Enzymes and Isolated ReactionsAcetyl CoA carboxylase catalyzes the reaction:

acetyl CoA + HCO3- + ATP -> malonyl CoA + ADP + Pi

Six molecules of malonyl CoA and one molecule of acetyl CoA then interact sequentially with fatty acid synthase to yield the final product, palmitate.

Fatty acid synthase is a multifunctional enzyme with seven activities.

Enzymes and Isolated Reactions: Acetyl CoA carboxylase

Acetyl CoA carboxylase has three important features.

1. It contains the prosthetic group, biotin.

o The enzyme, using its biotin prosthetic group as a carrier, transfers CO2 from bicarbonate to the acetyl group.

o Biotin is not synthesized in humans, and is an essential nutrient. 2. The carboxylation reaction is driven to completion by hydrolysis of ATP. 3. The enzyme catalyzes the rate-limiting reaction for fatty acid synthesis, and is under tight short-

term control. o It is down-regulated by:

palmitoyl CoA (endproduct regulation). phosphorylation of the enzyme (through a glucagon-cAMP cascade).

o It is up-regulated by: citrate (allosteric) dephosphorylation of the enzyme (influenced by the insulin/glucagon ratio).

To summarize, it is controlled both allosterically (citrate, palmitoyl CoA) and by covalent modification (phosphorylation/dephosphorylation).

Enzymes and Isolated Reactions: Activities of FA Synthase

The first iteration of the sequence catalyzed by this enzyme can be represented by the seven following reactions.

1. In the first reaction acetyl CoA is added to a cysteine -SH group of the condensing enzyme (CE) domain:

acetyl CoA + CE-cys-SH -> acetyl-cys-CE + CoASH

Mechanistically this is a two step process, in which the group is first transferred to the ACP (acyl carrier peptide), and then to the cysteine -SH group of the condensing enzyme domain.

2. In the second reaction malonyl CoA is added to the ACP sulfhydryl group:

malonyl CoA + ACP-SH -> malonyl ACP + CoASH

This -SH group is part of a phosphopantethenic acid prosthetic group of the ACP.

3. In the third reaction the acetyl group is transferred to the malonyl group with the release of carbon dioxide:

malonyl ACP + acetyl-cys-CE -> beta-ketobutyryl-ACP + CO2

4. In the fourth reaction the keto group is reduced to a hydroxyl group by the beta-ketoacyl reductase activity:

beta-ketobutyryl-ACP + NADPH + H+ -> beta-hydroxybutyryl-ACP + NAD+

5. In the fifth reaction the beta-hydroxybutyryl-ACP is dehydrated to form a trans- monounsaturated fatty acyl group by the beta-hydroxyacyl dehydratase activity:

beta-hydroxybutyryl-ACP -> 2-butenoyl-ACP + H2O

6. In the sixth reaction the double bond is reduced by NADPH, yielding a saturated fatty acyl group two carbons longer than the initial one (an acetyl group was converted to a butyryl group in this case):

2-butenoyl-ACP + NADPH + H+ -> butyryl-ACP + NADP+

The butyryl group is then transferred from the ACP sulfhydryl group to the CE sulfhydryl:

butyryl-ACP + CE-cys-SH -> ACP-SH + butyryl-cys-CE

This is catalyzed by the same transferase activity as was used previously for the original acetyl group.

The butyryl group is now ready to condense with a new malonyl group (third reaction above) to repeat the process.

7. When the fatty acyl group becomes 16 carbons long, a thioesterase activity hydrolyses it, forming free palmitate:

palmitoyl-ACP + H2O -> palmitate + ACP-SH

Reference: Smith S. The animal fatty acid synthase: one gene, one polypeptide, seven enzymes. FASEB J 1994 Dec;8(15):1248-1259

Enzymes and Isolated Reactions: Characteristics of Fatty Acyl Synthase

Fatty acyl synthase has three important characteristics :

1. It is essential, but not rate-limiting, for fatty acid synthesis. It is not subject to short term control. 2. ACP and the catalytic activities are on a single contiguous protein (257 kDa). 3. In animals the synthase is active only as a dimer. The malonyl/acetyl transferase, condensing

enzyme and dehydratase activities from the first subunit and all the other activities from the second subunit form one functional unit. A second functional unit forms from the remainder of the two subunits.

In contrast, bacterial activities are all on separate enzymes. Interestingly, the enoyl reductase of Mycobacterium tuberculosis is the target of isoniazid and other major antituberculosis drugs.

Acetyl Groups and Reducing Equivalents

Acetyl groups are produced in the mitochondria by pyruvate dehydrogenase, and are transported to the cytoplasm.

Citrate synthase converts acetyl CoA and oxaloacetate to citrate. Citrate exits the mitochondria on the citrate-malate antiport. In the cytoplasm citrate is cleaved by the citrate cleavage enzyme to regenerate oxaloacetate

and acetyl CoA. Oxaloacetate in the cytoplasm is reduced to malate by NADH from glycolysis; this supplies the

malate for the citrate-malate antiport.

NADPH is produced mostly by the hexose monophosphate pathway.

The malic enzyme might also contribute to NADPH production.

VI. Modification of Dietary and Endogenous Fatty Acids

OverviewElongationFatty Acid Synthesis in the Endoplasmic ReticulumMitochondrial Fatty Acid Elongation, a Minor PathwayDesaturationThe Overall ReactionSpecificity

Overview

The palmitate produced by fatty acid synthase is typically modified to give rise to the other fatty acids.

Fatty acids from dietary sources, too, are often modified.

These modifications may include:

chain elongation to give longer fatty acids desaturation, giving unsaturated fatty acids.

Elongation

Elongation can occur in most tissues; the process differs in the endoplasmic reticulum vs. the mitochondria.

Elongation: Fatty Acid Synthesis in the Endoplasmic Reticulum

In endoplasmic reticulum the reactions resemble those of de novo fatty acid synthesis.

The overall reaction:

This shows the overall process of fatty acyl elongation in the endoplasmic reticulum. The process resembles that catalyzed by fatty acyl synthase, but the individual activities appear to be on separate enzymes.

Notice that malonyl CoA is the source of the added carbons, as in de novo fatty acid synthesis.

The activities are closely associated with the endoplasmic reticulum membranes.

The activities are separable; they are not part of a multifunctional enzyme.

No ACP is involved; CoA esters are used directly.

Elongation: Mitochondrial Fatty Acid Elongation, a Minor Pathway

In the mitochondria fatty acid elongation occurs by a reversal of beta-oxidation.

This shows the overall reaction of fatty acid elongation in mitochondria. The process is essentially a reversal of beta-oxidation, except that one NADPH and one NADH are required (beta-oxidation yields two NADH). Mitochondrial fatty acid elongation acts primarily on fatty acyl CoA substrates shorter than 16 carbons.

Notice that here acetyl CoA is the source of the added carbons.

Desaturation

Desaturation of fatty acids can also occur in most tissues.

Desaturation: The Overall ReactionRCH2CH2...CH2COSCoA + NADPH + H+ + O2 -->RCH=CH...CH2COSCoA + NADP+ + 2H2O

A cis double bond is formed.

The reaction requires an electron transport system involving:

1. cytochrome b5 2. desaturase 3. NADPH-cytochrome b5 reductase

This complex system avoids generating H2O2 in the vicinity of the sensitive double bonds. The system is associated with the membranes of the endoplasmic reticulum.

Desaturation: Specificity

In humans there are four distinct desaturases, each with a different specificity:

9, 6, 5, 4 (that is, they act at the 9-, 6-, 5- or 4-carbons.) A minimum chain length of 16-18 carbons is required.

The specificity of distance from the carboxyl carbon, along with the need for a 16-18 carbon chain means that n-6 and n-3 fatty acids are not synthesized in humans. Because some of these fatty acids are metabolically essential, they must be supplied in the diet. Desaturation and 2-carbon elongation often alternate, e.g., conversion of dietary linoleic acid (18:2 9,12) to arachidonic acid (20:4 5,8,11,14), which is important because it is a precursor of eicosanoids.

18:2 9,12 --> 18:3 6,9,12 --> 20:3 8,11,14 --> 20:4 5,8,11,14 --> eicosanoids

VII. Mobilization and Transport of Adipose Fatty Acid

OverviewStorage in adipocytes as triacylglycerolAdipocytes release nonesterified fatty acids.

Overview

Fatty acids, as triacylglycerol (triglyceride), are stored in white adipose tissue. This fat storage comprises the 100,000 Kcal of energy stored as fat, mentioned at the beginning of this exercise.

Brown adipose tissue is a thermogenic tissue, and is not important in energy storage.

Storage in adipocytes as triacylglycerol

Fatty acids are stored primarily in adipocytes as triacylglycerol. Triacylglycerol must be hydrolyzed to release the fatty acids.

Adipocytes are found mostly in the abdominal cavity and subcutaneous tissue. Adipocytes are metabolically very active; their stored triacylglycerol is constantly hydrolyzed and

resynthesized.

The structure of a typical triacylglycerol (triglyceride).

Adipocytes release nonesterified fatty acids.

Nonesterified fatty acid release from the adipocytes is initiated by the action of hormone sensitive lipase (HSL), which begins to hydrolyze the stored triglyceride.

The final products of triacylglycerol hydrolysis are glycerol and nonesterified fatty acids.

HSL is activated by epinephrine, norepinephrine, ACTH and glucagon, acting via phosphorylation of the enzyme.

It is inhibited by insulin.

Nonesterified fatty acids are bound to serum albumin for transport to other tissues, where they are used.

Major target tissues are muscle and liver. At the target cells nonesterified fatty acids are taken up passively. Within the target cells they

are bound to fatty acid binding protein. Next they must be activated.

VIII. Fatty Acid Activation and Transport into the Mitochondria

OverviewActivationTransportTransport and Regeneration

Overview

Fatty acids inside the cell, like glucose, must be activated before proceeding through metabolism.

Activation consists of conversion of the nonesterified fatty acid to its CoA derivative.

The activated fatty acid may then be transported into the mitochondrion for energy production. Unlike transport across the plasma membrane, transport across the mitochondrial membrane requires a carrier.

Activation

Fatty acids are activated by fatty acyl CoA synthetase.

The reaction:

R-COOH + CoASH + ATP <--> R-CO-SCoA + AMP + PPi

The subsequent hydrolysis of PPi draws the reaction in the forward direction, maintaining a low cytosolic free fatty acid concentration:

PPi + H2O --> 2 Pi

The reaction occurs in the endoplasmic reticulum and the outer mitochondrial membrane.

Transport

The fatty acyl group is transported into the mitochondrial matrix, where it undergoes beta-oxidation.

In the intermembrane space of the mitochondria, fatty acyl CoA reacts with carnitine in a reaction catalyzed by carnitine acyltransferase I (CAT-I), yielding CoA and fatty acyl carnitine. The resulting fatty acyl carnitine crosses the inner mitochondrial membrane.

CAT-I is associated with the inner leaflet of the outer mitochondrial membrane. In liver the CAT-I reaction is rate-limiting; the enzyme is allosterically inhibited by malonyl CoA.

Malonyl CoA concentration would be high during fatty acid synthesis. Inhibition of CAT-I by

Transport and Regeneration

Fatty acyl CoA is impermeable to the inner mitochondrial membrane, so it is carried in the form of fatty acyl carnitine.

Fatty acyl carnitine is transported across the inner mitochondrial membrane in exchange for carnitine by an antiport translocase.

In the mitochondrial matrix fatty acyl carnitine reacts with CoA in a reaction catalyzed by carnitine acyltransferase II (CAT-II), yielding fatty acyl CoA and carnitine.

The fatty acyl CoA is now ready to undergo beta-oxidation.

IX. Mitochondrial beta-oxidation

OverviewFour enzymes and reactionsDehydrogenationHydration2nd dehydrogenationThiolytic cleavageComplete beta-oxidation of palmitoyl CoAAdditional EnzymesEnoyl CoAtrans- vs cisPropionyl CoASummary

Overview

Beta-oxidation is the process by which long chain fatty acyl CoA is degraded. The products of beta-oxidation are:

acetyl CoA FADH2, NADH and H+

The overall reaction, using palmitoyl CoA (16:0) as a model substrate:

7 FAD + 7 NAD+ + 7 CoASH + 7 H2O + H(CH2CH2)7CH2CO-SCoA --> 8 CH3CO-SCoA + 7 FADH2 + 7 NADH + 7 H+

Fate of acetyl CoA

Oxidation by the citric acid cycle to CO2 and H2O. In liver only, acetyl CoA may be used for ketone body synthesis.

Fate of the FADH2 and NADH + H+

FADH2 and NADH + H+ are oxidized by the mitochondrial electron transport system, yielding ATP

Four enzymes and reactions

There are four individual reactions of beta-oxidation, each catalyzed by a separate enzyme.

Dehydrogenation between the alpha and beta carbons (C2 and C3) in a FAD-linked reaction. Hydration of the double bond by enoyl CoA hydratase. A second dehydrogenation in a NAD-linked reaction. Thiolytic cleavage of the thioester by beta-ketoacyl CoA thiolase.

This sequence of four steps is repeated until the fatty acyl chain is completely degraded to acetyl CoA.

Four enzymes and reactions: Dehydrogenation

Dehydrogenation occurs between the alpha and beta carbons (C2 and C3) in a FAD-linked reaction catalyzed by acyl CoA dehydrogenase. The oxidation power of FAD is required to oxidize the alkyl chain, much as it is in the succinate dehydrogenase reaction of the tricarboxylic acid cycle. The product contains a trans- double bond. Involvement of the beta-carbon in this and subsequent steps gives the pathway its name.

There are three fatty acyl CoA dehydrogenases. Each is specific for a different acyl chain length, so different enzymes are involved in different stages of beta-oxidation.

Long chain fatty acyl CoA dehydrogenase (LCAD) acts on chains greater than C12. Medium chain fatty acyl CoA dehydrogenase (MCAD) acts on chains of C6 to C12. Short chain fatty acyl CoA dehydrogenase (SCAD) acts on chains of C4 to C6.

MCAD deficiency is thought to be one of the most common inborn errors of metabolism.

Four enzymes and reactions: Hydration

Hydration of the double bond is catalyzed by enoyl CoA hydratase. The product is an L-3-hydroxyacyl CoA.

Four enzymes and reactions: 2nd dehydrogenation

A second dehydrogenation, of the alcohol, occurs in a NAD-linked reaction catalyzed by beta-hydroxyacyl CoA dehydrogenase. The product is a ketone.

Four enzymes and reactions: Thiolytic cleavage

Thiolytic cleavage of the thioester is catalyzed by beta-ketoacyl CoA thiolase.

Reaction products: The products are acetyl CoA and a long chain fatty acyl CoA that is two carbons shorter than the original fatty acyl CoA.

The shortened fatty acyl group is now ready for another round of beta-oxidation. After the fatty acyl CoA has been reduced to acetyl or propionyl CoA, beta-oxidation is complete.

Regulation: This reaction is inhibited by high concentrations of acetyl CoA.

Beta-oxidation is regulated as a whole primarily by fatty acid availability; once fatty acids are in the mitochondria they are oxidized as long as there is adequate NAD+ and CoA.

Complete beta-oxidation of palmitoyl CoA

Note: this movie file (480K) requires the Shockwave plug-in to be viewed.

Complete beta-oxidation of palmitoyl CoA:

7 FAD + 7 NAD+ + 7 CoASH + 7 H2O + H(CH2CH2)7CH2CO-SCoA --> 8 CH3CO-SCoA + 7 FADH2 + 7 NADH + 7 H+

Additional Enzymes

Additional enzymes are needed for complete oxidation of unsaturated and odd-carbon fatty acids.

The action of enoyl CoA isomerase may be required. A system is needed to generate the trans- double bond required in beta-oxidation in place of the

cis- bond which occurs naturally in fatty acids. The three-carbon propionyl CoA residue from beta-oxidation of odd-chain fatty acids is

metabolized with special enzymes.

Additional Enzymes: Enoyl CoA

The action of enoyl CoA isomerase is required to handle double bonds at odd-numbered carbons because beta-oxidation generates or requires pre-existing double bonds at even-numbered carbons.

If there is a double bond at an odd-numbered carbon (e.g., 18:1 9), the action of enoyl CoA isomerase is required to move the naturally occurring cis- bond and convert it to the trans- bond used in beta-oxidation.

The product, with a trans- double bond, is a substrate for enoyl CoA hydratase, the second enzyme of beta-oxidation. Additional Enzymes: trans- vs cis

Generating a trans- instead of a cis- double bond.

If there is also a double bond at an even-numbered carbon (e.g., the second double bond in 18:2 9,12), the problem is to generate a trans- double bond instead of a cis-. This occurs in an indirect

manner. Both activities occur in the mitochondrial matrix.

FIRST: Three cycles of beta-oxidation occur normally. Beta-oxidation then continues as expected in the presence of the 9 double bond through the fourth cycle, generating a trans- double bond at the 2-position. Enoyl CoA isomerase is involved, as described previously. The fourth cycle completes, and the fifth cycle then begins normally, but proceeds only through the acyl CoA dehydrogenase step.

SECOND: 2,4-dienoyl CoA reductase reduces the compound, leaving one trans- double bond, but in the wrong position. NADPH + H+ is required.

The product is a substrate for enoyl isomerase, the same enzyme used for cis- double bonds at odd-numbered carbons. It moves the double bond from the 3 to the 2 position.

Beta-oxidation now proceeds normally.

Additional Enzymes: Propionyl CoA

Handling the three-carbon propionyl CoA

Fatty acids with an odd number of carbons in their chains require a means of handling the three-carbon propionyl CoA that is the final fragment produced by beta-oxidation of such a chain:

The first step is carboxylation by the biotin-dependent propionyl CoA carboxylase in an ATP-requiring reaction.

The D- isomer, which is the product, is then converted to the L- isomer by methylmalonyl CoA racemase.

In the final step, the L- isomer is converted to succinyl CoA by methylmalonyl CoA mutase.

Succinyl CoA can then be metabolized through the tricarboxylic acid cycle.

Summary

Complete Oxidation of an Odd-Chain Fatty Acid -- Summary

This diagram shows production of propionyl CoA from an odd-chain fatty acid and the subsequent conversion of propionyl CoA to succinyl CoA, which can be metabolized through the citric (tricarboxylic) acid cycle.

X. Synthesis and Utilization of Ketone Bodies

OverviewSynthesis from acetyl CoAStep 1Step 2Step 3AcetoacetateAcetoneExtrahepatic tissues

Overview

These are the compounds known as ketone bodies. Notice that beta-hydroxybutyrate is not chemically a ketone. It is considered to be physiologically equivalent to one because it and acetoacetate are readily interconverted in the body.

Synthesis from acetyl CoA

Ketone bodies are synthesized from acetyl CoA.

Ketone body synthesis from acetyl CoA occurs in hepatic mitochondria. First, acetoacetate is produced in a three-step process. Acetoacetate can be reduced to beta-hydroxybutyrate. Acetone also arises in small amounts as a biologically inert side product.

Ketone body production is regulated primarily by availability of acetyl CoA. If mobilization of fatty acids from adipose tissue is high, hepatic beta-oxidation will occur at a high rate, and so will synthesis of ketone bodies from the resulting acetyl CoA. The rate of ketone body production increases in starvation.

Synthesis from acetyl CoA: Step 1

The first step is formation of acetoacetyl CoA in a reversal of the thiolase step of beta-oxidation.

Synthesis from acetyl CoA: Step 2

In the second step, a third molecule of acetyl CoA condenses with the acetoacetyl CoA, forming 3-hydroxy-3-methylglutaryl CoA (HMG CoA) in a reaction catalyzed by HMG CoA synthase.

Synthesis from acetyl CoA: Step 3

In the third step HMG CoA is cleaved to yield acetoacetate (a ketone body) in a reaction catalyzed by HMG CoA lyase (HMG CoA cleavage enzyme). One molecule of acetyl CoA is also produced.

Synthesis from acetyl CoA: Acetoacetate

Acetoacetate can be reduced.

Subsequently acetoacetate can be reduced to beta-hydroxybutyrate by beta-hydroxybutyrate dehydrogenase in a NADH-requiring reaction. The extent of this reaction depends on the state of the NAD pool of the cell; when it is highly reduced, most or all of the ketones can be in the form of beta-hydroxybutyrate.

Near-total reduction of acetoacetate to beta-hydroxybutyrate can occur in severe ethanol toxicity.

Synthesis from acetyl CoA: Acetone

Some acetoacetate spontaneously decarboxylates to yield acetone.

Some acetoacetate spontaneously decarboxylates to yield acetone. The odor of acetone can be smelled on the breath of individuals with severe ketosis.

Extrahepatic tissues

Ketone bodies are utilized exclusively by extrahepatic tissues; heart and skeletal muscle use them particularly effectively.

If the ketone is beta-hydroxybutyrate, the first step must be reoxidation to acetoacetate, in a reversal of the reaction described previously.

Acetoacetate is activated by transfer of CoA from succinyl CoA. Acetoacetate is activated by transfer of CoA from succinyl CoA in a reaction catalyzed by succinyl CoA: 3-ketoacid CoA transferase.

The enzyme catalyzing this reaction is absent from liver; hence liver, which synthesizes ketone bodies, cannot use them. This places liver in the role of being a net producer of ketones.

The resulting acetoacetyl CoA can be cleaved by thiolase to form two molecules of acetyl CoA, which can then be oxidized by the tricarboxylic acid cycle.

XI. Overall Regulation of Fatty Acid Metabolism

Overview

SynthesisOxidation

OverviewLike all metabolic processes, fatty acid metabolism is regulated to prevent inappropriate simultaneous

synthesis and degradation.

Overview: Synthesis

Substrate availability: availability of acetyl groups in the cytoplasm is regulated by the activity of the citrate-malate antiport. Its activity is decreased by palmitoyl CoA. The mitochondrial concentration of citrate also affects transport.

Acetyl CoA carboxylase is a key enzyme of fatty acid synthesis.o It is activated allosterically by citrate and covalently by phosphorylation. o It is inhibited allosterically by palmitoyl CoA and covalently by dephosphorylation.

Overview: Oxidation

Oxidation is regulated at several levels, but primarily by substrate availability, which in turn is controlled hormonally.

Hormone sensitive lipase in adipose tissue is activated by phosphorylation (glucagon). Its activity is low when insulin levels are high.

High levels of malonyl CoA allosterically inhibit CAT-I. This prevents beta-oxidation during fatty acid synthesis.

CoA must be available for beta-oxidation to proceed, since it is a substrate for the thiolase reaction.

Biochimie

Date generale despre moleculele biologice; zaharide (monozaharide, dizaharide, polizaharide) definitie,

exemple, formule; proteine: structurile primara, secundara, tertiara si cuaternara, cu exemple; lipide:

trigliceride si fosfolipide; cromatografie: definitie, principiul metodei, tipuri de cromatografie.

Autor: www.biologymad.com

Life on Earth evolved in the water, and all life still depends on water. At least 80% of the mass of living

organisms is water, and almost all the chemical reactions of life take place in aqueous solution. The other

chemicals that make up living things are mostly organic macromolecules belonging to the four groups

proteins, nucleic acids, carbohydrates or lipids. These macromolecules are made up from specific

monomers as shown in the table below. Between them these four groups make up 93% of the dry mass

of living organisms, the remaining 7% comprising small organic molecules (like vitamins) and inorganic

ions.

Group name monomers polymers % dry mass

Proteins amino acids polypeptides 50

nucleic acids nucleotides polynucleotides 18

carbohydrates monosaccharides polysaccharides 15

     

Group name components largest unit % dry mass

lipids fatty acids + glycerol Triglycerides 10

 The first part of this unit is about each of these groups. We'll look at each of these groups in detail,

except nucleic acids, which are studied in module 2.

 

Water (additional information for your own interest)[back to top]

Water molecules are charged, with the oxygen atom being slightly negative (-) and the hydrogen atoms

being slightly positive (+). These opposite charges attract each other, forming hydrogen bonds. These

are weak, long distance bonds that are very common and very important in biology.

Water has a number of important properties essential for life. Many of the properties below are due to the

hydrogen bonds in water:

Solvent. Because it is charged, water is a very good solvent. Charged or polar molecules such

as salts, sugars, amino acids dissolve readily in water and so are called hydrophilic ("water

loving"). Uncharged or non-polar molecules such as lipids do not dissolve so well in water and are

called hydrophobic ("water hating").

Specific heat capacity. Water has a specific heat capacity of 4.2 J g-1 °C-1, which means that it

takes 4.2 joules of energy to heat 1 g of water by 1°C. This is unusually high and it means that

water does not change temperature very easily. This minimises fluctuations in temperature inside

cells, and it also means that sea temperature is remarkably constant.

Latent heat of vaporisation. Water requires a lot of energy to change state from a liquid into a

gas, and this is made use of as a cooling mechanism in animals (sweating and panting) and

plants (transpiration). As water evaporates it extracts heat from around it, cooling the organism.

 Latent heat of fusion. Water also requires a lot of heat to change state from a solid to a liquid,

and must loose a lot of heat to change state from a liquid to a solid. This means it is difficult to

freeze water, so ice crystals are less likely to form inside cells.

Density. Water is unique in that the solid state (ice) is less dense that the liquid state, so ice

floats on water. As the air temperature cools, bodies of water freeze from the surface, forming a

layer of ice with liquid water underneath. This allows aquatic ecosystems to exist even in sub-

zero temperatures.

Cohesion. Water molecules "stick together" due to their hydrogen bonds, so water has high

cohesion. This explains why long columns of water can be sucked up tall trees by transpiration

without breaking. It also explains surface tension, which allows small animals to walk on water.

Ionisation. When many salts dissolve in water they ionise into discrete positive and negative ions

(e.g. NaCl   Na+ + Cl-). Many important biological molecules are weak acids, which also ionise in

solution (e.g. acetic acid   acetate- + H+). The names of the acid and ionised forms (acetic acid

and acetate in this example) are often used loosely and interchangeably, which can cause

confusion. You will come across many examples of two names referring to the same substance,

e.g.: phosphoric acid and phosphate, lactic acid and lactate, citric acid and citrate, pyruvic acid

and pyruvate, aspartic acid and aspartate, etc. The ionised form is the one found in living cells.

pH. Water itself is partly ionised (H2O    H+ + OH- ), so it is a source of protons (H+ ions), and

indeed many biochemical reactions are sensitive to pH (-log[H+]). Pure water cannot buffer

changes in H+ concentration, so is not a buffer and can easily be any pH, but the cytoplasms and

tissue fluids of living organisms are usually well buffered at about neutral pH (pH 7-8).

 

Carbohydrates  [back to top]

Carbohydrates contain only the elements carbon, hydrogen and oxygen. The group includes monomers, dimers and polymers, as shown in this diagram:

Monosaccharides (simple sugars)  [back to top]

These all have the formula (CH2O)n, where n can be 3-7. The most common and important

monosaccharide is glucose, which is a six-carbon or hexose sugar, so has the formula C6H12O6. Its

structure is:

-glucose (used to make starch and glycogen) or more simply

-glucose (used to make cellulose)

Glucose forms a six-sided ring, although in three-dimensions it forms a structure that looks a bit like a

chair. The six carbon atoms are numbered as shown, so we can refer to individual carbon atoms in the

structure. In animals glucose is the main transport sugar in the blood, and its concentration in the blood is

carefully controlled. There are many isomers of glucose, with the same chemical formula (C6H12O6), but

different structural formulae. These isomers include fructose and galactose.

Common five-carbon, or pentose sugars (where n = 5, C5H10O5) include ribose and deoxyribose (found in

nucleic acids and ATP) and ribulose (which occurs in photosynthesis).

Disaccharides (double sugars)  [back to top]

Disaccharides are formed when two monosaccharides are joined together by a glycosidic bond. The

reaction involves the formation of a molecule of water (H2O):

 

This shows two glucose molecules joining together to form the disaccharide maltose. Because this bond

is between carbon 1 of one molecule and carbon 4 of the other molecule it is called a 1-4 glycosidic bond.

Bonds between other carbon atoms are possible, leading to different shapes, and branched chains.

This kind of reaction, where H2O is formed, is called a condensation reaction. The reverse process, when

bonds are broken by the addition of water (e.g. in digestion), is called a hydrolysis reaction.

In

general:

 polymerisation reactions are condensations

breakdown reactions are hydrolyses

 There are three common disaccharides:

Maltose (or malt sugar) is glucose 1-4 glucose. It is formed on digestion of starch by amylase,

because this enzyme breaks starch down into two-glucose units. Brewing beer starts with malt,

which is a maltose solution made from germinated barley. Maltose is the structure shown above.

Sucrose (or cane sugar) is glucose 1-2 fructose. It is common in plants because it is less reactive

than glucose, and it is their main transport sugar. It is the common table sugar that you put in

your tea.

Lactose (or milk sugar) is galactose 1-4 glucose. It is found only in mammalian milk, and is the

main source of energy for infant mammals.

Polysaccharides  [back to top]

Polysaccharides are long chains of many monosaccharides joined together by glycosidic bonds. There

are three important polysaccharides:

Starch is the plant storage polysaccharide. It is insoluble and forms starch granules inside many

plant cells. Being insoluble means starch does not change the water potential of cells, so does

not cause the cells to take up water by osmosis (more on osmosis later). It is not a pure

substance, but is a mixture of amylose and amylopectin.

Amylose is simply poly-(1-4) glucose, so is a straight

chain. In fact the chain is floppy, and it tends to coil up

into a helix.

Amylopectin is poly(1-4) glucose with about 4% (1-6)

branches. This gives it a more open molecular

structure than amylose. Because it has more ends, it

can be broken more quickly than amylose by amylase

enzymes.

Both amylose and amylopectin are broken down by the enzyme amylase into maltose, though at different rates.

Glycogen is similar in structure to amylopectin. It

is poly (1-4) glucose with 9% (1-6) branches. It is

made by animals as their storage polysaccharide,

and is found mainly in muscle and liver. Because

it is so highly branched, it can be mobilised

(broken down to glucose for energy) very quickly.

 Cellulose is only found in plants, where it is the main component of cell walls. It is poly (1-4)

glucose, but with a different isomer of glucose. Starch and glycogen contain a-glucose, in which

the hydroxyl group on carbon 1 sticks down from the ring, while cellulose contains b-glucose, in

which the hydroxyl group on carbon 1 sticks up. This means that in a chain alternate glucose

molecules are inverted.

This apparently tiny difference makes a huge difference in structure and properties. While the 1-4

glucose polymer in starch coils up to form granules, the 14 glucose polymer in cellulose forms straight

chains. Hundreds of these chains are linked together by hydrogen bonds to form cellulose microfibrils.

These microfibrils are very strong and rigid, and give strength to plant cells, and therefore to young plants

and also to materials such as paper, cotton and sellotape.

The b-glycosidic bond cannot be broken by amylase, but requires a specific cellulase enzyme. The only

organisms that possess a cellulase enzyme are bacteria, so herbivorous animals, like cows and termites

whose diet is mainly cellulose, have mutualistic bacteria in their guts so that they can digest cellulose.

Humans cannot digest cellulose, and it is referred to as fibre.

Other polysaccharides that you may come across include:

Chitin (poly glucose amine), found in fungal cell walls and the exoskeletons of insects.

Pectin (poly galactose uronate), found in plant cell walls.

Agar (poly galactose sulphate), found in algae and used to make agar plates.

Murein (a sugar-peptide polymer), found in bacterial cell walls.

Lignin (a complex polymer), found in the walls of xylem cells, is the main component of wood.

Proteins  [back to top]

Proteins are the most complex and most diverse group of biological compounds. They have an

astonishing range of different functions, as this list shows.

structure                e.g. collagen (bone, cartilage, tendon), keratin (hair), actin (muscle)

enzymes               e.g. amylase, pepsin, catalase, etc (>10,000 others)

transport                e.g. haemoglobin (oxygen), transferrin (iron)

pumps                   e.g. Na+K+ pump in cell membranes

motors                  e.g. myosin (muscle), kinesin (cilia)

hormones              e.g. insulin, glucagon

receptors               e.g. rhodopsin (light receptor in retina)

antibodies              e.g. immunoglobulins

storage                  e.g. albumins in eggs and blood, caesin in milk

blood clotting         e.g. thrombin, fibrin

lubrication              e.g. glycoproteins in synovial fluid

toxins                    e.g. diphtheria toxin

antifreeze              e.g. glycoproteins in arctic flea

and many more!

Proteins are made of amino acids. Amino acids are

made of the five elements C H O N S. The general

structure of an amino acid molecule is shown on the

right. There is a central carbon atom (called the

"alpha carbon"), with four different chemical groups

attached to it:

a hydrogen atom

a basic amino group

an acidic carboxyl group

a variable "R" group (or side chain)

Amino acids are so-called because they have both amino groups and acid groups, which have opposite

charges. At neutral pH (found in most living organisms), the groups are ionised as shown above, so there

is a positive charge at one end of the molecule and a negative charge at the other end. The overall net

charge on the molecule is therefore zero. A molecule like this, with both positive and negative charges is

called a zwitterion. The charge on the amino acid changes with pH:

low pH (acid) neutral pH high pH (alkali)

charge = +1 charge = 0 charge = -1

It is these changes in charge with pH that explain the effect of pH on enzymes. A solid, crystallised amino

acid has the uncharged structure (bwlow) , but this form never exists in solution, and therefore doesn't

exist in living things 

(although it is the form usually given in textbooks).

 

There are 20 different R groups, and so 20 different amino acids. Since each R group is slightly different,

each amino acid has different properties, and this in turn means that proteins can have a wide range of

properties. The following table shows the 20 different R groups, grouped by property, which gives an idea

of the range of properties. You do not need to learn these, but it is interesting to see the different

structures, and you should be familiar with the amino acid names. You may already have heard of some,

such as the food additive monosodium glutamate, which is simply the sodium salt of the amino acid

glutamate. Be careful not to confuse the names of amino acids with those of bases in DNA, such as

cysteine (amino acid) and cytosine (base), threonine (amino acid) and thymine (base). There are 3-letter

and 1-letter abbreviations for each amino acid.

The Twenty Amino Acid  R-Groups   Simple R groups   Basic R groups

Glycine

Gly  G

Lysine

Lys  K

Alanine

Ala  A

Arginine

Arg  R

Valine

Val  V

Histidine

His  H

Leucine

Leu  L

Asparagine

Asn  N

Isoleucine

Ile  I

Glutamine

Gln  Q

  Hydroxyl R groups   Acidic R groups

Serine

Ser  S

Aspartate

Asp  D

Threonine

Thr  T

Glutamate

Glu  E

  Sulphur R groups   Ringed R groups

Cysteine

Cys  C

Phenylalanine

Phe  F

Methionine

Met  M

Tyrosine

Tyr  Y

  Cyclic R group    

Proline

Pro  P

Tryptophan

Trp  W

 

Polypeptides  [back to top]

Amino acids are joined together by peptide bonds. The reaction involves the formation of a molecule of

water in another condensation polymerisation reaction:

When two amino acids join together a dipeptide is formed. Three amino acids form a tripeptide. Many

amino acids form a polypeptide. e.g.:

+NH3-Gly — Pro — His — Leu — Tyr — Ser — Trp — Asp — Lys — Cys-COO-

 In a polypeptide there is always one end with a free amino (NH3) group, called the N-terminus, and one

end with a free carboxyl (CO2) group, called the C-terminus.

In a protein the polypeptide chain may be hundreds of amino acids long. Amino acid polymerisation to

form polypeptides is part of protein synthesis. It takes place in ribosomes, and is special because it

requires an RNA template. The sequence of amino acids in a polypeptide chain is determined by the

sequence of the genetic code in DNA. Protein synthesis it studied in detail in module 2.

Protein Structure  [back to top]

Polypeptides are just a string of amino acids, but they fold up to form the complex and well-defined three-

dimensional structure of working proteins. To help to understand protein structure, it is broken down into

four levels:

1.    Primary Structure

This is just the sequence of amino acids in the polypeptide chain, so is not really a structure at all.

However, the primary structure does determine the rest of the protein structure. Finding the primary

structure of a protein is called protein sequencing, and the first protein to be sequenced was the

protein hormone insulin, by the Cambridge biochemist Fredrick Sanger, for which work he got the

Nobel prize in 1958.

2.    Secondary Structure

This is the most basic level of protein folding, and consists of a few

basic motifs that are found in all proteins. The secondary structure is

held together by hydrogen bonds between the carboxyl groups and

the amino groups in the polypeptide backbone. The two most

common secondary structure motifs are the -helix and the -sheet .

The -helix. The polypeptide chain is

wound round to form a helix. It is held

together by hydrogen bonds running

parallel with the long helical axis. There are

so many hydrogen bonds that this is a very

stable and strong structure. Do not confuse

the a-helix of proteins with the famous

double helix of DNA. Helices are common

structures throughout biology.

 

 

The -sheet. The polypeptide chain zig-

zags back and forward forming a sheet of

antiparallel strands. Once again it is held

together by hydrogen bonds.

The -helix and the -sheet were discovered by Linus Pauling, for which work he got the Nobel prize

in 1954. There are a number of other secondary structure motifs such as the -bend, the triple helix

(only found in collagen), and the random coil.

3.    Tertiary Structure

This is the compact globular structure formed by the folding up of a whole polypeptide chain. Every

protein has a unique tertiary structure, which is responsible for its properties and function. For

example the shape of the active site in an enzyme is due to its tertiary structure. The tertiary

structure is held together by bonds between the R groups of the amino acids in the protein, and so

depends on what the sequence of amino acids is. There are three kinds of bonds involved:

hydrogen bonds , which are weak.

ionic bonds between R-groups with positive or negative charges, which are quite strong.

sulphur bridges - covalent S-S bonds between two cysteine amino acids, which are strong.

So the secondary structure is due to backbone interactions and is thus largely independent of

primary sequence, while tertiary structure is due to side chain interactions and thus depends on the

amino acid sequence.

4.    Quaternary Structure

This structure is found in proteins containing more than one polypeptide chain, and simply means

how the different polypeptide chains are arranged together. The individual polypeptide chains are

usually globular, but can arrange themselves into a variety of quaternary shapes. e.g.:

Haemoglobin, the oxygen-carrying protein in red

blood cells, consists of four globular subunits

arranged in a tetrahedral (pyramid) structure.

Each subunit contains one iron atom and can

bind one molecule of oxygen.

Immunoglobulins, the proteins that make

antibodies, comprise four polypeptide chains

arranged in a Y-shape. The chains are held

together by sulphur bridges. This shape allows

antibodies to link antigens together, causing

them to clump.

Actin, one of the proteins found in muscles,

consists of many globular subunits arranged in a

double helix to form long filaments.

Tubulin is a globular protein that polymerises to

form hollow tubes called microtubules. These

form part of the cytoskeleton, and make cilia

and flagella move.

These four structures are not real stages in the formation of a protein, but are simply a convenient

classification that scientists invented to help them to understand proteins. In fact proteins fold into all

these structures at the same time, as they are synthesised.

The final three-dimensional shape of a protein can be classified as globular or fibrous.

globular structure  fibrous (or filamentous) structure

The vast majority of proteins are globular, including enzymes, membrane proteins, receptors, storage

proteins, etc. Fibrous proteins look like ropes and tend to have structural roles such as collagen (bone),

keratin (hair), tubulin (cytoskeleton) and actin (muscle). They are usually composed of many polypeptide

chains. A few proteins have both structures: the muscle protein myosin has a long fibrous tail and a

globular head, which acts as an enzyme.

This diagram shows a molecule of the enzyme

dihydrofolate reductase, which comprises a

single polypeptide chain. It has been drawn to

highlight the different secondary structures.

This diagram shows part of a molecule of

collagen, which is found in bone and cartilage.

It has a unique, very strong triple-helix

structure.

 

 

Lipids  [back to top]

Lipids are a mixed group of hydrophobic compounds composed of the elements carbon, hydrogen and

oxygen.

Triglycerides  [back to top]

Triglycerides are commonly called fats or oils. They are made of glycerol and fatty acids.

Glycerol

is a

small, 3-

carbon

molecul

e with

three

alcohol

groups.

Fatty acids are long molecules with a

polar, hydrophilic end and a non-

polar, hydrophobic "tail". The

hydrocarbon chain can be from 14 to

22 CH2 units long, but it is always an

even number because of the way

fatty acids are made. The hydrocarbon chain is sometimes called an R group, so the formula of a fatty

acid can be written as R-COO-.

If there are no C=C double bonds in the hydrocarbon chain, then it is a saturated fatty acid (i.e.

saturated with hydrogen). These fatty acids form straight chains, and have a high melting point.

If there are C=C double bonds in the hydrocarbon chain, then it is an unsaturated fatty acid (i.e.

unsaturated with hydrogen). These fatty acids form bent chains, and have a low melting point. Fatty acids

with more than one double bond are called poly-unsaturated fatty acids (PUFAs).

One molecule of glycerol joins togther with three fatty acid molecules to form a triglyceride molecule, in

another condensation polymerisation reaction:

Triglycerides are insoluble in water. They are used for storage, insulation and protection in fatty tissue (or

adipose tissue) found under the skin (sub-cutaneous) or surrounding organs. They yield more energy per

unit mass than other compounds so are good for energy storage. Carbohydrates can be mobilised more

quickly, and glycogen is stored in muscles and liver for immediate energy requirements.

Triglycerides containing saturated fatty acids have a high melting point and tend to be found in

warm-blooded animals. At room temperature thay are solids (fats), e.g. butter, lard.

Triglycerides containing unsaturated fatty acids have a low melting point and tend to be found in

cold-blooded animals and plants. At room temperature they are liquids (oils), e.g. fish oil,

vegetable oils.

Phospholipids  [back to top]

Phospholipids have a similar structure to triglycerides, but with a phosphate group in place of one fatty

acid chain. There may also be other groups attached to the phosphate. Phospholipids have a polar

hydrophilic "head" (the negatively-charged phosphate group) and two non-polar hydrophobic "tails" (the

fatty acid chains). This mixture of properties is fundamental to biology, for phospholipids are the main

components of cell membranes.

When mixed with water, phospholipids form

droplet spheres with the hydrophilic heads

facting the water and the hydrophobic tails facing

eachother. This is called a micelle.

 

Alternatively, they may form a double-layered

phospholipid bilayer. This traps a compartment

of water in the middle separated from the

external water by the hydrophobic sphere. This

naturally-occurring structure is called a liposome,

and is similar to a membrane surrounding a cell.

Waxes

Waxes are formed from fatty acids and long-chain alcohols. They are commonly found wherever

waterproofing is needed, such as in leaf cuticles, insect exoskeletons, birds' feathers and mammals' fur.

Steroids

Steroids are small hydrophobic molecules found mainly in animals. They include:

cholesterol , which is found in animals cell membranes to increase stiffness

bile salts , which help to emulsify dietary fats

steroid hormones such as testosterone, oestrogen, progesterone and cortisol

vitamin D, which aids Ca2+ uptake by bones.

Terpenes

Terpenes are small hydrophobic molecules found mainly in plants. They include vitamin A, carotene and

plant oils such as geraniol, camphor and menthol.

  Chromatography  [back to top]

Chromatography is used to separate pure substances from a mixture of substances, such as a cell extract. It is based on different substances having different solubilities in different solvents. A simple and common form of chromatography uses filter paper.

1.     Pour some solvent into a chromatography tank and seal it, so the atmosphere is saturated with

solvent vapour. Different solvents are suitable for different tasks, but they are usually mixtures of

water with organic liquids such as ethanol or propanone.

2.     Place a drop of the mixture to be separated onto a sheet of chromatography paper near one end.

This is the origin of the chromatogram. The spot should be small but concentrated. Repeat for any

other mixtures. Label the spots with pencil, as ink may dissolve.

3.     Place the chromatography sheet into the tank so that the origin is just above the level of solvent, and

leave for several hours. The solvent will rise up the paper by capillary action carrying the contents of

the mixture with it. Any solutes dissolved in the solvent will be partitioned between the organic solvent

(the moving phase) and the water, which is held by the paper (the stationary phase). The more

soluble a solute is in the solvent the further up the paper it will move.

4.     When the solvent has nearly reached the top of the paper, the paper is removed and the position of

the solvent front marked. The chromatogram may need to be developed to make the spots visible.

For example amino acids stain purple with ninhydrin.

5.    The chromatogram can be analysed by measuring the distance travelled by the solvent front, and the

distance from the origin to the centre of each spot. This is used to calculate the Rf (relative front)

value for each spot:

Rf = distance moved by spot

distance moved by solvent

 An Rf value is characteristic of a particular solute in a particular solvent. It can be used to identify

components of a mixture by comparing to tables of known Rf  values.

Sometimes chromatography with a single solvent is not enough to separate all the constituents of a

mixture. In this case the separation can be improved by two-dimensional chromatography, where the

chromatography paper is turned through 90° and run a second time in a second solvent. Solutes that

didn't separate in one solvent will separate in another because they have different solubilities.

There are many different types of chromatography.

Paper chromatography is the simplest, but does not always give very clean separation.

Thin layer chromatography (tlc) uses a thin layer of cellulose or silica coated onto a plastic or

glass sheet. This is more expensive, but gives much better and more reliable separation.

Column chromatography uses a glass column filled with a cellulose slurry. Large samples can be

pumped through the column and the separated fractions can be collected for further experiments,

so this is preparative chromatography as opposed to analytical chromatography.

High performance liquid chromatography (HPLC) is an improved form of column chromatography

that delivers excellent separation very quickly.

Electrophoresis uses an electric current to separate molecules on the basis of charge. It can also

be used to separate on the basis of molecular size, and as such is used in DNA sequencing.

 

Biochemical Tests  [back to top]

These five tests identify the main biologically important chemical compounds. For each test take a small

amount of the substance to test, and shake it in water in a test tube. If the sample is a piece of food, then

grind it with some water in a pestle and mortar to break up the cells and release the cell contents. Many of

these compounds are insoluble, but the tests work just as well on a fine suspension.

Starch (iodine test). To approximately 2 cm³ of test solution add two drops of iodine/potassium

iodide solution. A blue-black colour indicates the presence of starch as a starch-polyiodide

complex is formed. Starch is only slightly soluble in water, but the test works well in a suspension

or as a solid.

Reducing Sugars (Benedict's test). All monosaccharides and most disaccharides (except

sucrose) will reduce copper (II) sulphate, producing a precipitate of copper (I) oxide on heating,

so they are called reducing sugars. Benedict’s reagent is an aqueous solution of copper (II)

sulphate, sodium carbonate and sodium citrate. To approximately 2 cm³ of test solution add an

equal quantity of Benedict’s reagent. Shake, and heat for a few minutes at 95°C in a water bath.

A precipitate indicates reducing sugar. The colour and density of the precipitate gives an

indication of the amount of reducing sugar present, so this test is semi-quantitative. The original

pale blue colour means no reducing sugar, a green precipitate means relatively little sugar; a

brown or red precipitate means progressively more sugar is present.

Non-reducing Sugars (Benedict's test). Sucrose is called a non-reducing sugar because it does

not reduce copper sulphate, so there is no direct test for sucrose. However, if it is first hydrolysed

(broken down) to its constituent monosaccharides (glucose and fructose), it will then give a

positive Benedict's test. So sucrose is the only sugar that will give a negative Benedict's test

before hydrolysis and a positive test afterwards. First test a sample for reducing sugars, to see if

there are any present before hydrolysis. Then, using a separate sample, boil the test solution with

dilute hydrochloric acid for a few minutes to hydrolyse the glycosidic bond. Neutralise the solution

by gently adding small amounts of solid sodium hydrogen carbonate until it stops fizzing, then test

as before for reducing sugars.

Lipids (emulsion test). Lipids do not dissolve in water, but do dissolve in ethanol. This

characteristic is used in the emulsion test. Do not start by dissolving the sample in water, but

instead shake some of the test sample with about 4 cm³ of ethanol. Decant the liquid into a test

tube of water, leaving any undissolved substances behind. If there are lipids dissolved in the

ethanol, they will precipitate in the water, forming a cloudy white emulsion. The test can be

improved by adding the dye Sudan III, which stains lipids red.

Protein (biuret test). To about 2 cm³ of test solution add an equal volume of biuret solution, down

the side of the test tube. A blue ring forms at the surface of the solution, which disappears on

shaking, and the solution turns lilac-purple, indicating protein. The colour is due to a complex

between nitrogen atoms in the peptide chain and Cu2+ ions, so this is really a test for peptide

bonds.

Cai metaboliceMetabolismul lipidelor (activarea acizilor grasi, beta-oxidarea acizilor grasi biosinteza colesterolului; metabolismul zaharidelor; metabolismul aminoacizilor; metabolismul energetic.

Aici veti gasi si structurile 3D ale unor coenzime (ATP, CoA, FAD, NAD+, NADP+Autor: Karl J. Miller B.S.

Monozaharide, carbohidrati, glucideStructura chimica a tetrozelor, pentozelor, hexozelor si heptozelor. Izomeri, stereochimie, polialcooli, aminozaharide, acizi uronici.Autor: ScientificPsychic.com

1 | 2 | 3 | Next > Carbohydrates - Chemical Structure

Carbohydrates consist of the elements carbon (C), hydrogen (H) and oxygen (O) with a ratio of hydrogen twice that of carbon and oxygen. Carbohydrates include sugars, starches, cellulose and many other compounds found in living organisms. In their basic form, carbohydrates are simple sugars or monosaccharides. These simple sugars can combine with each other to form more complex carbohydrates. The combination of two simple sugars is a disaccharide. Carbohydrates consisting of two to ten simple sugars are called oligosaccharides, and those with a larger number are called polysaccharides.

Sugar and Cotton are Carbohydrates

Sugars

Sugars are white crystalline carbohydrates that are soluble in water and generally have a sweet taste.

Monosaccharides are simple sugars

Monosaccharide classifications based on the number of carbons

Number of

Carbons

Category Name

Examples

4 Tetrose Erythrose, Threose

5 Pentose Arabinose, Ribose, Ribulose, Xylose, Xylulose, Lyxose

6 HexoseAllose, Altrose, Fructose, Galactose, Glucose, Gulose, Idose, Mannose, Sorbose, Talose, Tagatose

7 Heptose Sedoheptulose

Many saccharide structures differ only in the orientation of the hydroxyl groups (-OH). This slight structural difference makes a big difference in the biochemical properties, organoleptic properties (e.g., taste), and in the physical properties such as melting point and Specific Rotation (how polarized light is distorted). A chain-form monosaccharide that has a carbonyl group (C=O) on an end carbon forming an aldehyde group (-CHO) is classified as an aldose. When the carbonyl group is on an inner atom forming a ketone, it is classified as a ketose.

Tetroses

D-Erythrose D-Threose

Pentoses

D-Ribose D-Arabinose D-Xylose D-Lyxose

The ring form of ribose is a component of ribonucleic acid (RNA).   Deoxyribose, which is missing an oxygen at position 2, is a component of deoxyribonucleic   acid   (DNA) . In nucleic acids, the hydroxyl group attached to carbon number 1 is replaced with nucleotide bases.

Ribose Deoxyribose

Hexoses

Hexoses, such as the ones illustrated here, have the molecular formula C6H12O6. German chemist Emil Fischer (1852-1919) identified the stereoisomers for these aldohexoses in 1894. He received the 1902 Nobel Prize for chemistry for his work. Any online degree programs in Chemistry or Master of Science in Pharmaceutical Chemistry will study his findings.

D-Allose D-Altrose D-Glucose D-Mannose

D-Gulose D-Idose D-Galactose D-Talose

Structures that have opposite configurations of a hydroxyl group at only one position, such as glucose and mannose, are called epimers. Glucose, also called dextrose, is the most widely distributed sugar in the plant and animal kingdoms and it is the sugar present in blood as "blood sugar". The chain form of glucose is a polyhydric aldehyde, meaning that it has multiple hydroxyl groups and an aldehyde group. Fructose, also called levulose or "fruit sugar", is shown here in the chain and ring forms. The relationship between the chain and the ring forms of the sugars is discussed below. Fructose and glucose are the main carbohydrate constituents of honey.

D-Tagatose(a ketose)

D-Fructose Fructose Galactose Mannose

HeptosesSedoheptulose has the same structure as fructose, but it has one extra carbon.

D-Sedoheptulose

Chain and Ring forms

Many simple sugars can exist in a chain form or a ring form, as illustrated by the hexoses above. The ring form is favored in aqueous solutions, and the mechanism of ring formation is similar for most sugars. The glucose ring form is created when the oxygen on carbon number 5 links with the carbon comprising the carbonyl group (carbon number 1) and transfers its hydrogen to the carbonyl oxygen to create a hydroxyl group. The rearrangement produces alpha   glucose when the hydroxyl group is on the opposite side of the -CH2OH group, or beta   glucose when the hydroxyl group is on the same side as the -CH2OH group. Isomers, such as these, which differ only in their configuration about their carbonyl carbon atom are called anomers. The little D in the name derives from the fact that natural glucose is dextrorotary, i.e., it rotates polarized light to the right, but it now denotes a specific configuration. Monosaccharides forming a five-sided

ring, like ribose, are called furanoses. Those forming six-sided rings, like glucose, are called pyranoses.

D-Glucose(an aldose)

α-D-Glucose β-D-Glucose Cyclation of Glucose

Stereochemistry

Saccharides with identical functional groups but with different spatial configurations have different chemical and biological properties. Stereochemisty is the study of the arrangement of atoms in three-dimensional space. Stereoisomers are compounds in which the atoms are linked in the same order but differ in their spatial arrangement. Compounds that are mirror images of each other but are not identical, comparable to left and right shoes, are called enantiomers. The following structures illustrate the difference between β-D-Glucose and β-L-Glucose. Identical molecules can be made to correspond to each other by flipping and rotating. However, enantiomers cannot be made to correspond to their mirror images by flipping and rotating. Glucose is sometimes illustrated as a "chair form" because it is a more accurate representation of the bond angles of the molecule. The "boat" form of glucose is unstable.

β-D-Glucose β-L-Glucose β-D-Glucose(chair form)

β-D-Glucose β-L-Glucoseβ-D-Glucose(boat form)

Sugar Alcohols, Amino Sugars, and Uronic Acids

Sugars may be modified by natural or laboratory processes into compounds that retain the basic configuration of saccharides, but have different functional groups. Sugar alcohols, also known as polyols, polyhydric alcohols, or polyalcohols, are the hydrogenated forms of the aldoses or ketoses. For example, glucitol, also known as sorbitol, has the same linear structure as the chain form of glucose, but the aldehyde (-CHO) group is replaced with a -CH2OH group. Other common sugar alcohols include the monosaccharides erythritol and xylitol and the disaccharides lactitol and maltitol. Sugar alcohols have about half the calories of sugars and are frequently used in low-calorie or "sugar-free" products.

Xylitol, which has the hydroxyl groups oriented like xylose, is a very common ingredient in "sugar-free" candies and gums because it is approximately as sweet as sucrose, but contains 40% less food energy. Although this sugar alcohol appears to be safe for humans, xylitol in relatively small doses can cause seizures, liver failure, and death in dogs.

Amino sugars or aminosaccharides replace a hydroxyl group with an amino (-NH2) group. Glucosamine is an amino sugar used to treat cartilage damage and reduce the pain and progression of arthritis.

Uronic acids have a carboxyl group (-COOH) on the carbon that is not part of the ring. Their names retain the root of the monosaccharides, but the -ose sugar suffix is changed to -uronic acid. For example, galacturonic acid has the same configuration as galactose, and the structure of glucuronic acid corresponds to glucose.

Glucitol or Sorbitol (a sugar alcohol)

Glucosamine (an amino

sugar)

Glucuronic acid(a uronic acid)

< Prev | 1 | 2 | 3 | Next > Carbohydrates - Chemical Structure

Disaccharides consist of two simple sugars

Disaccharide descriptions and components

Disaccharide Description Component monosaccharides

sucrose common table sugar glucose 1α→2 fructose

maltose product of starch hydrolysis glucose 1α→4 glucose

trehalose found in fungi glucose 1α→1 glucose

lactose main sugar in milk galactose 1β→4 glucose

melibiose found in legumes galactose 1α→6 glucose

Sucrose Lactose Maltose

Sucrose, also called saccharose, is ordinary table sugar refined from sugar cane or sugar beets. It is the main ingredient in turbinado sugar, evaporated or dried cane juice, brown sugar, and confectioner's sugar. Lactose has a molecular structure consisting of galactose and glucose. It is of interest because it is associated with lactose intolerance which is the intestinal distress caused

by a deficiency of lactase, an intestinal enzyme needed to absorb and digest lactose in milk. Undigested lactose ferments in the colon and causes abdominal pain, bloating, gas, and diarrhea. Yogurt does not cause these problems because lactose is consumed by the bacteria that transform milk into yogurt.

Maltose consists of two α-D-glucose molecules with the alpha bond at carbon 1 of one molecule attached to the oxygen at carbon 4 of the second molecule. This is called a 1α→4 glycosidic linkage. Trehalose has two α-D-glucose molecules connected through carbon number one in a 1α→1 linkage. Cellobiose is a disaccharide consisting of two β-D-glucose molecules that have a 1β→4 linkage as in cellulose. Cellobiose has no taste, whereas maltose and trehalose are about one-third as sweet as sucrose.

Trisaccharides

Raffinose, also called melitose, is a trisaccharide that is widely found in legumes and cruciferous vegetables, including beans, peas, cabbage, brussels sprouts, and broccoli. It consists of galactose connected to sucrose via a 1α→6 glycosidic linkage. Humans cannot digest saccharides with this linkage and the saccharides are fermented in the large intestine by gas-producing bacteria. Tablets containing the enzyme alpha-galactosidase, such as Beano, are frequently used as digestive aids to prevent gas and bloating. The enzyme is derived from selected strains of the food grade fungus Aspergillus niger.

Raffinose

Polysaccharides are polymers of simple sugars

Many polysaccharides, unlike sugars, are insoluble in water. Dietary fiber includes polysaccharides and oligosaccharides that are resistant to digestion and absorption in the human

small intestine but which are completely or partially fermented by microorganisms in the large intestine. The polysaccharides described below play important roles in nutrition, biology, or food preparation.

Starch

Starch is the major form of stored carbohydrate in plants. Starch is composed of a mixture of two substances: amylose, an essentially linear polysaccharide, and amylopectin, a highly branched polysaccharide. Both forms of starch are polymers of α-D-Glucose. Natural starches contain 10-20% amylose and 80-90% amylopectin. Amylose forms a colloidal dispersion in hot water (which helps to thicken gravies) whereas amylopectin is completely insoluble.

Amylose molecules consist typically of 200 to 20,000 glucose units which form a helix as a result of the bond angles between the glucose units.

Amylose

Amylopectin differs from amylose in being highly branched. Short side chains of about 30

glucose units are attached with 1α→6 linkages approximately every twenty to thirty glucose units along the chain. Amylopectin molecules may contain up to two million glucose units.

Amylopectin

The side branching chains are clustered together within the amylopectin molecule

Starches are transformed into many commercial products by hydrolysis using acids or enzymes as catalysts. Hydrolysis is a chemical reaction in which water is used to break long polysaccharide chains into smaller chains or into simple carbohydrates. The resulting products are assigned a Dextrose Equivalent (DE) value which is related to the degree of hydrolysis. A DE value of 100 corresponds to completely hydrolyzed starch, which is pure glucose (dextrose). Dextrins are a group of low-molecular-weight carbohydrates produced by the hydrolysis of starch. Dextrins are mixtures of polymers of D-glucose units linked by 1α→4 or 1α→6 glycosidic bonds. Maltodextrin is partially hydrolyzed starch that is not sweet and has a DE value less than 20. Syrups, such as corn syrup made from corn starch, have DE values from 20 to 91.  Commercial dextrose has DE values from 92 to 99. Corn syrup solids, which may be labeled as soluble corn fiber or resistant maltodextrin, are mildly sweet semi-crystalline or powdery amorphous products with DEs from 20 to 36 made by drying corn syrup in a vacuum or in spray driers. Resistant maltodextrin or soluble corn fiber are not broken down in the digestive system, but they are partially fermented by colonic bacteria thus providing only 2 Calories per gram instead of the 4 Calories per gram in corn syrup. High Fructose Corn Syrup (HFCS), commonly used to sweeten soft drinks, is made by treating corn syrup with enzymes to convert a portion of the glucose into fructose. Commercial HFCS contains from 42% to 55% fructose, with the remaining percentage being mainly glucose. There is an effort underway to rename High Fructose Corn Syrup as Corn Sugar because of the negative public perception that HFCS contributes to obesity. Modified starch is starch that has been changed by mechanical processes or chemical treatments to stabilize starch gels made with hot water. Without modification, gelled starch-water mixtures lose viscosity or become rubbery after a few hours. Hydrogenated glucose syrup (HGS) is produced by hydrolyzing starch, and then hydrogenating the resulting syrup to produce sugar alcohols like maltitol and sorbitol, along with hydrogenated oligo- and polysaccharides. Polydextrose (poly-D-glucose) is a synthetic, highly-branched polymer with many types of glycosidic linkages created by heating dextrose with an acid catalyst and purifying the resulting water-soluble polymer. Polydextrose is used as a bulking agent because it is tasteless and is similar to fiber in terms of its resistance to digestion. The name resistant starch is applied to dietary starch that is not degraded in the stomach and small intestine, but is fermented by microflora in the large intestine.

Relative sweetness of various carbohydrates

fructose 173

invert sugar* 120

HFCS (42% fructose) 120

sucrose 100

xylitol 100

tagatose 92

glucose 74

high-DE corn syrup 70

sorbitol 55

mannitol 50

trehalose 45

regular corn syrup 40

galactose 32

maltose 32

lactose 15

* invert sugar is a mixture of glucose and fructose found in fruits.

Glycogen

Glucose is stored as glycogen in animal tissues by the process of glycogenesis. When glucose cannot be stored as glycogen or used immediately for energy, it is converted to fat. Glycogen is a polymer of α-D-Glucose identical to amylopectin, but the branches in glycogen tend to be shorter (about 13 glucose units) and more frequent. The glucose chains are organized globularly like branches of a tree originating from a pair of molecules of glycogenin, a protein with a molecular weight of 38,000 that acts as a primer at the core of the structure. Glycogen is easily converted back to glucose to provide energy.

Glycogen

Dextran

Dextran is a polysaccharide similar to amylopectin, but the main chains are formed by 1α→6 glycosidic linkages and the side branches are attached by 1α→3 or 1α→4 linkages. Dextran is an oral bacterial product that adheres to the teeth, creating a film called plaque. It is also used commercially in confections, in lacquers, as food additives, and as plasma volume expanders.

Dextran

Inulin

Some plants store carbohydrates in the form of inulin as an alternative, or in addition, to starch. Inulins are present in many vegetables and fruits, including onions, leeks, garlic, bananas, asparagus, chicory, and Jerusalem artichokes. Inulins, also called fructans, are polymers consisting of fructose units that typically have a terminal glucose. Oligofructose has the same structure as inulin, but the chains consist of 10 or fewer fructose units. Oligofructose has approximately 30 to 50 percent of the sweetness of table sugar. Inulin is less soluble than oligofructose and has a smooth creamy texture that provides a fat-like mouthfeel. Inulin and oligofructose are nondigestible by human intestinal enzymes, but they are totally fermented by colonic microflora. The short-chain fatty acids and lactate produced by fermentation contribute 1.5 kcal per gram of inulin or oligofructose. Inulin and oligofructose are used to replace fat or sugar and reduce the calories of foods like ice cream, dairy products, confections and baked goods.

Inulin n = approx. 35

Carbohydrates - Chemical Structure

Cellulose

Cellulose is a polymer of β-D-Glucose, which in contrast to starch, is oriented with -CH2OH groups alternating above and below the plane of the cellulose molecule thus producing long, unbranched chains. The absence of side chains allows cellulose molecules to lie close together and form rigid structures. Cellulose is the major structural material of plants. Wood is largely cellulose, and cotton is almost pure cellulose. Cellulose can be hydrolyzed to its constituent glucose units by microorganisms that inhabit the digestive tract of termites and ruminants. Cellulose may be modified in the laboratory by treating it with nitric acid (HNO3) to replace all the hydroxyl groups with nitrate groups (-ONO2) to produce cellulose nitrate (nitrocellulose or

guncotton) which is an explosive component of smokeless powder. Partially nitrated cellulose, known as pyroxylin, is used in the manufacture of collodion, plastics, lacquers, and nail polish.

Cellulose

Hemicellulose

The term "hemicellulose" is applied to the polysaccharide components of plant cell walls other than cellulose, or to polysaccharides in plant cell walls which are extractable by dilute alkaline solutions. Hemicelluloses comprise almost one-third of the carbohydrates in woody plant tissue. The chemical structure of hemicelluloses consists of long chains of a variety of pentoses, hexoses, and their corresponding uronic acids. Hemicelluloses may be found in fruit, plant stems, and grain hulls. Although hemicelluloses are not digestible, they can be fermented by yeasts and bacteria. The polysaccharides yielding pentoses on hydrolysis are called pentosans. Xylan is an example of a pentosan consisting of D-xylose units with 1β→4 linkages.

Xylan

Arabinoxylan

Arabinoxylans are polysaccharides found in the bran of grasses and grains such as wheat, rye, and barley. Arabinoxylans consist of a xylan backbone with L-arabinofuranose (L-arabinose in its 5-atom ring form) attached randomly by 1α→2 and/or 1α→3 linkages to the xylose units throughout the chain. Since xylose and arabinose are both pentoses, arabinoxylans are usually classified as pentosans. Arabinoxylans are important in the baking industry. The arabinose units bind water and produce viscous compounds that affect the consistency of dough, the retention of gas bubbles from fermentation in gluten-starch films, and the final texture of baked products.

Arabinoxylan

Chitin

Chitin is an unbranched polymer of N-Acetyl-D-glucosamine. It is found in fungi and is the principal component of arthropod and lower animal exoskeletons, e.g., insect, crab, and shrimp shells. It may be regarded as a derivative of cellulose, in which the hydroxyl groups of the second carbon of each glucose unit have been replaced with acetamido (-NH(C=O)CH3) groups.

Chitin

Beta-Glucan

Beta-glucans consist of linear unbranched polysaccharides of β-D-Glucose like cellulose, but with one 1β→3 linkage for every three or four 1β→4 linkages. Beta-glucans form long cylindrical molecules containing up to about 250,000 glucose units. Beta-glucans occur in the bran of grains such as barley and oats, and they are recognized as being beneficial for reducing heart disease by lowering cholesterol and reducing the glycemic response. They are used comercially to modify food texture and as fat substitutes.

Beta-Glucan

Glycosaminoglycans

Glycosaminoglycans are found in the lubricating fluid of the joints and as components of cartilage, synovial fluid, vitreous humor, bone, and heart valves. Glycosaminoglycans are long unbranched polysaccharides containing repeating disaccharide units that contain either of two amino sugar compounds -- N-acetylgalactosamine or N-acetylglucosamine, and a uronic acid such as glucuronate (glucose where carbon six forms a carboxyl group). Glycosaminoglycans are negatively charged, highly viscous molecules sometimes called mucopolysaccharides. The physiologically most important glycosaminoglycans are hyaluronic acid, dermatan sulfate, chondroitin sulfate, heparin, heparan sulfate, and keratan sulfate. Chondroitin sulfate is composed of β-D-glucuronate linked to the third carbon of N-acetylgalactosamine-4-sulfate as illustrated here. Heparin is a complex mixture of linear polysaccharides that have anticoagulant properties and vary in the degree of sulfation of the saccharide units.

  

  

Chondroitin Sulfate Heparin

Agar and Carrageenan

Agar (agar agar) is extracted from seaweed and is used in many foods as a gelling agent. Agar is a polymer of agarobiose, a disaccharide composed of D-galactose and 3,6-anhydro-L-galactose. Highly refined agar is used as a medium for culturing bacteria, cellular tissues, and for DNA fingerprinting. Agar is used as an ingredient in desserts in Japan and other Asian countries. The gels produced with agar have a crispier texture than the desserts made with animal gelatin.

Carrageenan is a generic term for several polysaccharides also extracted from seaweed. Carrageenan compounds differ from agar in that they have sulfate groups (-OSO3

- ) in place of some hydroxyl groups. Carrageenan is also used for thickening, suspending, and gelling food products.

Agarobiose is the repeating disaccharide unit in agar.

 

Alginic acid, Alginates

Alginate is extracted from seaweeds, such as giant kelp (Macrocystis pyrifera). The chemical constituents of alginate are random sequences of chains of β-D-mannuronic and α-L-guluronic acids attached with 1→4 linkages. Alginates are insoluble in water, but absorb water readily. They are useful as gelling and thickening agents. Alginates are used in the manufacture of textiles, paper, and cosmetics. The sodium salt of alginic acid, sodium alginate, is used in the food industry to increase viscosity and as an emulsifier. Alginates are found in food products such as ice cream and in slimming aids where they serve as appetite suppresants. In dentistry, alginates are used to make dental impressions.

Alginic acid

Galactomannan

Galactomannans are polysaccharides consisting of a mannose backbone with galactose side groups. The mannopyranose units are linked with 1β→4 linkages to which galactopyranose units are attached with 1α→6 linkages. Galactomannans are present in several vegetable gums that are used to increase the viscosity of food products. These are the approximate ratios of mannose to galactose for the following gums:

Fenugreek gum, mannose:galactose 1:1 Guar gum, mannose:galactose 2:1 Tara gum, mannose:galactose 3:1 Locust bean gum or Carob gum, mannose:galactose 4:1

Guar is a legume that has been traditionally cultivated as livestock feed. Guar gum is also known by the name cyamopsis tetragonoloba which is the Latin taxonomy for the guar bean or cluster bean. Guar gum is the ground endosperm of the seeds. Approximately 85% of guar gum is guaran, a water soluble polysaccharide consisting of linear chains of mannose with 1β→4 linkages to which galactose units are attached with 1α→6 linkages. The ratio of mannose to galactose is 2:1. Guar gum has five to eight times the thickening power of starch and has many uses in the pharmaceutical industry, as a food stabilizer, and as a source of dietary fiber.

Guaran is the principal polysaccharide in guar gum. 

 

Pectin

Pectin is a polysaccharide that acts as a cementing material in the cell walls of all plant tissues. The white portion of the rind of lemons and oranges contains approximately 30% pectin. Pectin is the methylated ester of polygalacturonic acid, which consists of chains of 300 to 1000 galacturonic acid units joined with 1α→4 linkages. The Degree of Esterification (DE) affects the gelling properties of pectin. The structure shown here has three methyl ester forms (-COOCH3) for every two carboxyl groups (-COOH), hence it is has a 60% degree of esterification, normally called a DE-60 pectin. Pectin is an important ingredient of fruit preserves, jellies, and jams.

Pectin is a polymer of α-Galacturonic acid with a variable number of methyl ester groups. 

Xanthan Gum

Xanthan gum is a polysaccharide with a β-D-glucose backbone like cellulose, but every second glucose unit is attached to a trisaccharide consisting of mannose, glucuronic acid, and mannose. The mannose closest to the backbone has an acetic acid ester on carbon 6, and the mannose at the

end of the trisaccharide is linked through carbons 6 and 4 to the second carbon of pyruvic acid. Xanthan Gum is produced by the bacterium Xanthomonas campestris, which is found on cruciferous vegetables such as cabbage and cauliflower. The negatively charged carboxyl groups on the side chains cause the molecules to form very viscous fluids when mixed with water. Xanthan gum is used as a thickener for sauces, to prevent ice crystal formation in ice cream, and as a low-calorie substitute for fat. Xanthan gum is frequently mixed with guar gum because the viscosity of the combination is greater than when either one is used alone.

The repeating unit of Xanthan Gum

 

Glucomannan

Glucomannan is a dietary fiber obtained from tubers of Amorphophallus konjac cultivated in Asia. Flour from the konjac tubers is used to make Japanese shirataki noodles, also called konnyaku noodles, which are very low in calories. Glucomannan is used as a hunger suppressant because it produces a feeling of fullness by creating very viscous solutions that retard absorption of the nutrients in food. One gram of this soluble polysaccharide can absorb up to 200 ml of water, so it is also used for absorbent articles such as disposable diapers and sanitary napkins. The polysaccharide consists of glucose (G) and mannose (M) in a proportion of 5:8 joined by 1β→4 linkages. The basic polymeric repeating unit has the pattern: GGMMGMMMMMGGM. Short side chains of 11-16 monosaccharides occur at intervals of 50-60 units of the main chain attached by 1β→3 linkages. Also, acetate groups on carbon 6 occur at every 9-19 units of the main chain. Hydrolysis of the acetate groups favors the formation of intermolecular hydrogen bonds that are responsible for the gelling action.

A portion (GGMM) of the glucomannan repeating unit.The second glucose has an acetate group.

GlucozaInformatii despre monozaharidul glucoza. Structura chimica, proprietati fizice si chimice, izomeri, rol biologic, obtinere.Autor: www.biochimie.lx.ro

Glucoza

Glucoza este compusul organic, apartinând clasei monozaharidelor, care are formula chimica C6H12O6. Glucoza are o singura grupare alcool primar, comparativ cu fructoza care are doua grupari alcool primar. Este o aldohexoza (contine o grupare aldehid). Este principalul zaharid din sange si principala sursa de energie a organismelor. Este larg raspandita in majoritatea tesuturilor vegetale si animale. Glucoza constituie unitatea structurala a polizaharidelor precum amidonul, celuloza si glicogenul. A fost izolata in 1747 de catre Andreas Marggraf. Numele de glucoza a fost dat de Jean Dumas in 1838 si provine din grecescul glycos=dulce, zahar. Structura glucozei a fost descoperita la inceputul secolului de Emil Fischer.

Proprietati

Denumire chimica

6-(hidroximetil)oxan-2,3,4,5-tetrol

Sinonim dextroza

Abrevieri Glc

Formula C6H12O6

Masa moleculara

180,16 g/mol

Punct topire

α -D-glucoza 156oCβ -D-glucoza 150oC

Numar CAS

50-99-7 (D-glucoza)921-60-8 (L-glucoza)

Structura

Glucoza contine sase atomi de carbon (figura 1) si o grupa carbonil (specifica aldehidelor) si este numita uneori aldohexoza. In natura, glucoza exista sub forma de structura aciclica (in unele plante) sau sub forma ciclica. Teoretic, structura ciclica a glucozei apare in urma interactiunii dintre gruparea carbonil si gruparile hidroxil de la carbonii 4 si 5.

Aceste interactiuni sunt reactii de aditie a grupelor hidroxil amintite la grupa carbonil. In solutie apoasa, cele doua forme se afla in echilibru, si la pH 7, forma ciclica este predominanta. La formarea structurii ciclice a glucozei, apare la fosta grupa carbonil o noua grupare hidroxil, care se numeste hidroxil glicozidic si care are o reactivitate mai mare decat celelalte grupe hidroxil din molecula. In acest caz, numerotarea carbonilor incepe de la primul carbon de dupa oxigenul din ciclu, in sens orar.

Inapoi la inceputul paginii

Proprietati fiziceGlucoza este o substanta solida, cristalizata, incolora si solubila in apa. Are un gust dulce. Punctul sau de topire este foarte ridicat, deoarece intre numeroasele sale grupari hidroxil (-OH) se formeaza multe legaturi de hidrogen. Cand sunt incalzite, toate monozaharidele (nu numai glucoza) se descompun inainte de a se topi, in carbon si apa, reactie numita carbonizare. Glucoza are 75% din puterea de indulcire a fructozei (care este luata ca unitate de referinta).

Proprietati chimice1. Reactii comune aldehidelor si cetonelorIn acest tip de reactie are loc aditia unei molecule de H (hidrogen)diatomica la o molecul? de glucoza, aditia avand loc la dubla legatura dintre oxigen si carbon. Leg?tura pi dintre cei doi atomi se rupe, iar cate un atom de hidrogen se leaga la fiecare dintre ei si astfel se produce hexitolul (sorbitol):

glucoza

+ H2

hexitol

2. Reactii caracteristice aldehidelorReactia de oxidare a glucozei cu formare de acid gluconic.

glucoza

+ O2

acid gluconic

Inapoi la inceputul paginii

3. Reactia de esterificareGlucoza, in reactie cu clorura acidului acetic, produce esterul pentacilat al glucozei si acid clorhidric:

4. Reactia de eterificareReactia de eterificare are loc doar cu un ester anorganic, precum sulfatul acid de metil:

Reactia de fermentatieAceasta reactie are loc in prezenta anumitor enzime, care au rol de biocatalizator. Astfel, din glucoza rezulta alcool etilic si apa:

C6H6O12 2C2H5OH + 2CO2 Inapoi la inceputul paginii

Sursa imaginilor (cu exceptia celor marcate cu sigla biochimie.lx.ro): http://ro.wikipedia.org/

FosfolipideleFosfolipide, definitie, structuri, caracterul amfipatic. Structurile pentru fosfatidil colina, fosfatidil

etanolamina, fosfatidil inositol, fosfatidil serina si cardiolipina (difosfatidil glicerol). Autor: Wikipedia

PhospholipidFrom Wikipedia, the free encyclopedia

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Phospholipid

Polar group of the molecule, highlighted in red.The U indicates the uncharged hydrophobic portion of the molecule, highlighted in blue.

Phosphatidyl choline is the major component of lecithin. It is also a source for choline in the synthesis of acetylcholine in cholinergic neurons.

Cell membranes consist of phospholipid bilayers

Phospholipids are a class of lipids and are a major component of all cell membranes as they can form lipid bilayers. Most phospholipids contain a diglyceride, a phosphate group, and a simple organic molecule such as choline; one exception to this rule is sphingomyelin, which is derived from sphingosine instead of glycerol. The first phospholipid identified as such in biological tissues was lecithin, or phosphatidylcholine, in the egg yolk, by Theodore Nicolas Gobley, a French chemist and pharmacist, in 1847.

Contents[hide]

1 Amphipathic character 2 Types of phospholipid

o 2.1 Diacylglyceride structures o 2.2 Phosphosphingolipids

3 Simulations 4 Characterisation 5 Phospholipid synthesis 6 In signal transduction 7 Food technology 8 Phospholipid derivatives 9 Abbreviations used and chemical information of glycerophospholipids 10 See also 11 References

[edit] Amphipathic character

The 'head' of a phospholipid is hydrophilic (attracted to water), while the hydrophobic 'tails' repel water. The hydrophillic head contains the negatively charged phosphate group, and may contain other polar groups. The hydrophobic tail usually consists of long fatty acid hydrocarbon chains. When placed in water, phospholipids form a variety of structures depending on the specific properties of the phospholipid. These specific properties allow phospholipids to play an important role in the phospholipid bilayer. In biological systems, the phospholipids often occur with other molecules (e.g., proteins, glycolipids, cholesterol) in a bilayer such as a cell membrane.[1] Lipid bilayers occur when hydrophobic tails line up against one another, forming a membrane with hydrophilic heads on both sides facing the water.

Such movement can be described by the Fluid Mosaic Model, that describes the membrane as a mosaic of lipid molecules that act as a solvent for all the substances and proteins within it, so proteins and lipid molecules are then free to diffuse laterally through the lipid matrix and migrate over the membrane. Cholesterol contributes to membrane fluidity by hindering the packing together of phospholipids. However, this model has now been superseded, as through the study of lipid polymorphism it is now known that the behaviour of lipids under physiological (and other) conditions is not simple.

[edit] Types of phospholipid

[edit] Diacylglyceride structures

See: Glycerophospholipid

Phosphatidic acid (phosphatidate) (PA)

Phosphatidylethanolamine (cephalin) (PE) Phosphatidylcholine (lecithin) (PC) Phosphatidylserine (PS) Phosphoinositides:

o Phosphatidylinositol (PI)o Phosphatidylinositol phosphate (PIP)o Phosphatidylinositol bisphosphate (PIP2) ando Phosphatidylinositol triphosphate (PIP3).

[edit] Phosphosphingolipids

Ceramide phosphorylcholine (Sphingomyelin) (SPH) Ceramide phosphorylethanolamine (Sphingomyelin) (Cer-PE) Ceramide phosphorylglycerol

[edit] Simulations

Computational simulations of phospholipids are often performed using molecular dynamics with force fields such as GROMOS, CHARMM, or AMBER.

[edit] Characterisation

Phospholipids are optically highly birefringent, i.e. their refractive index is different along their axis as opposed to perpendicular to it. Measurement of birefringence can be achieved using cross polarisers in a microscope to obtain an image of e.g. vesicle walls or using techniques such as dual polarisation interferometry to quantify lipid order or disruption in supported bilayers.

[edit] Phospholipid synthesis

Phospholipid synthesis occurs in the cytosol adjacent to ER membrane that is studded with proteins that act in synthesis (GPAT and LPAAT acyl transferases, phosphatase and choline phosphotransferase) and allocation (flippase and floppase). Eventually a vesicle will bud off from the ER containing phospholipids destined for the cytoplasmic cellular membrane on its exterior leaflet and phospholipids destined for the exoplasmic cellular membrane on its inner leaflet.[2]

[edit] In signal transduction

Some types of phospholipid can be split to produce products that function as second messengers in signal transduction. Examples include phosphatidylinositol (4,5)-bisphosphate (PIP2), that can be split by the enzyme Phospholipase C into inositol triphosphate (IP3) and diacylglycerol (DAG), which both carry out the functions of the Gq type of G protein in response to various stimuli and intervene in various processes from long term depression in neurons[3] to leukocyte signal pathways started by chemokine receptors.[4]

Phospholipids also intervene in prostaglandin signal pathways as the raw material used by lipase enzymes to produce the prostaglandin precursors. In plants they serve as the raw material to produce Jasmonic acid, a plant hormone similar in structure to prostaglandins that mediates defensive responses against pathogens.

[edit] Food technology

Phospholipids can also act as an emulsifier, enabling oils to dissolve in water. Phospholipids called lecithin are extracted out of cooking oil and then used as food additives in many things such as bread and can also be purchased separately in a health food store.

[edit] Phospholipid derivativesSee table below for an extensive list.

Natural phospholipid derivates:

egg PC, egg PG, soy PC, hydrogenated soy PC, sphingomyelin as natural phospholipids.

Synthetic phospholipid derivates: o Phosphatidic acid (DMPA, DPPA, DSPA)o Phosphatidylcholine (DDPC, DLPC, DMPC, DPPC, DSPC, DOPC, POPC, DEPC)o Phosphatidylglycerol (DMPG, DPPG, DSPG, POPG)o Phosphatidylethanolamine (DMPE, DPPE, DSPE DOPE)o Phosphatidylserine (DOPS)o PEG phospholipid (mPEG-phospholipid, polyglycerin-phospholipid, funcitionalized-

phospholipid, terminal activated-phospholipid)

[edit] Abbreviations used and chemical information of glycerophospholipidsAbbreviation CAS Name Type

DDPC3436-44-0

1,2-Didecanoyl-sn-glycero-3-phosphocholine

Phosphatidylcholine

DEPA-NA80724-31-8

1,2-Dierucoyl-sn-glycero-3-phosphate (Sodium Salt)

Phosphatidic acid

DEPC56649-39-9

1,2-Dierucoyl-sn-glycero-3-phosphocholine Phosphatidylcholine

DEPE 988-07-21,2-Dierucoyl-sn-glycero-3-phosphoethanolamine

Phosphatidylethanolamine

DEPG-NA1,2-Dierucoyl-sn-glycero-3[Phospho-rac-(1-glycerol...) (Sodium Salt)

Phosphatidylglycerol

DLOPC 998-06-11,2-Dilinoleoyl-sn-glycero-3-phosphocholine

Phosphatidylcholine

DLPA-NA1,2-Dilauroyl-sn-glycero-3-phosphate (Sodium Salt)

Phosphatidic acid

DLPC18194-25-7

1,2-Dilauroyl-sn-glycero-3-phosphocholine Phosphatidylcholine

DLPE1,2-Dilauroyl-sn-glycero-3-phosphoethanolamine

Phosphatidylethanolamine

DLPG-NA1,2-Dilauroyl-sn-glycero-3[Phospho-rac-(1-glycerol...) (Sodium Salt)

Phosphatidylglycerol

DLPG-NH41,2-Dilauroyl-sn-glycero-3[Phospho-rac-(1-glycerol...) (Ammonium Salt)

Phosphatidylglycerol

DLPS-NA1,2-Dilauroyl-sn-glycero-3-phosphoserine (Sodium Salt)

Phosphatidylserine

DMPA-NA 80724-31,2-Dimyristoyl-sn-glycero-3-phosphate (Sodium Salt)

Phosphatidic acid

DMPC18194-24-6

1,2-Dimyristoyl-sn-glycero-3-phosphocholine

Phosphatidylcholine

DMPE 988-07-21,2-Dimyristoyl-sn-glycero-3-phosphoethanolamine

Phosphatidylethanolamine

DMPG-NA67232-80-8

1,2-Dimyristoyl-sn-glycero-3[Phospho-rac-(1-glycerol...) (Sodium Salt)

Phosphatidylglycerol

DMPG-NH41,2-Dimyristoyl-sn-glycero-3[Phospho-rac-(1-glycerol...) (Ammonium Salt)

Phosphatidylglycerol

DMPG-NH4/NA1,2-Dimyristoyl-sn-glycero-3[Phospho-rac-(1-glycerol...) (Sodium/Ammonium Salt)

Phosphatidylglycerol

DMPS-NA1,2-Dimyristoyl-sn-glycero-3-phosphoserine (Sodium Salt)

Phosphatidylserine

DOPA-NA1,2-Dioleoyl-sn-glycero-3-phosphate (Sodium Salt)

Phosphatidic acid

DOPC4235-95-4

1,2-Dioleoyl-sn-glycero-3-phosphocholine Phosphatidylcholine

DOPE 4004-5-1-1,2-Dioleoyl-sn-glycero-3-phosphoethanolamine

Phosphatidylethanolamine

DOPG-NA62700-69-0

1,2-Dioleoyl-sn-glycero-3[Phospho-rac-(1-glycerol...) (Sodium Salt)

Phosphatidylglycerol

DOPS-NA70614-14-1

1,2-Dioleoyl-sn-glycero-3-phosphoserine (Sodium Salt)

Phosphatidylserine

DPPA-NA71065-87-7

1,2-Dipalmitoyl-sn-glycero-3-phosphate (Sodium Salt)

Phosphatidic acid

DPPC 63-89-81,2-Dipalmitoyl-sn-glycero-3-phosphocholine

Phosphatidylcholine

DPPE 923-61-51,2-Dipalmitoyl-sn-glycero-3-phosphoethanolamine

Phosphatidylethanolamine

DPPG-NA67232-81-9

1,2-Dipalmitoyl-sn-glycero-3[Phospho-rac-(1-glycerol...) (Sodium Salt)

Phosphatidylglycerol

DPPG-NH473548-70-6

1,2-Dipalmitoyl-sn-glycero-3[Phospho-rac-(1-glycerol...) (Ammonium Salt)

Phosphatidylglycerol

DPPS-NA1,2-Dipalmitoyl-sn-glycero-3-phosphoserine (Sodium Salt)

Phosphatidylserine

DSPA-NA108321-18-2

1,2-Distearoyl-sn-glycero-3-phosphate (Sodium Salt)

Phosphatidic acid

DSPC 816-94-4 1,2-Distearoyl-sn-glycero-3-phosphocholine Phosphatidylcholine

DSPE1069-79-0

1,2-Distearoyl-sn-glycero-3-phosphoethanolamine

Phosphatidylethanolamine

DSPG-NA67232-82-0

1,2-Distearoyl-sn-glycero-3[Phospho-rac-(1-glycerol...) (Sodium Salt)

Phosphatidylglycerol

DSPG-NH4108347-80-4

1,2-Distearoyl-sn-glycero-3[Phospho-rac-(1-glycerol...) (Ammonium Salt)

Phosphatidylglycerol

DSPS-NA 1,2-Distearoyl-sn-glycero-3-phosphoserine Phosphatidylserine

(Sodium Salt)

Egg Sphingomyelin empty Liposome

EPC Egg-PC Phosphatidylcholine

HEPC Hydrogenated Egg PC Phosphatidylcholine

HSPC High purity Hydrogenated Soy PC Phosphatidylcholine

HSPC Hydrogenated Soy PC Phosphatidylcholine

LYSOPC MYRISTIC18194-24-6

1-Myristoyl-sn-glycero-3-phosphocholine Lysophosphatidylcholine

LYSOPC PALMITIC17364-16-8

1-Palmitoyl-sn-glycero-3-phosphocholine Lysophosphatidylcholine

LYSOPC STEARIC19420-57-6

1-Stearoyl-sn-glycero-3-phosphocholine Lysophosphatidylcholine

Milk Sphingomyelin MPPC

1-Myristoyl-2-palmitoyl-sn-glycero 3-phosphocholine

Phosphatidylcholine

MSPC1-Myristoyl-2-stearoyl-sn-glycero-3–phosphocholine

Phosphatidylcholine

PMPC1-Palmitoyl-2-myristoyl-sn-glycero-3–phosphocholine

Phosphatidylcholine

POPC26853-31-6

1-Palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine

Phosphatidylcholine

POPE1-Palmitoyl-2-oleoyl-sn-glycero-3-phosphoethanolamine

Phosphatidylethanolamine

POPG-NA81490-05-3

1-Palmitoyl-2-oleoyl-sn-glycero-3[Phospho-rac-(1-glycerol)...] (Sodium Salt)

Phosphatidylglycerol

PSPC1-Palmitoyl-2-stearoyl-sn-glycero-3–phosphocholine

Phosphatidylcholine

SMPC1-Stearoyl-2-myristoyl-sn-glycero-3–phosphocholine

Phosphatidylcholine

SOPC1-Stearoyl-2-oleoyl-sn-glycero-3-phosphocholine

Phosphatidylcholine

SPPC1-Stearoyl-2-palmitoyl-sn-glycero-3-phosphocholine

Phosphatidylcholine

See also

Galactolipid Sulfolipid

GlycerophospholipidFrom Wikipedia, the free encyclopedia

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Glycerol

Phosphoglyceride

Glycerophospholipids or phosphoglycerides are glycerol-based phospholipids. They are the main component of biological membranes.

Contents[hide]

1 Structures 2 Nomenclature and stereochemistry 3 Examples of glycerophospholipids 4 Uses

o 4.1 Use in membranes o 4.2 Use in emulsification

5 External links 6 See also 7 External links

[edit] Structures

The term glycerophospholipid signifies any derivative of sn-glycero-3-phosphoric acid that contains at least one O-acyl, or O-alkyl, or O-alk-1'-enyl residue attached to the glycerol moiety and a polar head made of a nitrogenous base, a glycerol or an inositol unit.

It contains a glycerol core with fatty acids. They can be the same or different subunits of fatty acids.

Carbon 1 (tail, apolar) contains a fatty acid, typically saturated Carbon 2 (tail, apolar) contains a fatty acid, typically unsaturated and in the cis conformation,

thus appearing "bent" Carbon 3 (head, polar) contains a phosphate group or an alcohol attached to a phosphate group

[edit] Nomenclature and stereochemistry

In general, glycerophospholipids use a "sn" notation, which stands for stereochemical numbering. When the letters "sn" appear in the nomenclature, by convention the hydroxyl group of the second carbon of glycerol (sn-2) is on the left on a Fischer projection. The numbering follows the one of Fischer's projections, being sn-1 the carbon at the top and sn-3 the one at the bottom.

The advantage of this particular notation is that the spatial conformation (R or L) of the glycero-molecule is determined intuitively by the residues on the positions sn-1 and sn-3.

For example sn-glycero-3-phosphoric acid and sn-glycero-1-phosphoric acid are enantiomers.

[edit] Examples of glycerophospholipidsName Image Head Image Charge

Phosphatidyl choline (lecithin)

choline neutral

Phosphatidyl ethanolamine (cephalin)

ethanolamine neutral

Phosphatidyl inositol inositol negative

Phosphatidyl serine serine negative

Bisphosphatidyl glycerol (cardiolipin)

- - negative

Lecithin and cephalin are more common than the others in most human membranes, but cardiolipin is quite common in the inner membranes of mitochondria.

[edit] Uses

[edit] Use in membranes

One of a glycerophospholipid's functions is to serve as a structural component of cell membranes. The cell membrane seen under the electron microscope consists of two identifiable layers, or "leaflets", each of which is made up of an ordered row of glycerophospholipid molecules. The composition of each layer can vary widely depending on the type of cell.

For example, in human erythrocytes the cytosolic side (the side facing the cytosol) of the plasma membrane consists mainly of phosphatidylethanolamine, phosphatidylserine, and phosphatidylinositol.

By contrast, the exoplasmic side (the side on the exterior of the cell) consists mainly of phosphatidylcholine and sphingomyelin, a type of sphingolipid.

Each glycerophospholipid molecule consists of a small polar head group and two long hydrophobic chains. In the cell membrane, the two layers of phospholipids are arranged as follows:

the hydrophobic tails point to each other and form a fatty, hydrophobic center the ionic head groups are placed at the inner and outer surfaces of the cell membrane

This is a stable structure because the ionic hydrophilic head groups interact with the aqueous media inside and outside the cell, whereas the hydrophobic tails maximize hydrophobic interactions with each other and are kept away from the aqueous environments. The overall result of this structure is to construct a fatty barrier between the cell's interior and its surroundings.

[edit] Use in emulsification

Glycerophospholipids can also act as an emulsifying agent to promote dispersal of one substance into another. This is sometimes used in candy making and ice-cream making.

[edit] External links

Diagram at uca.edu

[edit] See also

Phospholipid Biological membrane

Phosphatidic acidFrom Wikipedia, the free encyclopedia

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Phosphatidic acids (PAs) are the acid forms of phosphatidates, a part of common phospholipids, major constituents of cell membranes. Phosphatidic acids are the simplest diacyl-glycerophospholipids.[1]

Contents[hide]

1 Structure 2 Formation and degradation 3 The role of PA in the cell 4 PA as a biosynthetic precursor 5 Biophysical properties of PA 6 Measurement of PA production 7 PA as a signalling lipid 8 Proteins known to interact with PA 9 References 10 External links

[edit] Structure

General chemical structure of phosphatidic acids

Phosphatidic acid consists of a glycerol backbone, with, in general, a saturated fatty acid bonded to carbon-1, an saturated fatty acid bonded to carbon-2, and a phosphate group bonded to carbon-3.[1][2]

[edit] Formation and degradation

Besides de novo synthesis, PA can be formed in three ways:

By phospholipase D (PLD), via the hydrolysis of the P-O bond of phosphatidylcholine (PC) to produce PA and choline.[3]

By the phosphorylation of diacylglycerol (DAG) by DAG kinase (DAGK) By the acylation of lysophosphatidic acid by lysoPA-acyltransferase (LPAAT); this is the most

common pathway [4].

PA is degraded by conversion into DAG by lipid phosphate phosphohydrolases (LPPs)[5][6] or into lyso-PA by phospholipase A (PLA).

[edit] The role of PA in the cell

The role of PA in the cell can be divided into three categories:

PA is the precursor for the biosynthesis of many other lipids. The physical properties of PA influence membrane curvature. PA acts as a signaling lipid, recruiting cytosolic proteins to appropriate membranes (e.g.,

sphingosine kinase 1 [7] ).

These three roles are not mutually exclusive. For example, PA may be involved in vesicle formation by promoting membrane curvature and by recruiting the proteins to carry out the much more energetically unfavourable task of neck formation and pinching.

[edit] PA as a biosynthetic precursor

PA is a vital cell lipid that acts as a biosynthetic precursor for the formation (directly or indirectly) of all acylglycerol lipids in the cell.[8]

In mammalian and yeast cells, two different pathways are known for the de novo synthesis of PA, the glycerol 3-phosphate pathway or the dihydroxyacetone phosphate pathway. In bacteria, only the former pathway is present, and mutations that block this pathway are lethal, demonstrating the importance of PA. In mammalian and yeast cells, where the enzymes in these pathways are redundant, mutation of any one enzyme is not lethal. However, it is worth noting that in vitro, the various acyltransferases exhibit different substrate specificities with respect to the acyl-CoAs that are incorporated into PA. Different acyltransferases also have different intracellular distributions, such as the endoplasmic reticulum (ER), the mitochondria or

peroxisomes, and local concentrations of activated fatty acids. This suggests that the various acyltransferases present in mammalian and yeast cells may be responsible for producing different pools of PA.[8]

The conversion of PA into diacylglycerol (DAG) by LPPs is the commitment step for the production of phosphatidylcholine (PC), phosphatidylethanolamine (PE) and phosphatidylserine (PS). In addition, DAG is also converted into CDP-DAG, which is a precursor for phosphatidylglycerol (PG), phosphatidylinositol (PI) and phosphoinositides (PIP, PIP2, PIP3).[8]

PA concentrations are maintained at extremely low levels in the cell by the activity of potent LPPs.[5] These convert PA into DAG very rapidly and, because DAG is the precursor for so many other lipids, it too is soon metabolised into other membrane lipids. This means that any upregulation in PA production can be matched, over time, with a corresponding upregulation in LPPs and in DAG metabolising enzymes.

PA is, therefore, essential for lipid synthesis and cell survival, yet, under normal conditions, is maintained at very low levels in the cell.

[edit] Biophysical properties of PA

PA is a unique phospholipid in that it has a small highly-charged head group that is very close to the glycerol backbone. PA is known to play roles in both vesicle fission[9] and fusion[10], and these roles may relate to the biophysical properties of PA.

At sites of membrane budding or fusion, the membrane becomes or is highly curved. A major event in the budding of vesicles, such as transport carriers from the Golgi, is the creation and subsequent narrowing of the membrane neck. Studies have suggested that this process may be lipid-driven, and have postulated a central role for DAG due to its, likewise, unique molecular shape. The presence of two acyl chains but no headgroup results in a large negative curvature in membranes.[11]

The LPAAT BARS-50 has also been implicated in budding from the Golgi.[9] This suggests that the conversion of lysoPA into PA might affect membrane curvature. LPAAT activity doubles the number of acyl chains, greatly increasing the cross-sectional area of the lipid that lies ‘within’ the membrane while the surface headgroup remains unchanged. This can result in a more negative membrane curvature. Researchers from Utrecht University have looked at the effect of lysoPA versus PA on membrane curvature by measuring the effect these have on the transition temperature of PE from lipid bilayers to nonlamellar phases using 31P-NMR.[12] The curvature induced by these lipids was shown to be dependent not only on the structure of lsyoPA versus PA but also on dynamic properties, such as the hydration of head groups and inter- and intramolecular interactions. For instance, Ca2+ may interact with two PAs to form a neutral but highly-curved complex. The neutralisation of the otherwise repulsive charges of the headgroups and the absence of any steric hindrance enables strong intermolecular interactions between the acyl chains, resulting in PA-rich microdomains. Thus in vitro, physiological changes in pH, temperature, and cation concentrations have strong effects on the membrane curvature induced by PA and lysoPA.[12] The interconversion of lysoPA, PA, and DAG - and changes in pH and

cation concentration - can cause membrane bending and destabilisation, playing a direct role in membrane fission simply by virtue of their biophysical properties. However, though PA and lysoPA have been shown to affect membrane curvature in vitro; their role in vivo is unclear.

The roles of lysoPA, PA, and DAG in promoting membrane curvature do not preclude a role in recruiting proteins to the membrane. For instance, the Ca2+ requirement for the fusion of complex liposomes is not greatly affected by the addition of annexin I, though it is reduced by PLD. However, with annexin I and PLD, the extent of fusion is greatly enhanced, and the Ca2+ requirement is reduced almost 1000-fold to near physiological levels.[10]

Thus the metabolic, biophysical, recruitment, and signaling roles of PA may be interrelated.

[edit] Measurement of PA production

As PA is rapidly converted to DAG, it is very short-lived in the cell. This means that it is difficult to measure PA production and therefore to study the role of PA in the cell. However, PLD activity can be measured by the addition of primary alcohols to the cell. [13] PLD then carries out a transphosphatidylation reaction, instead of hydrolysis, producing phosphatidyl alcohols in place of PA. The phosphatidyl alcohols are metabolic dead-ends, and can be readily extracted and measured. Thus PLD activity and PA production (if not PA itself) can be measured, and, by blocking the formation of PA, the involvement of PA in cellular processes can be inferred.

[edit] PA as a signalling lipid

As described above, PLD hydrolyses PC to form PA and choline. Because choline is very abundant in the cell, PLD activity does not significantly affect choline levels; and choline is unlikely to play any role in signaling.

The role of PLD activation in numerous signaling contexts, combined with the lack of a role for choline, suggests that PA is important in signaling. However, PA is rapidly converted to DAG, and DAG is also known to be a signaling molecule. This raises the question as to whether PA has any direct role in signaling or whether it simply acts as a precursor for DAG production.[14][15] If it is found that PA acts only as a DAG precursor, then one can raise the question as to why cells should produce DAG using two enzymes when they contain the PLC that could produce DAG in a single step.

PA produced by PLD or by DAGK can be distinguished by the addition of [γ-32P]ATP. This will show whether the phosphate group is newly derived from the kinase activity or whether it originates from the PC.[16]

Although PA and DAG are interconvertible, they do not act in the same pathways. Stimuli that activate PLD do not activate enzymes downstream of DAG, and vice versa. For example it was shown that addition of PLD to membranes results in the production of [32P]-labeled PA and [32P]-labeled phosphoinositides.[17] The addition of DAGK inhibitors eliminates the production of [32P]-labeled PA but not the PLD-stimulated production of phosphoinositides.

It is possible that, though PA and DAG are interconvertible, separate pools of signaling and non-signaling lipids may be maintained. Studies have suggested that DAG signaling is mediated by polyunsaturated DAG, whereas PLD-derived PA is monounsaturated or saturated. Thus functional saturated/monounsaturated PA can be degraded by hydrolysing it to form non-functional saturated/monounsaturated DAG, whereas functional polyunsaturated DAG can be degraded by converting it into non-functional polyunsaturated PA.[14][18]

This model suggests that PA and DAG effectors should be able to distinguish lipids with the same headgroups but with differing acyl chains. Although some lipid-binding proteins are able to insert themselves into membranes and could hypothetically recognise the type of acyl chain or the resulting properties of the membrane, many lipid-binding proteins are cytosolic and localise to the membrane by binding only the headgroups of lipids. Perhaps the different acyl chains can affect the angle of the head-group in the membrane. If this is the case, it suggests that a PA-binding domain must not only be able to bind PA specifically but must also be able to identify those head-groups that are at the correct angle. Whatever the mechanism is, such specificity is possible. It is seen in the pig testes DAGK that is specific for polyunsaturated DAG[19] and in two rat hepatocyte LPPs that dephosphorylate different PA species with different activities.[20] Moreover, the stimulation of SK1 activity by PS in vitro was shown to vary greatly depending on whether dioleoyl (C18:1), distearoyl (C18:0), or 1-stearoyl, 2-oleoyl species of PS were used.[21] Thus it seems that, though PA and DAG are interconvertible, the different species of lipid can have different biological activities; and this may enable the two lipids to maintain separate signaling pathways.

[edit] Proteins known to interact with PA

SK1 PDE4A1 Raf1 mTOR PP1 SHP1 Spo20p p47phox PKCε PLC β PIP5K .

PhosphatidylethanolamineFrom Wikipedia, the free encyclopedia

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Phosphatidylethanolamine

Other names[hide]

cephalin

Identifiers

PubChem 446872

ChemSpider 394115

MeSH phosphatidylethanolamines

SMILES

[show]InChI

[show]

(what is this?) (verify)Except where noted otherwise, data are given for materials

in their standard state (at 25 °C, 100 kPa)

Infobox references

Phosphatidylethanolamine (cephalin, sometimes abbreviated PE) is a lipid found in biological membranes. It is synthesized by the addition of CDP-ethanolamine to diglyceride, releasing CMP. S-adenosyl methionine can subsequently methylate the amine of phosphatidyl ethanolamine to yield phosphatidyl choline.

Cephalin is a phospholipid, which is a lipid derivative. It is not to be confused with the molecule of the same name that is an alkaloid constituent of Ipecac.

Contents[hide]

1 Function 2 Chemistry 3 External links 4 See also 5 Additional images 6 References

[edit] Function

Cephalin is found in all living cells, although in human physiology it is found particularly in nervous tissue such as the white matter of brain, nerves, neural tissue, and in spinal cord. Whereas lecithin is the principal phospholipid in animals, cephalin is the principal one in bacteria.

As a polar head group, phosphatidylethanolamine (PE) creates a more viscous lipid membrane compared to phosphatidylcholine (PC). For example, the melting temperature of di-oleoyl-PE is -16C while the melting temperature of di-oleoyl-PC is -20C. If the lipids had two palmitoyl chains, PE would melt at 63C while PC would melt already at 41C (See references in Wan et al. Biochemistry 47 2008). Lower melting temperatures correspond, in a simplistic view, to more fluid membranes.

[edit] Chemistry

In the chemical sense, cephalin is phosphatidylethanolamine. Like lecithin, it consists of a combination of glycerol esterified with two fatty acids and phosphoric acid. Whereas the phosphate group is combined with choline in Lecithin, it is combined with the ethanolamine in Cephalin.

The two fatty acids may be the same, or different, and are usually in the 1,2 positions (though can be in the 1,3 positions).

[edit] External links

MeSH Cephalins

[edit] See also

Phosphatidyl ethanolamine methyltransferase

[edit] Additional images

membrane lipids

ethanolamine

PhosphatidylcholineFrom Wikipedia, the free encyclopedia

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Phosphatidylcholines are a class of phospholipids that incorporate choline as a headgroup. They are a major component of biological membranes and can be easily obtained from a variety of readily available sources such as egg yolk or soy beans from which they are mechanically extracted or chemically extracted using hexane. They are also a member of the lecithin group of yellow-brownish fatty substances occurring in animal and plant tissues.

The name "lecithin" was originally defined from the Greek lekithos (λεκιθος, egg yolk) by Theodore Nicolas Gobley, a French chemist and pharmacist of the mid-19th century, who applied it to the egg yolk phosphatidylcholine that he identified in 1847 and finally completely described from a chemical structural point of view in 1874.

Phosphatidylcholine (sometimes abbreviated as PC) is more common on the exoplasmic or outer leaflet of a cell membrane.

Fig 1. 1 example of variant phosphatidylcholine, palmitoyl-oleyl-sn-phosphatidylcholine. .

In general, a phosphatidylcholine is obtained combining a choline head group and glycerophosphoric acid with a variety of fatty acids, one being a saturated fatty acid (in the example, here palmitic or hexadecanoic acid, H3C-(CH2)14-COOH; margaric acid identified by Gobley in egg yolk, or heptadecanoic acid H3C-(CH2)15-COOH, also belong to that class); and one being an unsaturated fatty acid (here oleic acid, or 9Z-octadecenoic acid, as in Gobley's original egg yolk lecithin).

Phosphatidylcholines are such a major component of lecithin that in some contexts the terms are sometimes used as synonyms. However, lecithin extract consists of a mixture of phosphatidylcholine and other compounds. It is also used along with sodium taurocholate for simulating fed- and fasted-state biorelevant media in dissolution studies of highly-lipophilic drugs. Phosphatidylcholine is a major constituent of cell membranes, and also plays a role in membrane-mediated cell signalling.

Phospholipase D catalyzes the hydrolysis of phosphatidylcholine to form phosphatidic acid (PA), releasing the soluble choline headgroup into the cytosol.

Some organizations are promoting injected phosphatidylcholine, otherwise known as injection lipolysis, claiming the procedure can break down fat cells, and thus serve as an alternative to liposuction. It is important to note that while the procedure cites early experiments that showed lipolysis in cases of fat emboli,[1] no peer-reviewed studies have shown any amount of lipolysis even remotely comparable to liposuction.[2][3]

The molecular weight is 760.09 g/mol.[4]

Contents[hide]

1 Health 2 See also 3 Additional images 4 References 5 External links

[edit] HealthThis section does not cite any references or sources.Please help improve this article by adding citations to reliable sources. Unsourced material may be challenged and removed. (August 2010)

Phosphatidylcholine is a vital substance that is in every cell in the human body. At birth and throughout infancy, phosphatidylcholine concentrations are high (as high as 90% of the cell membrane), but it is slowly depleted throughout the course of life, and may drop to as low as 10% of the cellular membrane in the elderly[citation needed]. As is such, some researchers in the fields of health and nutrition have begun to recommend daily supplementation of phosphatidylcholine as a way of slowing down senescence [5] and improving brain functioning and memory capacity.[6]

Recent studies point to the many potential benefits of phosphatidylcholine for liver repair. One study shows phosphatidylcholine's healing effect with hepatitis A, hepatitis B, and hepatitis C. Phosphatidylcholine administration for chronic, active hepatitis resulted in significant reduction of disease activity.[7]

[edit] See also

CDP choline Lysophosphatidylcholine Theodore Nicolas Gobley , discoverer of egg yolk lecithin, the first in history phosphatidylcholine Saturated fatty acid Unsaturated fatty acid

[edit] Additional images

Membrane lipidsCholine metabolismPhosphatidate

Choline

Membrane lipidsFrom Wikipedia, the free encyclopedia

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The major membrane lipidsPtdCho - Phosphatidylcholine; PtdEtn - Phosphatidylethanolamine; PtdIns - Phosphatidylinositol; PtdSer - Phosphatidylserine.

The three major classes of membrane lipids are phospholipids, glycolipids, and cholesterol.

Phosphatidate

Contents[hide]

1 Phospholipids 2 Glycolipids 3 Fatty acids 4 Phosphoglycerides 5 Sphingosine 6 Cholesterol 7 See also 8 References 9 External links

[edit] Phospholipids

Phospholipids and glycolipids consist of two long, nonpolar (hydrophobic) hydrocarbon chains linked to a hydrophilic head group.

The heads of phospholipids are phosphorylated and they consist of either:

Glycerol (and hence the name phosphoglycerides given to this group of lipids). Sphingosine (with only one member - sphingomyelin).

[edit] Glycolipids

The heads of glycolipids contain a sphingosine with one or several sugar units attached to it. The hydrophobic chains belong either to:

two fatty acids - in the case of the phosphoglycerides. one FA and the hydrocarbon tail of sphingosine - in the case of sphingomyelin and the

glycolipids.

[edit] Fatty acids

The fatty acids in phospho- and glycolipids usually contain an even number of carbon atoms, typically between 14 and 24. The 16- and 18-carbon FAs are the most common ones. FAs may be saturated or unsaturated, with the configuration of the double bonds nearly always cis. The length and the degree of unsaturation of FAs chains have a profound effect on membranes' fluidity.

[edit] Phosphoglycerides

In phosphoglycerides, the hydroxyl groups at C-1 and C-2 of glycerol are esterified to the carboxyl groups of the FAs. The C-3 hydroxyl group is esterified to phosphoric acid. The

resulting compound, called phosphatidate, is the simplest phosphoglycerate. Only small amounts of phosphatidate are present in membranes. However, it is a key intermediate in the biosynthesis of the other phosphoglycerides.

[edit] Sphingosine

Sphingosine is an amino alcohol that contains a long, unsaturated hydrocarbon chain. In sphingomyelin and glycolipids, the amino group of sphingosine is linked to FAs by an amide bond. In sphingomyelin the primary hydroxyl group of sphingosine is esterified to phosphoryl choline. In glycolipids, the sugar component is attached to this group. The simplest glycolipid is cerebroside, in which there is only one sugar residue, either Glc or Gal. More complex glycolipids, such as gangliosides, contain a branched chain of as many as seven sugar residues.

[edit] Cholesterol

Space-filling models of sphingomyelin (a) and cholesterol (b).

Cholesterol occurs naturally in eukaryote cell membranes where it is bio-synthesised from mevalonate via a squalene cyclisation of terpenoids. It associated preferentially with sphingolipids (see diagram) in cholesterol-rich lipid rafts areas of the membranes in eukaryotic cells.[1] Hopanoids serve a similar function in prokaryotes.

Cell membranes require high levels - typically an average of 20% cholesterol molecular in the whole membrane, increasing locally in raft areas up to 50% cholesterol (- % is molecular ratio) [2]

Formation of lipid rafts promotes aggregation of peripheral and transmembrane proteins including docking of SNARE and VAMP proteins[3]

[edit] See also

Lipid bilayer Homeoviscous adaptation

choline

PhosphatidylserineFrom Wikipedia, the free encyclopedia

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Phosphatidylserine

Identifiers

CAS number 8002-43-5

PubChem 445141

ChemSpider 13628254

SMILES

[show]InChI

[show]

Properties

Molecular formula C13H24NO10P

Molar mass 385.304

(what is this?) (verify)Except where noted otherwise, data are given for materials

in their standard state (at 25 °C, 100 kPa)

Infobox references

Phosphatidylserine (abbreviated Ptd-L-Ser or PS) is a phospholipid component, usually kept on the inner-leaflet (the cytosolic side) of cell membranes by an enzyme called flippase. When a cell undergoes apoptotic cell death phosphatidylserine is no longer restricted to the cytosolic part of the membrane, but becomes exposed on the surface of the cell.[citation needed]

Contents[hide]

1 Possible Health benefits o 1.1 Memory and cognition o 1.2 Sports nutrition o 1.3 Attention-deficit hyperactivity disorder

2 Safety 3 Dietary sources 4 Applications

o 4.1 Research o 4.2 Tumors

5 References 6 External links

[edit] Possible Health benefits

[edit] Memory and cognition

Early studies of phosphatidylserine distilled the chemical from bovine brain. Because of concerns about Bovine Spongiform Encephalopathy, however, modern studies and commercially available products are made from soybeans. The fatty acids attached to the serine in the soy product are not identical to those in the bovine product, which is also impure. Preliminary studies in rats indicate that the soy product is at least as effective as that of bovine origin. [1][2] However,

later clinical trials in humans found that "a daily supplement of S-PS (soybean derived PS) does not affect memory or other cognitive functions in older individuals with memory complaints."[3]

On May 13, 2003, the U.S. Food and Drug Administration stated "based on its evaluation of the totality of the publicly available scientific evidence, the agency concludes that there is not significant scientific agreement among qualified experts that a relationship exists between phosphatidylserine and reduced risk of dementia or cognitive dysfunction." FDA also stated "of the 10 intervention studies that formed the basis of FDA's evaluation, all were seriously flawed or limited in their reliability in one or more ways." It concludes that "most of the evidence does not support a relationship between phosphatidylserine and reduced risk of dementia or cognitive dysfunction, and that the evidence that does support such a relationship is very limited and preliminary." FDA did, however give "qualified health claim" status to phosphatidylserine, stating that "Consumption of phosphatidylserine may reduce the risk of dementia in the elderly" and "Consumption of phosphatidylserine may reduce the risk of cognitive dysfunction in the elderly".

[edit] Sports nutrition

Phosphatidylserine has been demonstrated to speed up recovery, prevent muscle soreness, improve well-being, and might possess ergogenic properties in athletes involved in cycling, weight training and endurance running. Soy-PS, in a dose dependent manner (400 mg), has been reported to be an effective supplement for combating exercise-induced stress by blunting the exercise-induced increase in cortisol levels.[4] PS supplementation promotes a desirable hormonal balance for athletes and might attenuate the physiological deterioration that accompanies overtraining and/or overstretching.[5] In recent studies, PS has been shown to enhance mood in a cohort of young people during mental stress and to improve accuracy during tee-off by increasing the stress resistance of golfers.[6]

[edit] Attention-deficit hyperactivity disorder

First pilot studies indicate that PS supplementation might be beneficial for children with attention-deficit hyperactivity disorder.[7][8]

[edit] Safety

Traditionally, PS supplements were derived from bovine cortex (BC-PS); however, due to the potential transfer of infectious diseases, soy-derived PS (S-PS) has been established as a potential safe alternative. Soy-derived PS is Generally Recognized As Safe (GRAS) and is a safe nutritional supplement for older persons if taken up to a dosage of 200 mg three times daily. [9] Phosphatidylserine has been shown to reduce specific immune response in mice. [10][11]

[edit] Dietary sources

PS can be found in meat, but is most abundant in the brain and in innards such as liver and kidney. Only small amounts of PS can be found in dairy products or in vegetables, with the exception of white beans.

Table 1. PS content in different foods.[12]

FoodPS Content in mg/100

g

Bovine brain 713

Atlantic mackerel 480

Chicken heart 414

Atlantic herring 360

Eel 335

Offal (average value) 305

Pig's spleen 239

Pig's kidney 218

Tuna 194

Chicken leg, with skin, without bone

134

Chicken liver 123

White beans 107

Soft-shell clam 87

Chicken breast, with skin 85

Mullet 76

Veal 72

Beef 69

Pork 57

Pig's liver 50

Turkey leg, without skin or bone 50

Turkey breast without skin 45

Crayfish 40

Cuttlefish 31

Atlantic cod 28

Anchovy 25

Whole grain barley 20

European hake 17

European pilchard (sardine) 16

Trout 14

Soy lecithin 10-20[citation needed]

Rice (unpolished) 3

Carrot 2

Ewe's Milk 2

Cow's Milk (whole, 3.5% fat) 1

Potato 1

The average daily PS intake from the diet in Western countries is estimated to be 130 mg.

[edit] Applications

[edit] Research

Annexin-A5 is a naturally-occurring protein with avid binding affinity for PS. Labeled-annexin-A5 enables visualization of cells in the early- to mid-apoptotic state in vitro or in vivo. Another PS binding protein is Mfge8.

[edit] Tumors

Technetium-labeled annexin-A5 enables distinction between malignant and benign tumours whose pathology includes a high rate of cell division and apoptosis in malignant compared with a low rate of apoptosis in benign tumors.

PhosphatidylinositolFrom Wikipedia, the free encyclopedia

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Phosphatidylinositol

Other names[hide]

PI, PtdIns

Properties

Molecular formula

C47H83O13P

Molar mass 886.56 g/mol, neutral with fatty acid

composition - 18:0, 20:4

Except where noted otherwise, data are given for materials in their standard state (at 25 °C, 100 kPa)

Infobox references

Phosphatidylinositol (abbreviated PtdIns, or PI) is a negatively charged phospholipid and a minor component in the cytosolic side of eukaryotic cell membranes.

The inositol can be phosphorylated to form phosphatidylinositol phosphate (PIP), phosphatidylinositol bisphosphate (PIP2) and phosphatidylinositol trisphosphate (PIP3). PIP, PIP2

and PIP3 are collectively called phosphoinositides.

Contents[hide]

1 Biosynthesis 2 Chemistry 3 Phosphoinositides 4 References 5 See also 6 Additional images 7 External links

[edit] Biosynthesis

Biosynthesis of phosphatidylinositol catalyzed by phosphatidylinositol synthase. Figure adapted from Christopher, K.; van Holde, K.E.; Ahern, Kevin G. Biochemistry Third Edition. Pearson Education, Inc: Singapore, 2005; p 678.[1].

The synthesis of phosphatidylinositol is catalyzed by phosphatidylinositol synthase and involves CDP-diacylglycerol and L-myo-inositol.[1].

[edit] Chemistry

PI has a polar and non-polar region, making the lipid an amphiphile. Amphiphatic lipids demonstrate polymorphic behavior, a current academic research topic. Phosphatidylinositol is classified as a glycerophospholipid that contains a glycerol backbone, two non-polar fatty acid tails, a phosphate group substituted with an inositol polar head group.

The most common fatty acids of phosphoinositides are stearic acid in the SN1 position and arachidonic acid, in the SN2 position. Hydrolysis of phosphoinositides yield one mole of glycerol, two moles of fatty acids, one mole of inositol and one, two, or three moles of phosphoric acids, depending on the number of phosphates on the inositol rings. Phosphoinositides are regarded as the most acidic phospholipid.

[edit] Phosphoinositides

Phosphorylated forms of phosphatidylinositol are called phosphoinositides and play important roles in lipid signaling, cell signaling and membrane trafficking. The inositol ring can be phosphorylated by a variety of kinases on the three, four and five hydroxyl groups in seven different combinations. However, the two and six hydroxyl group is typically not phosphorylated due to steric hindrance.

All seven variations of the following phosphoinositides have been found in animals:

Phosphatidylinositol monophosphates:

Phosphatidylinositol 3-phosphate , also known as PtdIns3P or PI(3)P Phosphatidylinositol 4-phosphate , also known as PtdIns4P or PI(4)P Phosphatidylinositol 5-phosphate , also known as PtdIns5P or PI(5)P

Phosphatidylinositol bisphophosphates:

Phosphatidylinositol 3,4-bisphosphate , also known as PtdIns(3,4)P or PI(3,4)P2

Phosphatidylinositol 3,5-bisphosphate , also known as PtdIns(3,5)P or PI(3,5)P2

Phosphatidylinositol 4,5-bisphosphate , also known as PtdIns(4,5)P or PI(4,5)P2

Phosphatidylinositol trisphophosphate:

Phosphatidylinositol 3,4,5-trisphosphate , also known as PtdIns(3,4,5)P or PI(3,4,5)P3

These phosphoinositides are also found in plant cells, with the exception of PIP3[2].

[edit] References

1. ^ a b Mathews, Chrisotphe K.; van Holde, K.E.; Ahern, Kevin G., (2005). Biochemistry Third Edition.

2. ̂ Muller-Roeber B, Pical C; , (2002). Inositol Phospholipid Metabolism in Arabidopsis. Characterized and Putative Isoforms of Inositol Phospholipid Kinase and Phosphoinositide-Specific Phospholipase C.

[edit] See also

Wikimedia Commons has media related to: Phosphatidylinositol

PI 3-kinase Inositol phosphate Phosphatidylinositol 3-phosphate Phosphatidylinositol 4-phosphate Phosphatidylinositol 5-phosphate Phosphatidylinositol (3,4)-bisphosphate Phosphatidylinositol (3,5)-bisphosphate Phosphatidylinositol (4,5)-bisphosphate Inositol 1,4,5-triphosphate Phosphatidylinositol (3,4,5)-trisphosphate inositol pentakisphosphate inositol hexaphosphate inositol triphosphate receptor

[edit] Additional images

Membrane lipids

Phosphatidyl-inositol

Inositol Glycerol

Phosphatidylinositol phosphateFrom Wikipedia, the free encyclopedia

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Phosphatidylinositol phosphate may refer to:

Phosphatidylinositol 3-phosphate , also known as PI(3)P Phosphatidylinositol 4-phosphate , also known as PI(4)P Phosphatidylinositol 5-phosphate , also known as PI(5)P

Phosphatidylinositol 3-phosphateFrom Wikipedia, the free encyclopedia

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Phosphatidylinositol 3-phosphate

Other names[hide]

sn-1-stearoyl-2-arachidonoyl phosphatidylinositol 3-phosphate

Identifiers

PubChem 6857403

Properties

Molecular formula

C11H20O16P2

Molar mass470.214 g/mol, neutral with fatty acid composition - 18:0, 20:4

Except where noted otherwise, data are given for materials in their standard state (at 25 °C, 100 kPa)

Infobox references

Phosphatidylinositol 3-phosphate (PtdIns3P or PI3P) is a phospholipid found in cell membranes that helps to recruit a range of proteins, many of which are involved in protein trafficking, to the membranes. It is the product of both the class II and III phosphoinositide 3-kinases (PI 3-kinases) activity on phosphatidylinositol.

PtdIns3P is dephophosphorylated by the myotubularin family of phosphatases, on the D3 position of the inositol ring, and can be converted to PtdIns(3,5) P 2 by the lipid kinase PIKfyve.

Both FYVE domains and PX domains – found in proteins such as SNX1, Hrs, and EEA1 – bind to PtdIns3P.

The majority of PtdIns3P appears to be constitutively synthesised by the class III PI 3-kinase, Vps34, at endocytic membranes. Class II PI 3-kinases also appear to synthesise PtdIns3P, their activity however appears to be regulated by a range of stimuli, including growth factors. This suggests that specific pools of PtdIns3P may be synthesised upon cell stimulation.

Phosphatidylinositol 4-phosphateFrom Wikipedia, the free encyclopedia

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Phosphatidylinositol 4-phosphate (PtdIns4P or PI4P) is a precursor of Phosphatidylinositol (4,5)-bisphosphate. PtdIns4P is prevalent in the membrane of the Golgi apparatus.

In the Golgi apparatus, PtdIns4P binds to the GTP-binding protein ARF and to effector proteins, including four-phosphate-adaptor protein 1 and 2 (FAPP1 and FAPP2).[1] This three molecule complex recruits proteins that need to be carried to the cell membrane.[2]

Phosphatidylinositol 5-phosphateFrom Wikipedia, the free encyclopedia

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Phosphatidylinositol 5-phosphate (PtdIns5P or PI5P) is one of the seven phosphoinositides, and is the last to have been discovered to be naturally occurring.

In 1997 Lucia Rameh, while working as a postdoctoral fellow with Lewis C. Cantley observed that the enzymes referred to as type II PIP-kinases did not utilize PtdIns4P as a substrate (as had been proposed). In fact, they required PtdIns5P as a substrate to produce PtdIns(4,5)P2. The observation immediately suggested that cells must contain a natural pool of PtdIns(5)P, a prediction that was verified by Rameh, Cantley, and colleagues.[1]

The function of PtdIns5P remains uncertain, especially since no specific PtdIns5P-binding proteins have been unambiguously identified. There is some thought that it may function in membrane trafficking from late endosomes to the plasma membrane.[2]

Phosphatidylinositol bisphosphateFrom Wikipedia, the free encyclopedia

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Phosphatidylinositol bisphosphate may refer to:

Phosphatidylinositol (3,4)-bisphosphate Phosphatidylinositol (3,5)-bisphosphate Phosphatidylinositol (4,5)-bisphosphate

Phosphatidylinositol 3,4-bisphosphateFrom Wikipedia, the free encyclopedia

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General structure

Chemical structure of sn-1-stearoyl-2-arachidonoyl phosphatidylinositol (3,4)-bisphosphate

Phosphatidylinositol (3,4)-bisphosphate (PtdIns(3,4)P2) is a minor phospholipid component of cell membranes, yet an important second messenger. The generation of PtdIns(3,4)P2 at the plasma membrane activates a number of important cell signaling pathways.

PtdIns(3,4)P2 is dephophosphorylated by the phosphatase INPP4B on the 4 position of the inositol ring and by the TPTE (transmembrane phosphatases with tensin homology) family of phosphatases on the 4 position of the inositol ring.

The PH domain in a number of proteins binds to PtdIns(3,4)P2 including the PH domain in PKB. The generation of PtdIns(3,4)P2 at the plasma membrane upon the activation of class I PI 3-kinases and SHIP phosphatases causes these proteins to translocate to the plasma membrane, thereby effecting their activity.

Phosphatidylinositol 3,5-bisphosphateFrom Wikipedia, the free encyclopedia

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Chemical structure of sn-1-stearoyl-2-arachidonoyl phosphatidylinositol (3,5)-bisphosphate

Phosphatidylinositol (3,5)-bisphosphate (PtdIns(3,5)P2 or PI(3,5)P2) is a minor phospholipid component of cell membranes, yet important in distinguishing cell compartments. The generation of PtdIns(3,5)P2 in intracellular membranes by the lipid kinase PIKfyve recruits a number of important proteins involved in regulating intracellular trafficking[1].

PtdIns(3,5)P2 is dephophosphorylated at the 5 position by the phosphatase FIG4, and by members of the myotubularin lipid phosphatase family at the 3 position of the inositol ring generating Phosphatidylinositol 5-phosphate (PtdIns5P).

The phosphoinositide-binding domain in a number of proteins binds to PtdIns(3,5)P2, including the PH domain in centaurin-β2[citation needed], the PX domain of SNX1[citation needed], and a WD40 repeat domain in Atg18p[2].

Phosphatidylinositol 4,5-bisphosphateFrom Wikipedia, the free encyclopedia

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"PIP2" redirects here. For other uses, see PIP2 (disambiguation).

Phosphatidylinositol 4,5-bisphosphate

IUPAC name [hide]

1,2-Diacyl-sn-glycero-3-phospho-(1-D-myo-inositol 4,5-bisphosphate)

Identifiers

CAS number 245126-95-8

PubChem 5497157

Properties

Molecular formula C47H80O19P3

Molar mass 1042.05 g/mol

(what is this?) (verify)Except where noted otherwise, data are given for materials

in their standard state (at 25 °C, 100 kPa)

Infobox references

Phosphatidylinositol 4,5-bisphosphate or PtdIns(4,5)P2, also known simply as PIP2, is a minor phospholipid component of cell membranes. PtdIns(4,5)P2 is enriched at the plasma membrane where it is a substrate for a number of important signaling proteins.[1]

PtdIns(4,5)P22 is formed primarily by the type I phosphatidylinositol 4 phosphate 5 kinases from PI(4)P.

The fatty acids of PIP2 are variable in different species and tissues, but studies show the most common fatty acids are stearic in position 1 and arachidonic in 2.[2]

Contents[hide]

1 Functions o 1.1 IP3/DAG pathway o 1.2 Docking phospholipids

2 Additional images 3 References

[edit] Functions

[edit] IP3/DAG pathway

Main article: IP3/DAG pathway

PtdIns(4,5)P2 functions as an intermediate in the IP3/DAG pathway, which is initiated by ligands binding to G protein-coupled receptors activating the Gq alpha subunit. PtdIns(4,5)P2 is a substrate for hydrolysis by phospholipase C (PLC), a membrane-bound enzyme activated through protein receptors like α1 adrenergic receptors. The products of this reaction are inositol 1,4,5-triphosphate (InsP3; IP3) and diacylglycerol (DAG), both of which function as second messengers. In this cascade, DAG remains on the cell membrane and activates the signal cascade by activating protein kinase C (PKC). PKC in turn activates other cytosolic proteins by phosphorylating them. The effect of PKC could be reversed by phosphatases. IP3 enters the cytoplasm and activates IP3 receptors on the smooth endoplasmic reticulum (ER), which opens calcium channels on the smooth ER, allowing mobilization of calcium ions through specific Ca2+

channels into the cytosol. Calcium participates in the cascade by activating other proteins.

[edit] Docking phospholipids

Further information: phosphatidylinositol (3,4,5)-trisphosphate

Class I PI 3-kinases phosphorylate PtdIns(4,5)P2 forming phosphatidylinositol (3,4,5)-trisphosphate (PtdIns(3,4,5)P3). Both PtdIns(3,4,5)P3 and PtdIns(4,5)P2 not only act as substrates for enzymes but also serve as docking phospholipids that bind specific domains that promote the recruitment of proteins to the plasma membrane and subsequent activation of signaling cascades.

Examples of proteins activated by PtdIns(3,4,5)P3 are AKT, PDPK1, Btk1. One mechanism for direct effect of PtdIns(4,5)P2 is opening of Na + channels as a minor function

in growth hormone release by growth hormone-releasing hormone.[3]

[edit] Additional images

PIP2 cleavage to IP3 and DAG initiates intracellular calcium release and PKC activation.

Phosphatidylinositol (3,4,5)-trisphosphateFrom Wikipedia, the free encyclopedia

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Phosphatidylinositol (3,4,5)-trisphosphate

Other names[hide]

PI(3,4,5)P3, PtdIns(3,4,5)P3

Properties

Molecular formula

C47H86O22P4

Molar mass1126.46 g/mol, neutral with fatty acid composition - 18:0, 20:4

(what is this?) (verify)

Except where noted otherwise, data are given for materials in their standard state (at 25 °C, 100 kPa)

Infobox references

Phosphatidylinositol (3,4,5)-trisphosphate (PtdIns(3,4,5)P3), abbreviated PIP3, is the product of the class I phosphoinositide 3-kinases (PI 3-kinases) phosphorylation on phosphatidylinositol (4,5)-bisphosphate (PIP2).

[edit] Discovery

In the mid-1980s, Lewis C. Cantley published a series of papers describing the discovery of a novel type of phosphoinositide kinase with the unprecedented ability to phosphorylate the 3' position of the inositol ring.[1] Subsequent studies demonstrated that in vivo the enzyme prefers PtdIns(4,5)P2 as a substrate, producing the product PIP3.[2] PIP3 had been previously identified in human neutrophils following stimulation with chemotactic peptide [3]

[edit] Function

PIP3 functions to activate downstream signaling components, the most notable one being the protein kinase AKT, which activates downstream anabolic signaling pathways required for cell growth and survival.

PtdIns(3,4,5)P3 is dephosphorylated by the phosphatase PTEN on the 3 position, generating PI(4,5)P2, and by SHIPs (SH2-containing inositol phosphatase) on the 5' position of the inositol ring, producing PI(3,4)P2.

The PH domain in a number of proteins binds to PtdIns(3,4,5)P3. Such proteins include Akt/PKB, PDK1, Btk1, and ARNO. The generation of PtdIns(3,4,5)P3 at the plasma membrane upon the activation of class I PI 3-kinases causes these proteins to translocate to the plasma membrane and affects their activity accordingly.

The PH domain allows binding between PtdIns(3,4,5)P3 and G protein-coupled receptor kinases (GRKs). This enhances the binding of the GRK to the plasma membrane.

Phosphatidic acidFrom Wikipedia, the free encyclopedia

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Phosphatidic acids (PAs) are the acid forms of phosphatidates, a part of common phospholipids, major constituents of cell membranes. Phosphatidic acids are the simplest diacyl-glycerophospholipids.[1]

Contents[hide]

1 Structure 2 Formation and degradation 3 The role of PA in the cell 4 PA as a biosynthetic precursor 5 Biophysical properties of PA 6 Measurement of PA production 7 PA as a signalling lipid 8 Proteins known to interact with PA 9 References 10 External links

[edit] Structure

General chemical structure of phosphatidic acids

Phosphatidic acid consists of a glycerol backbone, with, in general, a saturated fatty acid bonded to carbon-1, an saturated fatty acid bonded to carbon-2, and a phosphate group bonded to carbon-3.[1][2]

[edit] Formation and degradation

Besides de novo synthesis, PA can be formed in three ways:

By phospholipase D (PLD), via the hydrolysis of the P-O bond of phosphatidylcholine (PC) to produce PA and choline.[3]

By the phosphorylation of diacylglycerol (DAG) by DAG kinase (DAGK) By the acylation of lysophosphatidic acid by lysoPA-acyltransferase (LPAAT); this is the most

common pathway [4].

PA is degraded by conversion into DAG by lipid phosphate phosphohydrolases (LPPs)[5][6] or into lyso-PA by phospholipase A (PLA).

[edit] The role of PA in the cell

The role of PA in the cell can be divided into three categories:

PA is the precursor for the biosynthesis of many other lipids. The physical properties of PA influence membrane curvature. PA acts as a signaling lipid, recruiting cytosolic proteins to appropriate membranes (e.g.,

sphingosine kinase 1 [7] ).

These three roles are not mutually exclusive. For example, PA may be involved in vesicle formation by promoting membrane curvature and by recruiting the proteins to carry out the much more energetically unfavourable task of neck formation and pinching.

[edit] PA as a biosynthetic precursor

PA is a vital cell lipid that acts as a biosynthetic precursor for the formation (directly or indirectly) of all acylglycerol lipids in the cell.[8]

In mammalian and yeast cells, two different pathways are known for the de novo synthesis of PA, the glycerol 3-phosphate pathway or the dihydroxyacetone phosphate pathway. In bacteria, only the former pathway is present, and mutations that block this pathway are lethal, demonstrating the importance of PA. In mammalian and yeast cells, where the enzymes in these pathways are redundant, mutation of any one enzyme is not lethal. However, it is worth noting that in vitro, the various acyltransferases exhibit different substrate specificities with respect to the acyl-CoAs that are incorporated into PA. Different acyltransferases also have different intracellular distributions, such as the endoplasmic reticulum (ER), the mitochondria or peroxisomes, and local concentrations of activated fatty acids. This suggests that the various acyltransferases present in mammalian and yeast cells may be responsible for producing different pools of PA.[8]

The conversion of PA into diacylglycerol (DAG) by LPPs is the commitment step for the production of phosphatidylcholine (PC), phosphatidylethanolamine (PE) and phosphatidylserine

(PS). In addition, DAG is also converted into CDP-DAG, which is a precursor for phosphatidylglycerol (PG), phosphatidylinositol (PI) and phosphoinositides (PIP, PIP2, PIP3).[8]

PA concentrations are maintained at extremely low levels in the cell by the activity of potent LPPs.[5] These convert PA into DAG very rapidly and, because DAG is the precursor for so many other lipids, it too is soon metabolised into other membrane lipids. This means that any upregulation in PA production can be matched, over time, with a corresponding upregulation in LPPs and in DAG metabolising enzymes.

PA is, therefore, essential for lipid synthesis and cell survival, yet, under normal conditions, is maintained at very low levels in the cell.

[edit] Biophysical properties of PA

PA is a unique phospholipid in that it has a small highly-charged head group that is very close to the glycerol backbone. PA is known to play roles in both vesicle fission[9] and fusion[10], and these roles may relate to the biophysical properties of PA.

At sites of membrane budding or fusion, the membrane becomes or is highly curved. A major event in the budding of vesicles, such as transport carriers from the Golgi, is the creation and subsequent narrowing of the membrane neck. Studies have suggested that this process may be lipid-driven, and have postulated a central role for DAG due to its, likewise, unique molecular shape. The presence of two acyl chains but no headgroup results in a large negative curvature in membranes.[11]

The LPAAT BARS-50 has also been implicated in budding from the Golgi.[9] This suggests that the conversion of lysoPA into PA might affect membrane curvature. LPAAT activity doubles the number of acyl chains, greatly increasing the cross-sectional area of the lipid that lies ‘within’ the membrane while the surface headgroup remains unchanged. This can result in a more negative membrane curvature. Researchers from Utrecht University have looked at the effect of lysoPA versus PA on membrane curvature by measuring the effect these have on the transition temperature of PE from lipid bilayers to nonlamellar phases using 31P-NMR.[12] The curvature induced by these lipids was shown to be dependent not only on the structure of lsyoPA versus PA but also on dynamic properties, such as the hydration of head groups and inter- and intramolecular interactions. For instance, Ca2+ may interact with two PAs to form a neutral but highly-curved complex. The neutralisation of the otherwise repulsive charges of the headgroups and the absence of any steric hindrance enables strong intermolecular interactions between the acyl chains, resulting in PA-rich microdomains. Thus in vitro, physiological changes in pH, temperature, and cation concentrations have strong effects on the membrane curvature induced by PA and lysoPA.[12] The interconversion of lysoPA, PA, and DAG - and changes in pH and cation concentration - can cause membrane bending and destabilisation, playing a direct role in membrane fission simply by virtue of their biophysical properties. However, though PA and lysoPA have been shown to affect membrane curvature in vitro; their role in vivo is unclear.

The roles of lysoPA, PA, and DAG in promoting membrane curvature do not preclude a role in recruiting proteins to the membrane. For instance, the Ca2+ requirement for the fusion of complex

liposomes is not greatly affected by the addition of annexin I, though it is reduced by PLD. However, with annexin I and PLD, the extent of fusion is greatly enhanced, and the Ca2+ requirement is reduced almost 1000-fold to near physiological levels.[10]

Thus the metabolic, biophysical, recruitment, and signaling roles of PA may be interrelated.

[edit] Measurement of PA production

As PA is rapidly converted to DAG, it is very short-lived in the cell. This means that it is difficult to measure PA production and therefore to study the role of PA in the cell. However, PLD activity can be measured by the addition of primary alcohols to the cell. [13] PLD then carries out a transphosphatidylation reaction, instead of hydrolysis, producing phosphatidyl alcohols in place of PA. The phosphatidyl alcohols are metabolic dead-ends, and can be readily extracted and measured. Thus PLD activity and PA production (if not PA itself) can be measured, and, by blocking the formation of PA, the involvement of PA in cellular processes can be inferred.

[edit] PA as a signalling lipid

As described above, PLD hydrolyses PC to form PA and choline. Because choline is very abundant in the cell, PLD activity does not significantly affect choline levels; and choline is unlikely to play any role in signaling.

The role of PLD activation in numerous signaling contexts, combined with the lack of a role for choline, suggests that PA is important in signaling. However, PA is rapidly converted to DAG, and DAG is also known to be a signaling molecule. This raises the question as to whether PA has any direct role in signaling or whether it simply acts as a precursor for DAG production.[14][15] If it is found that PA acts only as a DAG precursor, then one can raise the question as to why cells should produce DAG using two enzymes when they contain the PLC that could produce DAG in a single step.

PA produced by PLD or by DAGK can be distinguished by the addition of [γ-32P]ATP. This will show whether the phosphate group is newly derived from the kinase activity or whether it originates from the PC.[16]

Although PA and DAG are interconvertible, they do not act in the same pathways. Stimuli that activate PLD do not activate enzymes downstream of DAG, and vice versa. For example it was shown that addition of PLD to membranes results in the production of [32P]-labeled PA and [32P]-labeled phosphoinositides.[17] The addition of DAGK inhibitors eliminates the production of [32P]-labeled PA but not the PLD-stimulated production of phosphoinositides.

It is possible that, though PA and DAG are interconvertible, separate pools of signaling and non-signaling lipids may be maintained. Studies have suggested that DAG signaling is mediated by polyunsaturated DAG, whereas PLD-derived PA is monounsaturated or saturated. Thus functional saturated/monounsaturated PA can be degraded by hydrolysing it to form non-

functional saturated/monounsaturated DAG, whereas functional polyunsaturated DAG can be degraded by converting it into non-functional polyunsaturated PA.[14][18]

This model suggests that PA and DAG effectors should be able to distinguish lipids with the same headgroups but with differing acyl chains. Although some lipid-binding proteins are able to insert themselves into membranes and could hypothetically recognise the type of acyl chain or the resulting properties of the membrane, many lipid-binding proteins are cytosolic and localise to the membrane by binding only the headgroups of lipids. Perhaps the different acyl chains can affect the angle of the head-group in the membrane. If this is the case, it suggests that a PA-binding domain must not only be able to bind PA specifically but must also be able to identify those head-groups that are at the correct angle. Whatever the mechanism is, such specificity is possible. It is seen in the pig testes DAGK that is specific for polyunsaturated DAG[19] and in two rat hepatocyte LPPs that dephosphorylate different PA species with different activities.[20] Moreover, the stimulation of SK1 activity by PS in vitro was shown to vary greatly depending on whether dioleoyl (C18:1), distearoyl (C18:0), or 1-stearoyl, 2-oleoyl species of PS were used.[21] Thus it seems that, though PA and DAG are interconvertible, the different species of lipid can have different biological activities; and this may enable the two lipids to maintain separate signaling pathways.

[edit] Proteins known to interact with PA

SK1 PDE4A1 Raf1 mTOR PP1 SHP1 Spo20p p47phox PKCε PLC β PIP5K .

PhosphatidylcholineFrom Wikipedia, the free encyclopedia

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Phosphatidylcholines are a class of phospholipids that incorporate choline as a headgroup. They are a major component of biological membranes and can be easily obtained from a variety of readily available sources such as egg yolk or soy beans from which they are mechanically extracted or chemically extracted using hexane. They are also a member of the lecithin group of yellow-brownish fatty substances occurring in animal and plant tissues.

The name "lecithin" was originally defined from the Greek lekithos (λεκιθος, egg yolk) by Theodore Nicolas Gobley, a French chemist and pharmacist of the mid-19th century, who applied it to the egg yolk phosphatidylcholine that he identified in 1847 and finally completely described from a chemical structural point of view in 1874.

Phosphatidylcholine (sometimes abbreviated as PC) is more common on the exoplasmic or outer leaflet of a cell membrane.

Fig 1. 1 example of variant phosphatidylcholine, palmitoyl-oleyl-sn-phosphatidylcholine. .

In general, a phosphatidylcholine is obtained combining a choline head group and glycerophosphoric acid with a variety of fatty acids, one being a saturated fatty acid (in the example, here palmitic or hexadecanoic acid, H3C-(CH2)14-COOH; margaric acid identified by Gobley in egg yolk, or heptadecanoic acid H3C-(CH2)15-COOH, also belong to that class); and one being an unsaturated fatty acid (here oleic acid, or 9Z-octadecenoic acid, as in Gobley's original egg yolk lecithin).

Phosphatidylcholines are such a major component of lecithin that in some contexts the terms are sometimes used as synonyms. However, lecithin extract consists of a mixture of phosphatidylcholine and other compounds. It is also used along with sodium taurocholate for simulating fed- and fasted-state biorelevant media in dissolution studies of highly-lipophilic drugs. Phosphatidylcholine is a major constituent of cell membranes, and also plays a role in membrane-mediated cell signalling.

Phospholipase D catalyzes the hydrolysis of phosphatidylcholine to form phosphatidic acid (PA), releasing the soluble choline headgroup into the cytosol.

Some organizations are promoting injected phosphatidylcholine, otherwise known as injection lipolysis, claiming the procedure can break down fat cells, and thus serve as an alternative to liposuction. It is important to note that while the procedure cites early experiments that showed lipolysis in cases of fat emboli,[1] no peer-reviewed studies have shown any amount of lipolysis even remotely comparable to liposuction.[2][3]

The molecular weight is 760.09 g/mol.[4]

Contents[hide]

1 Health 2 See also 3 Additional images 4 References 5 External links

[edit] HealthThis section does not cite any references or sources.Please help improve this article by adding citations to reliable sources. Unsourced material may be challenged and removed. (August 2010)

Phosphatidylcholine is a vital substance that is in every cell in the human body. At birth and throughout infancy, phosphatidylcholine concentrations are high (as high as 90% of the cell membrane), but it is slowly depleted throughout the course of life, and may drop to as low as 10% of the cellular membrane in the elderly[citation needed]. As is such, some researchers in the fields of health and nutrition have begun to recommend daily supplementation of phosphatidylcholine as a way of slowing down senescence [5] and improving brain functioning and memory capacity.[6]

Recent studies point to the many potential benefits of phosphatidylcholine for liver repair. One study shows phosphatidylcholine's healing effect with hepatitis A, hepatitis B, and hepatitis C. Phosphatidylcholine administration for chronic, active hepatitis resulted in significant reduction of disease activity.[7]

[edit] See also

CDP choline Lysophosphatidylcholine Theodore Nicolas Gobley , discoverer of egg yolk lecithin, the first in history phosphatidylcholine Saturated fatty acid Unsaturated fatty acid

[edit] Additional images

Choline metabolismPhosphatidate

Choline

Membrane lipids

PhosphatidylglycerolFrom Wikipedia, the free encyclopedia

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Phosphatidylglycerol is a glycerophospholipid found in pulmonary surfactant.

The general structure of phosphatidylglycerol consists of a L-glycerol 3-phosphate backbone ester-bonded to either saturated or unsaturated fatty acids on carbons 1 and 2. The head group substituent glycerol is bonded through a phosphomonoester. It is the precursor of surfactant and its presence in the amniotic fluid of the newborn indicates fetal lung maturity.

Approximately 98% of alveolar wall surface area is due to the presence of type I cells, with type II cells producing pulmonary surfactant covering around 2% of the alveolar walls. Once surfactant is secreted by the type II cells, it must be spread over the remaining type I cellular surface area. Phosphatidylglycerol is thought to be important in spreading of surfactant over the Type I cellular surface area. The major surfactant deficiency in premature infants relates to the lack of phosphatidylglycerol, even though it comprises less than 5% of pulmonary surfactant phospholipids.

[edit] Biosynthesis

L-glycerol-3-phosphate is activated by a CTP and pyrophosphate is cleaved off resulting in CDP-diglycerol. Glycerol-3-phosphate is attached to CDP-diglycerol and phosphatidylglycerol phosphate is formed, while CMP is released. The phosphate group is hydrolysed forming phosphatidylglycerol. Two phosphatidylglycerols form cardiolipin, the constituent molecule of the mitochondrial inner membrane.

[edit] See also

glycerol cardiolipin

PhosphatidylethanolamineFrom Wikipedia, the free encyclopedia

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Phosphatidylethanolamine

Other names[hide]

cephalin

Identifiers

PubChem 446872

ChemSpider 394115

MeSH phosphatidylethanolamines

SMILES

[show]InChI

[show]

(what is this?) (verify)Except where noted otherwise, data are given for materials

in their standard state (at 25 °C, 100 kPa)

Infobox references

Phosphatidylethanolamine (cephalin, sometimes abbreviated PE) is a lipid found in biological membranes. It is synthesized by the addition of CDP-ethanolamine to diglyceride, releasing CMP. S-adenosyl methionine can subsequently methylate the amine of phosphatidyl ethanolamine to yield phosphatidyl choline.

Cephalin is a phospholipid, which is a lipid derivative. It is not to be confused with the molecule of the same name that is an alkaloid constituent of Ipecac.

Contents[hide]

1 Function 2 Chemistry 3 External links 4 See also 5 Additional images 6 References

[edit] Function

Cephalin is found in all living cells, although in human physiology it is found particularly in nervous tissue such as the white matter of brain, nerves, neural tissue, and in spinal cord. Whereas lecithin is the principal phospholipid in animals, cephalin is the principal one in bacteria.

As a polar head group, phosphatidylethanolamine (PE) creates a more viscous lipid membrane compared to phosphatidylcholine (PC). For example, the melting temperature of di-oleoyl-PE is -16C while the melting temperature of di-oleoyl-PC is -20C. If the lipids had two palmitoyl chains, PE would melt at 63C while PC would melt already at 41C (See references in Wan et al. Biochemistry 47 2008). Lower melting temperatures correspond, in a simplistic view, to more fluid membranes.

[edit] Chemistry

In the chemical sense, cephalin is phosphatidylethanolamine. Like lecithin, it consists of a combination of glycerol esterified with two fatty acids and phosphoric acid. Whereas the phosphate group is combined with choline in Lecithin, it is combined with the ethanolamine in Cephalin.

The two fatty acids may be the same, or different, and are usually in the 1,2 positions (though can be in the 1,3 positions).

PhosphatidylserineFrom Wikipedia, the free encyclopedia

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Phosphatidylserine

Identifiers

CAS number 8002-43-5

PubChem 445141

ChemSpider 13628254

SMILES

[show]InChI

[show]

Properties

Molecular formula C13H24NO10P

Molar mass 385.304

(what is this?) (verify)Except where noted otherwise, data are given for materials

in their standard state (at 25 °C, 100 kPa)

Infobox references

Phosphatidylserine (abbreviated Ptd-L-Ser or PS) is a phospholipid component, usually kept on the inner-leaflet (the cytosolic side) of cell membranes by an enzyme called flippase. When a cell undergoes apoptotic cell death phosphatidylserine is no longer restricted to the cytosolic part of the membrane, but becomes exposed on the surface of the cell.[citation needed]

Contents[hide]

1 Possible Health benefits o 1.1 Memory and cognition o 1.2 Sports nutrition o 1.3 Attention-deficit hyperactivity disorder

2 Safety 3 Dietary sources 4 Applications

o 4.1 Research o 4.2 Tumors

5 References 6 External links

[edit] Possible Health benefits

[edit] Memory and cognition

Early studies of phosphatidylserine distilled the chemical from bovine brain. Because of concerns about Bovine Spongiform Encephalopathy, however, modern studies and commercially available products are made from soybeans. The fatty acids attached to the serine in the soy product are not identical to those in the bovine product, which is also impure. Preliminary studies in rats indicate that the soy product is at least as effective as that of bovine origin. [1][2] However, later clinical trials in humans found that "a daily supplement of S-PS (soybean derived PS) does not affect memory or other cognitive functions in older individuals with memory complaints."[3]

On May 13, 2003, the U.S. Food and Drug Administration stated "based on its evaluation of the totality of the publicly available scientific evidence, the agency concludes that there is not significant scientific agreement among qualified experts that a relationship exists between phosphatidylserine and reduced risk of dementia or cognitive dysfunction." FDA also stated "of the 10 intervention studies that formed the basis of FDA's evaluation, all were seriously flawed or limited in their reliability in one or more ways." It concludes that "most of the evidence does not support a relationship between phosphatidylserine and reduced risk of dementia or cognitive dysfunction, and that the evidence that does support such a relationship is very limited and preliminary." FDA did, however give "qualified health claim" status to phosphatidylserine, stating that "Consumption of phosphatidylserine may reduce the risk of dementia in the elderly" and "Consumption of phosphatidylserine may reduce the risk of cognitive dysfunction in the elderly".

[edit] Sports nutrition

Phosphatidylserine has been demonstrated to speed up recovery, prevent muscle soreness, improve well-being, and might possess ergogenic properties in athletes involved in cycling,

weight training and endurance running. Soy-PS, in a dose dependent manner (400 mg), has been reported to be an effective supplement for combating exercise-induced stress by blunting the exercise-induced increase in cortisol levels.[4] PS supplementation promotes a desirable hormonal balance for athletes and might attenuate the physiological deterioration that accompanies overtraining and/or overstretching.[5] In recent studies, PS has been shown to enhance mood in a cohort of young people during mental stress and to improve accuracy during tee-off by increasing the stress resistance of golfers.[6]

[edit] Attention-deficit hyperactivity disorder

First pilot studies indicate that PS supplementation might be beneficial for children with attention-deficit hyperactivity disorder.[7][8]

[edit] Safety

Traditionally, PS supplements were derived from bovine cortex (BC-PS); however, due to the potential transfer of infectious diseases, soy-derived PS (S-PS) has been established as a potential safe alternative. Soy-derived PS is Generally Recognized As Safe (GRAS) and is a safe nutritional supplement for older persons if taken up to a dosage of 200 mg three times daily. [9] Phosphatidylserine has been shown to reduce specific immune response in mice. [10][11]

[edit] Dietary sources

PS can be found in meat, but is most abundant in the brain and in innards such as liver and kidney. Only small amounts of PS can be found in dairy products or in vegetables, with the exception of white beans.

Table 1. PS content in different foods.[12]

FoodPS Content in mg/100

g

Bovine brain 713

Atlantic mackerel 480

Chicken heart 414

Atlantic herring 360

Eel 335

Offal (average value) 305

Pig's spleen 239

Pig's kidney 218

Tuna 194

Chicken leg, with skin, without bone

134

Chicken liver 123

White beans 107

Soft-shell clam 87

Chicken breast, with skin 85

Mullet 76

Veal 72

Beef 69

Pork 57

Pig's liver 50

Turkey leg, without skin or bone 50

Turkey breast without skin 45

Crayfish 40

Cuttlefish 31

Atlantic cod 28

Anchovy 25

Whole grain barley 20

European hake 17

European pilchard (sardine) 16

Trout 14

Soy lecithin 10-20[citation needed]

Rice (unpolished) 3

Carrot 2

Ewe's Milk 2

Cow's Milk (whole, 3.5% fat) 1

Potato 1

The average daily PS intake from the diet in Western countries is estimated to be 130 mg.

[edit] Applications

[edit] Research

Annexin-A5 is a naturally-occurring protein with avid binding affinity for PS. Labeled-annexin-A5 enables visualization of cells in the early- to mid-apoptotic state in vitro or in vivo. Another PS binding protein is Mfge8.

[edit] Tumors

Technetium-labeled annexin-A5 enables distinction between malignant and benign tumours whose pathology includes a high rate of cell division and apoptosis in malignant compared with a low rate of apoptosis in benign tumors.

GalactolipidFrom Wikipedia, the free encyclopedia

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General chemical structure of a monogalactosyl diacylglycerol (MGDG), a prevalent type of galactolipid. R1 and R2 are fatty chains.

Galactolipids are a type of glycolipid whose sugar group is galactose. They're different from glycosphingolipids in that they do not have nitrogen in their composition.[1]

They are the main part of plant membrane lipids where they substitute phospholipids to conserve phosphate for other essential processes. These chloroplast membranes contain a high quantity of monogalactosyldiacylglycerol (MGDG) and digalactosyldiacylglycerol (DGDG).

They probably also assume a direct role in photosynthesis, as they have been found in the X-ray structures of photosynthetic complexes.[2]

The galactolipid galactocerebroside (GalC) and its sulfated derivative sulfatide is also in abundance present (together with a small group of proteins) in myelin, the membrane around the axons in the nervous system of vertebrates.[3]

SulfolipidFrom Wikipedia, the free encyclopedia

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Chemical structure of sulfoquinovosyl distearoylglycerol, a type of sulfoquinovosyl diacylglycerol

Sulfolipids are a class of lipids which possess a sulfur-containing functional group. One of the most common consituents of sulfolipids is sulfoquinovose, which is acylated to form sulfoquinovosyl diacylglycerols. In plants, sulfolipids are important intermediates in the sulfur cycle.[1]

CardiolipinFrom Wikipedia, the free encyclopedia

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Cardiolipin

Cardiolipin (alternate image)

Cardiolipin (IUPAC name "1,3-bis(sn-3’-phosphatidyl)-sn-glycerol") is an important component of the inner mitochondrial membrane, where it constitutes about 20% of the total lipid composition. The name ‘cardiolipin’ is derived from the fact that it was first found in animal hearts. It was first isolated from beef heart in the early 1940s[1]. In mammalian cells, cardiolipin (CL) is found almost exclusively in the inner mitochondrial membrane where it is essential for the optimal function of numerous enzymes that are involved in mitochondrial energy metabolism.

Contents[hide]

1 Structure 2 Metabolism and catabolism

o 2.1 Metabolism 2.1.1 Eukaryotic pathway 2.1.2 Prokaryotic pathway

o 2.2 Catabolism 3 Functions

o 3.1 Regulates aggregate structures o 3.2 Helps to build quaternary structure o 3.3 Triggers apoptosis o 3.4 Serves as proton trap for oxidative phosphorylation o 3.5 Other functions

4 Clinical significance o 4.1 Barth syndrome o 4.2 Parkinson's disease and Alzheimer’s disease o 4.3 Nonalcoholic fatty liver disease and heart failure o 4.4 Tangier disease o 4.5 Diabetes o 4.6 Antiphospholipid syndrome o 4.7 Syphilis o 4.8 HIV-1 o 4.9 Cancer

5 Consumer Product Use o 5.1 Beauty and Image

6 See also 7 References 8 External links

[edit] Structure

Cardiolipin in animal tissues

Cardiolipin (CL) is a kind of diphosphatidylglycerol lipid. Two phosphatidylglycerols connect with a glycerol backbone in the center to form a dimeric structure. So it has four alkyl groups and potentially carries two negative charges. As there are four distinct alkyl chains in cardiolipin, the potential for complexity of this molecule species is enormous. However, in most animal tissues, cardiolipin contains 18-carbon fatty alkyl chains with 2 unsaturated bonds on each of them[2]. It has been proposed that the (18:2)4 acyl chain configuration is an important structural requirement for the high affinity of CL to inner membrane proteins in mammalian mitochondria[3].However, studies with isolated enzyme preparations indicate that its importance may vary depending on the protein examined.

Since there are two phosphates in the molecule, each of them can catch one proton. Although it has a symmetric structure, the two phosphates have very different levels of acidity: pK1 =3 and pK2 > 7.5. So, under normal physiological conditions (wherein pH is around 7), the molecule may carry only one negative charge. The hydroxyl groups (–OH and –O-) on phosphate would form a stable intramolecular hydrogen bond with the centered glycerol’s hydroxyl group, thus forming a bicyclic resonance structure. This structure traps one proton, which is quite helpful for oxidative phosphorylation.

As the head group forms such compact bicycle structure, the head group area is quite small relative to the big tail region consist of 4 acyl chains. Based on this special structure, the fluorescent mitochondrial indicator, nonyl acridine orange (NAO) was introduced in 1982[4], and was later found to target mitochondria by binding to CL. NAO has a very large head and small tail structure which can compensate with cardiolipin’s small tail large head structure, and arrange in a highly ordered way[5].Several studies were published utilizing NAO both as a quantitative mitochondrial indicator and an indicator of CL content in mitochondria. However, it is found that NAO was influenced by membrane potential and/or the spatial arrangement of CL[6][7][8].so it's not proper to use NAO for CL or mitochondria quantitative studies of intact respiring mitochondria. But NAO still represents a simple method of assessing CL content.

Cardiolipin bicyclic structureStructure of NAO

NAO & CL arranged in a highly ordered way

[edit] Metabolism and catabolism

Cardiolipin synthesis in eukaryotes

[edit] Metabolism

[edit] Eukaryotic pathway

In eukaryotes such as yeasts, plants and animals, the synthesis processes are believed to happen in mitochondria. The first step is the acylation of glycerol-3-phosphate by a glycerol-3-phosphate acyltransferase. Then acylglycerol-3-phosphate can be acylated to form a phosphatidic acid (PA). With the help of the enzyme CDP-DAG synthase (phosphatidate cytidylyltransferase), PA is converted into cytidinediphosphate-diacylglycerol (CDP-DAG). The following step is conversion of CDP-DAG to phosphatidylglycerol phosphate (PGP) by the enzyme PGP synthase, followed by dephosphorylation to form PG. Finally, a molecule of CDP-DAG is bind to PG to form one molecule of cardiolipin, catalyzed by enzyme cardiolipin synthase (CLS)[9].

[edit] Prokaryotic pathway

In prokaryotes such as bacteria, diphosphatidylglycerol synthase catalyses a transfer of the phosphatidyl moiety of one phosphatidylglycerol to the free 3'-hydroxyl group of another, with the elimination of one molecule of glycerol, via the action of an enzyme related to phospholipase D. The enzyme can operate in reverse under some physiological conditions to remove cardiolipin.

[edit] Catabolism

Catabolism of cardiolipin may happen by the catalysis of phospholipase A2 (PLA) to remove fatty acyl groups. Phospholipase D (PLD) in the mitochondrion hydrolyses cardiolipin to phosphatidic acid[10].

[edit] Functions

[edit] Regulates aggregate structures

respiratory electron transfer of Complex IV

Because of cardiolipin’s unique bicyclic structure, a change in pH and the presence of divalent cations can induce a structural change. CL shows a great variety of forms of aggregates. It is found that in the presence of Ca2+ or other divalent cations, CL can be induced to have a lamellar-to-hexagonal (La-HII) phase transition. And it is believed to have a close connection with membrane fusion [11] [12].

[edit] Helps to build quaternary structure

The enzyme cytochrome c oxidase or Complex IV is a large transmembrane protein complex found in bacteria and the mitochondrion. It is the last enzyme in the respiratory electron transport chain of mitochondria (or bacteria) located in the mitochondrial (or bacterial) membrane. It receives an electron from each of four cytochrome c molecules, and transfers them to one oxygen molecule, converting molecular oxygen to two molecules of water. Complex IV has been shown to require two associated CL molecules in order to maintain its full enzymatic function. Cytochrome bc1(Complex III) also needs cardiolipin to maintain its quaternary structure and to maintains its functional role[13]. Complex V of the oxidative phosphorylation machinery also displays high binding affinity for CL, binding four molecules of CL per molecule of complex V[14].

mechanism of how CL trigger apotosis

[edit] Triggers apoptosis

During apoptosis, cytochrome c (cyt c) is released from the intermembrane spaces of mitochondria into the cytosol. Cyt c can then bind to the IP3 receptor on ER, stimulating calcium release, which then reacts back to cause the release of cyt c. When the calcium concentration reaches a toxic level, this causes cell death. Cytochrome c is thought to play a role in apoptosis via the release of apoptotic factors from the mitochondria [15] . A cardiolipin-specific oxygenase produces CL hydroperoxides which can result in the conformation change of the lipid. The oxidized CL the transfers from the inner membrane to the outer membrane, and then helps to form a permeable pore which releases cyt c.

CL serves as a proton trap in oxidative phosphorylation

[edit] Serves as proton trap for oxidative phosphorylation

During the oxidative phosphorylation process catalyzed by Complex IV, large quantities of protons are transferred from one side of the membrane to another side causing a large pH change. CL is suggested to function as a proton trap within the mitochondrial membranes, thereby strictly localizing the proton pool and minimizing the changes in pH in the mitochondrial intermembrane space.

This function is due to CL’s unique structure. As stated above, CL can trap a proton within the bicyclic structure while carrying a negative charge. Thus, this bicyclic structure can serve as an electron buffer pool to release or absorb protons to maintain the pH near the membranes[5].

[edit] Other functions

Cholesterol translocation from outer to the inner membrane of mitochondrial Activates mitochondrial cholesterol side-chain cleavage Import protein into mitochondrial matrix Anticoagulant function

[edit] Clinical significance

[edit] Barth syndrome

Barth syndrome is a rare genetic disorder that was recognised in the 1970s to cause infantile death. It has a mutation in the gene coding for tafazzin, an enzyme involved in the biosynthesis of cardiolipin. Tafazzin is an indispensable enzyme to synthesize cardiolipin in eukaryotes involved in the remodeling of CL acyl chains by transferring linoleic acid from PC to monolyso-CL[16].Mutation of tafazzin would cause not enough cardiolipin synthesis and thus cause not enough ATP production. Girls heterozygous for the trait are unaffected. Sufferers of this condition have mitochondria that are abnormal, and they cannot sustain adequate production of ATP. Cardiomyopathy and general weakness is common to these patients. Cardiolipin treats the symptoms of Barth syndrome and prevents infections.

[edit] Parkinson's disease and Alzheimer’s disease

Oxidative stress and lipid peroxidation are believed to be important contributing factors leading to neuronal loss and mitochondrial dysfunction in the substantia nigra in Parkinson's disease, and may play an early role in the pathogenesis of Alzheimer’s disease [17] [18] . It is reported that CL content in the brain would decrease with aging[19]. and a recently study on rat brain shows it’s resulted from lipid peroxidation in mitochondria exposed to free radical stress. Another study also shows that CL biosynthesis pathway of CL may be selectively impaired and cause 20% reduction and composition change of CL content[20]. And it’s also associated with a 15% reduction in linked complex I/III activity of the electron transport chain, which though to be a critical factor in the development of Parkinson's disease[21].

[edit] Nonalcoholic fatty liver disease and heart failure

Recently, it is reported that in non-alcoholic fatty liver disease [22] and heart failure [23] ， decreased CL levels and change in acyl chain composition are also observed in the mitochondrial dysfunction. However, the role of CL in aging and ischemia/reperfusion is still controversial.

[edit] Tangier disease

Tangier disease is also linked to CL abnormalities. Tangier disease is characterized by very low blood plasma levels of high-density lipoprotein cholesterol, accumulation of cholesteryl esters in tissues and an increased risk for developing cardiovascular disease [24] . Unlike Barth syndrome, Tangier disease is mainly caused by abnormal enhanced production of CL. Studies show that there are three to fivefold increase of CL level in Tangier disease[25]. Because increased CL levels would enhance cholesterol oxidation, and then the formation of oxysterols would consequently increase cholesterol efflux. This process could function as an escape mechanism to remove excess cholesterol from the cell.

[edit] Diabetes

Heart disease hits people with diabetes twice as often as people without diabetes. In those with diabetes, cardiovascular complications occur at an earlier age and often result in premature death, making heart disease the major killer of diabetic people. Cardiolipin has recently been found to be deficient in the heart at the earliest stages of diabetes, possibly due to a lipid-digesting enzyme that becomes more active in diabetic heart muscle[26].

[edit] Antiphospholipid syndrome

Patients with anti-cardiolipin antibodies (Antiphospholipid syndrome) can have recurrent thrombotic events even early in their mid- to late-teen years. These events can occur in vessels in which thrombosis may be relatively uncommon, such as the hepatic or renal veins. These antibodies are usually picked up in young women with recurrent spontaneous abortions. In anti-cardiolipin-mediated autoimmune disease, there is a dependency on the apolipoprotein H for recognition.[27]

[edit] Syphilis

Cardiolipin from a cow heart is used as an antigen in the Wassermann test for syphilis. Anti-cardiolipin antibodies can also be increased in numerous other conditions, including systemic lupus erythematosus, malaria and tuberculosis, so this test is not specific.

[edit] HIV-1

Human immunodeficiency virus-1 (HIV-1) has infected more than 60 million people worldwide. Developing effective antibodies for HIV-1 becomes a hotspot in scientific research. HIV-1 envelope glycoprotein contains at least four sites for neutralizing antibodies. Among these sites, the membrane-proximal region (MPR) is particularly attractive as an antibody target because it facilitates viral entry into T cells and is highly conserved among viral strains[28] .However, it is

found that two antibodies directed against 2F5, 4E10 in MPR react with self-antigens, including cardiolipin. Thus, it’s difficult for such antibodies to be elicited by vaccination[29] .

[edit] Cancer

It was first proposed by Otto Heinrich Warburg that cancer originated from irreversible injury to mitochondrial respiration, but the structural basis for this injury has remained elusive. Since cardiolipin is an important phospholipid found almost exclusively in the inner mitochondrial membrane and very essential in maintaining mitochondrial function, it is suggested that abnormalities in CL can impair mitochondrial function and bioenergetics. A study[30] published in 2008 on mouse brain tumors supporting Warburg’s cancer theory shows major abnormalities in CL content or composition in all tumors.

[edit] Consumer Product Use

[edit] Beauty and Image

Amway Corporation began selling a skin creme (called Creme LuXury) in the United States in 2010, identifying cardiolipin as the primary active ingredient. Other manufacturers may also have similar products, or will follow with similar products. These products have a high-end price and performance.

[edit] See also

Phosphatidylglycerol

GlycerolFrom Wikipedia, the free encyclopedia

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"Glycerine" and "Glycerin" redirect here. For the Bush song, see Glycerine (song).

Glycerol

IUPAC name [hide]

propan-1,2,3-triol

Other names[hide]

glyceringlycerine

propane-1,2,3-triol1,2,3-propanetriol

1,2,3-trihydroxypropaneglyceritol

glycyl alcohol

Identifiers

CAS number 56-81-5

PubChem 753

ChemSpider 733

UNII PDC6A3C0OX

KEGG D00028

ChEMBL CHEMBL692

ATC code A06 AG04 ,A06 AX01 , QA16 QA03

SMILES

[show]InChI

[show]

Properties

Molecular formula C3H5(OH)3

Molar mass 92.09382 g/mol

Appearanceclear, colourless liquidhygroscopic

Odor odourless

Density 1.261 g/cm³

Melting point17.8 °C (64.2°F)

Boiling point290 °C (554°F)[1]

Refractive index (nD) 1.4746

Viscosity 1.2 Pa·s

Hazards

MSDS External MSDS

NFPA 704 1

1

0

Flash point160 °C (closed cup)176 °C (open cup)

Supplementary data page

Structure andproperties

n, εr, etc.

Thermodynamicdata

Phase behaviourSolid, liquid, gas

Spectral data UV, IR, NMR, MS

(what is this?) (verify)Except where noted otherwise, data are given for materials

in their standard state (at 25 °C, 100 kPa)

Infobox references

Glycerol (or glycerin, glycerine) is a simple polyol compound. It is a colourless, odourless, viscous liquid that is widely used in pharmaceutical formulations. Glycerol has three hydrophilic hydroxyl groups that are responsible for its solubility in water and its hygroscopic nature. The glycerol backbone is central to all lipids known as triglycerides. Glycerol is sweet-tasting and of low toxicity.

Contents[hide]

1 Production 2 Applications

o 2.1 Foods industry o 2.2 Pharmaceutical and personal care applications o 2.3 Botanical extracts o 2.4 Anti-freeze o 2.5 Chemical intermediate

3 Metabolism 4 Historical cases of contamination with diethylene glycol 5 Additional physical properties 6 See also 7 References 8 External links

[edit] Production

Glycerol forms the backbone of triglycerides, and can be produced by saponification of fats, e.g. a byproduct of soap-making.

It also is a byproduct of the production of biodiesel via transesterification. Triglycerides (1) are reacted with an alcohol such as ethanol (2) with catalytic base to give ethyl esters of fatty acids (3) and glycerol (4):

Glycerol is also produced by various routes from propylene. The epichlorohydrin process is the most important; it involves the chlorination of propylene to give allyl chloride, which is oxidized with hypochlorite to dichlorohydrins, which reacts with a strong base to give epichlorohydrin. Epichlorohydrin is then hydrolyzed to give glycerol.[2]

Because of the emphasis on biodiesel, where Glycerol is a waste product, the market for glycerol is depressed, and the old epichlorohydrin process for glycerol synthesis is no longer economical on a large scale. Only one producer for synthetic glycerol is left, because high-quality glycerol is needed in highly sensitive pharmaceutical, technical and personal care applications. Raw materials used to make glycerol and glycerin include animal fats, such as beef tallow, and vegetable oils, such as coconut and soybean.[3] Approximately 950,000 tons per annum are produced in the USA and Europe; 350,000 tons of glycerol were produced per year in the United States alone from 2000-2004.[4] Production will increase as the EU directive 2003/30/EC is implemented, which requires the replacement of 5.75% of petroleum fuels with biofuel across all Member States by 2010. It is projected that by the year 2020, production will be six times more than demand.[2]

[edit] ApplicationsThis section needs additional citations for verification.Please help improve this article by adding reliable references. Unsourced material may be challenged and

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[edit] Foods industry

In foods and beverages, glycerol serves as a humectant, solvent and sweetener, and may help preserve foods. It is also used as filler in commercially prepared low-fat foods (e.g., cookies), and as a thickening agent in liqueurs. Glycerol and water are used to preserve certain types of leaves. As a sugar substitute, it has approximately 27 calories per teaspoon and is 60 percent as sweet as sucrose. Although it has about the same food energy as table sugar, it does not raise blood sugar levels, nor does it feed the bacteria that form plaques and cause dental cavities. As a food additive, glycerol is labeled as E number E422.

Glycerol is also used to manufacture mono- and di-glycerides for use as emulsifiers, as well as polyglycerol esters going into shortenings and margarine.

It is also used as a humectant (along with propylene glycol labelled as E1520 and/or E422) in the production of snus, a Swedish style smokeless tobacco product.

As used in foods, glycerol is categorized by the American Dietetic Association as a carbohydrate. The U.S. FDA carbohydrate designation includes all caloric macronutrients excluding protein and fat. Glycerin has a caloric density similar to table sugar, but a lower glycemic index and different metabolic pathway within the body, so some dietary advocates accept glycerin as a sweetener compatible with low carbohydrate diets.

[edit] Pharmaceutical and personal care applications

Glycerol is used in medical and pharmaceutical and personal care preparations, mainly as a means of improving smoothness, providing lubrication and as a humectant. It is found in allergen immunotherapies, cough syrups, elixirs and expectorants, toothpaste, mouthwashes, skin care products, shaving cream, hair care products, soaps and water based personal lubricants. In solid dosage forms like tablets, Glycerol is used as a tablet holding agent. For human consumption, glycerol is classified by the U.S. FDA among the sugar alcohols as a caloric macronutrient.

Glycerol is a component of glycerin soap, which is made from denatured alcohol, glycerol, sodium castorate (from castor), sodium cocoate, sodium tallowate, sucrose, and water. Sometimes one adds sodium laureth sulfate, or essential oils for fragrance. This kind of soap is used by people with sensitive, easily-irritated skin because it prevents skin dryness with its moisturizing properties. It draws moisture up through skin layers and slows or prevents excessive drying and evaporation. It is possible to make glycerol soap at home.

Used as a laxative when introduced into the rectum in suppository or small-volume (2to10ml)(enema) form; irritates the anal mucosa and induces a hyperosmotic effect.

Topical pure or nearly pure glycerol is an effective treatment for psoriasis, burns, bites, cuts, rashes, bedsores, and calluses. It can be used orally to eliminate halitosis, as it is a contact

bacterial desiccant. The same property makes it very helpful with periodontal disease; it penetrates biofilm quickly and eliminates bacterial colonies.

[edit] Botanical extracts

When utilized in 'tincture' method extractions specifically, as a 10% solution, glycerol prevents tannins from precipitating in ethanol extracts of plants (tinctures). It is also used as a substitute for ethanol as a solvent in preparing herbal extractions. It is less extractive when utilized in tincture methodology and is approximately 30% more slowly absorbed by the body resulting in a much lower glycemic load. Fluid extract manufacturers often extract herbs in hot water before adding glycerin to make glycerites.[5][6][7]

When used as a primary true alcohol-free botanical extraction solvent in innovative non-tincture based methodologies, glycerol has been shown, both in literature and through extraction applications, to possess a high degree of extractive versatility for botanicals including removal of numerous constituents and complex compounds, often equal to or greater than that for ethanol. Glycerol is a stable preserving agent for botanical extracts that, when utilized in proper concentrations in an extraction solvent base, not only preserves safety and purity but does not allow inverting or REDOX of a finished extract's constituents over many years. Both Glycerol and ethanol are viable preserving agents. Glycerol is bacteriostatic in its action, and ethanol is bactericidal in its action. However, Glycerol possesses no secondary denaturing or inert rendering effects on a botanical extract's constituents, hence, Glycerol's preferred use in making many botanical extracts and use in pharmaceuticals where this quality is required.[8][9][10]

[edit] Anti-freeze

Like ethylene glycol and propylene glycol, glycerol dissolved in water disrupts the hydrogen bonding between water molecules such that the mixture cannot form a stable crystal structure unless the temperature is significantly lowered. The minimum freezing point temperature is at about -36 °F / -37.8 °C corresponding to 60-70 % glycerol in water.[11]

Glycerol was historically used as an anti-freeze for automotive applications before being replaced by ethylene glycol, which has a lower freezing point. While, the minimum freezing point of a glycerol-water mixture is higher than an ethylene-glycol mixture, glycerol is not toxic and is being re-examined for use in automotive applications.[12]

In the laboratory, glycerol is a common component of solvents for enzymatic reagents stored at temperatures below 0 °C due to the depression of the freezing temperature of solutions with high concentrations of glycerol. It is also dissolved in water to reduce damage by ice crystals to laboratory organisms that are stored in frozen solutions, such as bacteria, nematodes, and fruit flies.

[edit] Chemical intermediate

Glycerol is used to produce nitroglycerin, or glycerol-trinitrate (GTN), which is an essential ingredient of smokeless gunpowder and various explosives such as dynamite, gelignite and

propellants like cordite. Reliance on soap-making to supply co-product glycerine made it difficult to increase production to meet wartime demand. Hence, synthetic glycerin processes were national defence priorities in the days leading up to World War II. GTN is commonly used to relieve angina pectoris, taken in the form of sub-lingual tablets, or as an aerosol spray.

A great deal of research is being conducted to try to make value-added products from crude glycerol (typically containing 20 % water and residual esterification catalyst) obtained from biodiesel production, as an alternative to disposal by incineration.

Hydrogen gas production unit[13]

Glycerine acetate (as a potential fuel additive)[14]

Conversion to propylene glycol [15] Conversion to acrolein [16] [17] Conversion to ethanol [18] Conversion to epichlorhydrin,[19] a raw material for epoxy resins

[edit] Metabolism

Glycerol is a precursor for synthesis of triacylglycerols and of phospholipids in the liver and adipose tissue. When the body uses stored fat as a source of energy, glycerol and fatty acids are released into the bloodstream. In some organisms, the glycerol component can be converted into glucose by the liver and, thus, provide energy for cellular metabolism . In animals, wherein glycerol is derived from glucose (e.g., humans and other mammals), glycerol is sometimes not considered a true gluconeogenic substrate, as it cannot be used to generate new glucose.[citation

needed]

Before glycerol can enter the pathway of glycolysis or gluconeogenesis (depending on physiological conditions), it must be converted to their intermediate glyceraldehyde 3-phosphate in the following steps:

GlycerolGlycerol kinase

Glycerol-3-phosphate

Glycerol-3-phosphate

dehydrogenase

Dihydroxyacetone phosphate

Triosephosphate isomerase

Glyceraldehyde 3-phosphate

ATP ADP FAD FADH2

NAD+ NADH

The enzyme glycerol kinase is present only in the liver. In adipose tissue, glycerol 3-phosphate is obtained from dihydroxyacetone phosphate (DHAP) with the enzyme glycerol-3-phosphate dehydrogenase.

[edit] Historical cases of contamination with diethylene glycol

On May 4, 2007, the US Food and Drug Administration advised all US makers of medicines to test all batches of glycerine for the toxic diethylene glycol.[20] This follows an occurrence of 100 fatal poisonings in Panama resulting from a Chinese factory deliberately falsifying records in order to export the cheaper diethylene glycol as the more expensive glycerol.[21] Glycerine and diethylene glycol are similar in appearance, smell, and taste. The US Federal Food, Drug, and Cosmetic Act was passed following the 1937 "Elixir Sulfanilamide" incident of poisoning caused by diethylene glycol contamination of medicine.

[edit] Additional physical properties

Its surface tension is 64.00 mN/m at 20 °C , and it has a temperature coefficient of -0.0598 mN/(m K).[22]

[edit] See also

Biodiesel by-product Epichlorohydrin Nitroglycerin Oleochemicals Saponification /Soap making Sugar alcohol Transesterification