21 21-1 © 2006 Thomson Learning, Inc. All rights reserved General, Organic, and Biochemistry, 8e Bettelheim, Brown, Campbell, & Farrell

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21-1© 2006 Thomson Learning, Inc.All rights reserved

General, Organic, General, Organic, and Biochemistry, 8eand Biochemistry, 8e

Bettelheim, Brown,Bettelheim, Brown,

Campbell, & FarrellCampbell, & Farrell

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Chapter 21Chapter 21

LipidsLipids

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LipidsLipids• Lipids:Lipids: a heterogeneous class of naturally occurring organic compounds classified together on the basis of common solubility properties.• insoluble in water, but soluble in organic solvents including diethyl ether, dichloromethane, and acetone

• Lipids include:• fatty acids, triglycerides, sphingolipids, phosphoacylglycerols, and glycolipids.

• lipid-soluble vitamins.• prostaglandins, leukotrienes, and thromboxanes.

• cholesterol, steroid hormones, and bile acids.

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TriglycerideTriglyceride• Triglyceride:Triglyceride: an ester of glycerol with three fatty acids.

O

CH2OCR

CH2OCR''

R'COCH

OO

1. NaOH, H2O

2. HCl, H2O CH2OH

CH2OH

HOCH

RCOOH

R'COOH

R''COOH

A triglyceride 1,2,3-Propanetriol(Glycerol, glycerin)

+

Fatty acids

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TriglyceridesTriglycerides• Physical properties depend on the fatty acid components:• Melting points of fatty acids increases as the number of carbons in the hydrocarbon chains increases and as the number of double bonds decreases.

• Triglycerides rich in unsaturated fatty acids are generally liquid at room temperature and are called oilsoils

• Triglycerides rich in saturated fatty acids are generally semisolids or solids at room temperature and are called fatsfats.

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TriglyceridesTriglycerides• The lower melting points of triglycerides rich in unsaturated fatty acids are related to differences in their three-dimensional shape.• Hydrocarbon chains of saturated fatty acids can lie parallel with strong London dispersion forces between their chains; they pack into well-ordered, compact crystalline forms and melt above room temperature

• Because of the cis configuration of the double bonds in unsaturated fatty acids, their hydrocarbon chains have a less ordered structure and London dispersion forces between them are weaker; these triglycerides have melting points below room temperature.

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HydrogenationHydrogenation• Hardening: reduction of some or all of the carbon-carbon double bonds of an unsaturated triglyceride using H2/transition metal catalyst.• In practice, the degree of hardening is carefully controlled to produce fats of a desired consistency.

• The resulting fats are sold for kitchen use (Crisco, Spry, Dexo, and others).

• Margarine and other butter substitutes are produced by partial hydrogenation of polyunsaturated oils derived from corn, cottonseed, peanut, and soybean oils.

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Complex LipidsComplex Lipids• Phospholipids

• contain an alcohol, two fatty acids, and a phosphate ester.

• In glycerophospholipids, the alcohol is glycerol.

• In sphingolipids, the alcohol is sphingosine.

• Glycolipids• Complex lipids that contain a carbohydrate.

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Complex LipidsComplex Lipids• Figure 21.1 Schematic diagram of simple and complex lipids.

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MembranesMembranes• Complex lipids form the membranes around cells and small structures within cells.

• In aqueous solution, complex lipids spontaneously form into a lipid bilayer, with a back-to-back arrangement of lipid monolayers.• Polar (hydrophilic) head groups are in contact with the aqueous environment.

• Nonpolar (hydrophobic) tails are buried within the bilayer and shielded from the aqueous environment.

• The major force driving the formation of lipid bilayers is hydrophobic interaction.

• The arrangement of hydrocarbon tails in the interior can be rigid (if rich in saturated fatty acids) or fluid (if rich in unsaturated fatty acids).

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Fluid Mosaic ModelFluid Mosaic Model

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GlycerophospholipidsGlycerophospholipids• GlycerophospholipidsGlycerophospholipids are the second most abundant group of naturally occurring lipids.• They are also called phosphoglycerides.• Found almost exclusively in plant and animal membranes, which typically consist of 40% -50% phosphoacylglycerols and 50% - 60% proteins.

• The most abundant glycerophospholipids are derived from phosphatidic acid, a molecule in which glycerol is esterified with two molecules of fatty acid and one of phosphoric acid.

• The three most abundant fatty acids in phosphatidic acids are palmitic (16:0), stearic (18:0), and oleic (18:1).

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GlycerophospholipidsGlycerophospholipids• A phosphatidic acid

• The fatty acid on carbon 2 of glycerol is always unsaturated.

• Further esterification with a low-molecular-weight alcohol (next screen) gives a glycerophospholipid.

CH2

CH

CH2-O-P-O-

O

O

O

Oglycerol

palmitic acid

oleic acid

O

O-

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GlycerophospholipidsGlycerophospholipids

HOHO

OHOH

OH

OH

NH3+

HOCH2CHCOO-

HOCH2CH2N(CH3)3

HOCH2CH2NH2

inositol phosphatidylinositol

Name and FormulaName of Glycerophospholipid

ethanolamine

+choline lecithin

cephalin

serine cephalin

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GlycerophospholipidsGlycerophospholipids• a lecithina lecithin

CH2

CH

CH2

O

O

O

O

O P OCH2CH2N(CH3)3

O

O-

+

palmitic acid

linolenic acid

glycerol

choline

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SphingolipidsSphingolipids• Found in the coatings of nerve axons (myelin).• Contain the long-chain aminoalcohol, sphingosine, from which this class of compounds in named.

OH

(CH2)12CH3

HO

NH2

SphingosineOH

(CH2)12CH3

HO

NHCR

A ceramide(an N-acylsphingosine)

OPOCH2CH2N(CH3)3

(CH2)12CH3

HO

NHCR

A sphingomyelinO

O-+

O O

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GlycolipidsGlycolipids• GlycolipidGlycolipid:: a complex lipid that contains a carbohydrate.• The carbohydrate is either glucose or galactose.

• The cerebrosides are ceramide mono- or oligosaccharides.

O

(CH2)12CH3

HO

NHCR

O

H

HO

H

HO

H

HOH

H

OHO

a-glycosidic bond

a unit of -D-glucopyranose

a ceramide

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SteroidsSteroids• SteroidsSteroids:: a group of plant and animal lipids that have this tetracyclic ring structure.

A B

C D

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CholesterolCholesterol• Cholesterol is the most abundant steroid in the human body, and also the most important.• It is a component in plasma membranes in all animal cells.

• It is the precursor of all steroid hormones and bile acids.

HO

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LipoproteinsLipoproteins• Cholesterol, along with fats, are transported by lipoproteins

Lipoprotein

Composition (% dry weight)

ProteinsCholesteroland esters

Phospho-lipids

Tri-glycerides

High-densitylipoprotein (HDL)

Low-densitylipoprotein (LDL)

Very-low densitylipoprotein (VLDL)

Chylomicrons

33 30 29 8

25 50 21 4

10 22 18 50

1-2 8 7 84

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LipoproteinsLipoproteins• Figure 21.5 Schematic of a low-density lipoprotein.

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Cholesterol TransportCholesterol Transport• Transport of cholesterol from the liver starts with VLDL.

• VLDL is carried in the serum.• As fat is removed, its density increases and it becomes LDL; LDL stays in the plasma for about 2.5 days.

• LDL carries cholesterol to cells, where specific LDL receptors bind it.

• After binding, LDL is taken into cells where enzymes liberate free cholesterol and cholesteryl esters.

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Cholesterol TransportCholesterol Transport• High-density lipoproteins (HDL) transport cholesterol from peripheral tissues to the liver and also transfer cholesterol to LDL.

• While in the serum, free cholesterol in HDL is converted to cholesteryl esters.

• In the liver, HDL binds to the liver cell surface and transfers its cholesteryl esters to the cell.

• These esters are used for the synthesis of steroid hormones and bile acids.

• After LDL has delivered its cholesteryl esters to liver cells, it reenters circulation.

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Levels of LDL and HDLLevels of LDL and HDL• Most of the cholesterol is carried by LDL.• Normal plasma levels are 175 mg/100 mL.• If there are sufficient LDL receptors on the surface of cells, LDL is removed from circulation and its concentration in blood plasma drops.

• The number of LDL receptors is controlled by a feedback mechanism.

• When the concentration of cholesterol inside cells is high, the synthesis of LDL receptors is suppressed.

• In the disease called hypercholesterolemia, there are not enough LDL receptors and plasma levels of cholesterol may be as high as 680 mg/100 mL.

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Levels of LDL and HDLLevels of LDL and HDL• These high levels of cholesterol can cause premature atherosclerosis and heart attacks.

• In general, high LDL means high cholesterol content in the plasma because LDL cannot get into cells.

• Therefore, high LDL together with low HDL is a symptom of faulty cholesterol transport and a warning of possible atherosclerosis.

• The serum cholesterol level controls cholesterol synthesis in the liver.

• When serum cholesterol is high, its synthesis in the liver is low, and vice versa.

• The commonly used statin drugs inhibit the synthesis of cholesterol by blocking HMG-CoA reductase.

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Steroid HormonesSteroid Hormones• Androgens:Androgens: male sex hormones

• synthesized in the testes• responsible for the development of male secondary sex characteristics

AndrosteroneTestosteroneO

OH

H3C

H3C H3C

H3C

O

HO

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Steroid HormonesSteroid Hormones• Among the synthetic anabolic steroids are:

O

H3C

H3C

MethandienoneO

CH3

H3CH3C

OHOH

CH3

MethenoloneO

H3C

H3C O

4-Androstene-3,17-dione

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Steroid HormonesSteroid Hormones• Estrogens:Estrogens: female sex hormones

• synthesized in the ovaries from progesterone• responsible for the development of female secondary sex characteristics and control of the menstrual cycle

Progesterone Estradiol

H3C

H3C

C=O

O

CH3

OH

HO

H3Cseveralsteps

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Steroid HormonesSteroid Hormones• Progesterone-like analogs are used in oral contraceptives:

H3C

O

OHC CH

H3C

O

OHC CCH3

NH3C

CH3

"Nor" refers tothe absence of a methyl group here

Norethindrone

Mifepristone(RU486)

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Steroid HormonesSteroid Hormones• Glucorticoid hormonesGlucorticoid hormones

• synthesized in the adrenal cortex.• regulate metabolism of carbohydrates.• decrease inflammation.• involved in the reaction to stress.

Aldosterone

C=O

CH2OH

O

H

H3C H

H

CHHO

O

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Bile SaltsBile Salts• Bile saltsBile salts, the oxidation products of cholesterol.• synthesized in the liver, stored in the gallbladder, and secreted into the intestine where they emulsify dietary fats and aid in their absorption and digestion

HO

H3C

CH3

H3C

OH

HO NH

O

HO

H3C

CH3

H3C

OH

HO NH

O

SO32-

Glycocholate(from glycine)

Taurocholate(from taurine)

COO-

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ProstaglandinsProstaglandins• Prostaglandins:Prostaglandins: a family of compounds that have the 20-carbon skeleton of prostanoic acid. COOH

2

3

4

5

67

89

2011

1213

1415

1617

1819

1

10

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ProstaglandinsProstaglandins• Prostaglandins are not stored in tissues as such, but are synthesized from membrane-bound 20-carbon polyunsaturated fatty acids in response to specific physiological triggers.• One such polyunsaturated fatty acid is arachidonic acid.

COOH

Arachidonic acid1514

89

11 12

6 5

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ProstaglandinsProstaglandins

15

9 9

11 11

Arachidonic acid

PGF2PGE2

PGG2

Aspirin and other NSAIDs inhibit this enzyme

15

9

11

9

11

15

OOH

COOHO

O

OH

COOH

O

HO

COOH

OH

COOH

2O2

15

cyclooxygenase (COX)

HO

HO

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COX EnzymesCOX Enzymes• The COX (cyclooxygenase) enzyme occurs in two forms:

• COX-1 catalyzes the normal physiological production of prostaglandins.

• COX-2 is responsible for the production of prostaglandins in inflammation.• When a tissue is injured or damaged, special inflammatory cells invade the injured tissue and interact with resident cells, for example, smooth muscle cells.

• This interaction activates COX-2 and prostaglandins are synthesized.

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ThromboxanesThromboxanes• Thromboxanes are also derived from arachidonic acid.• Thromboxane A2 induces platelet aggregation and vasoconstriction.

• Aspirin and other NSAIDs inhibit the synthesis of thromboxanes by inhibiting the COX enzyme.

O

OOH

COOH

Thromboxane A2

189

11 201512

10

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LeukotrienesLeukotrienes• Leukotrienes are also synthesized from arachidonic acid.• They occur mainly in leukocytes.• They produce muscle contractions, especially in the lungs and thereby can cause asthma-like attacks.

• In this regard, they are 100 times more potent than histamine.

• Several recently-developed anti-asthma drugs inhibit the synthesis of leukotrienes.OH OH

COOH

Leukotriene B4

1512

20

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End End Chapter 21Chapter 21

LipidsLipids

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21 21-1 © 2006 Thomson Learning, Inc. All rights reserved General, Organic, and Biochemistry, 8e Bettelheim, Brown, Campbell, & Farrell