LIPIDS

• It is almost impossible to watch TV ads without some company talking about fats and dieting. We’re familiar with that, but we still crave the foods that contain fats and still know very little about them.

1. FATTY ACIDS – LIPID BUILDING BLOCKS

2. TRIACYLGLYCERIDES & PHOSPHOLIPIDS

3. SPHINGOMYELINS (NOT VERY DIFFICULT)

4. CHOLESTEROL & FRIENDS (STEROIDS)

Essential information:Fats are lipids, but NOT ALL LIPIDS ARE FATS. Both substances are soluble in non-polar solvents -- like benzene and xylene (liquids used in organic chemistry). However, the terms lipids and fats have different meanings.

Fats are esters formed from fatty acids and the compound glycerol. Animals use fats for energy storage and insulation.

Lipids are compounds soluble in a non-polar solvents, but they don’t have to be esters.

So a lipid could include stuff like gasoline or jetengine fuel (specially formulated kerosene) oreven be in that material in our bodies that theweight reduction people call “cellulite”(tissue composed of cells full of triacylglerols, a type of fat).

We have to be careful how the terms are used.All the compounds used in this course are allaccurately called lipids.

SOME EXAMPLES OF LIPIDS:

This lipid is a fat.

WHY ARE LIPIDS IMPORTANT?

1. They are a significant source of fuel/ energy.

2. They form borders for cells and within cells.

3. They are sources of hormones & vitamins.

t

TRIACYLGLYEROLS HEART TISSUE OTHER TISSUES (STARVATION) INSULIN DEPENDENT TISSUES (DIABETES)

PHOSPHOLIPIDS FORM/ MAINTAIN PLASMACHOLESTEROL MEMBRANES AND SUB-CELLULAR ORGANELLE BOUNDARIES

CHOLESTEROL PRECURSOR FOR MANY HORMONES

LIPID SOLUBILITY CHARACTERISTICS

IT GOES WITHOUT SAYING THAT LIPIDS ARE SOLUBLEIN NON-POLAR SOLVENTS. THAT IS, THERE IS NO PARTIALCHARGE IN ANY PART OF A LIPID SOLVENT SUCH AS IS FOUND IN WATER.ENERGETICALLY, LIPIDS ARE STABLE INNON-POLAR SOLVENTSAND THEY ARE CALLED “HYDROPHOBIC” – WATER HATING COMPOUNDS.

OF COURSE, THERE ARE EXCEPTIONS. SOME LIPIDS HAVEA PORTION OF THEIR COMPOSITION THAT IS COMPATIBLE WITH WATER (CHARGED REGIONS). SUCHLIPIDS ARE CALLED “AMPHIPATHIC” – DUAL ROLES.

H HO

+d+d

-d

What exactly is a hydrophobic bond?

It is not a true bond, but an associationof non-polar compounds made tominimize their contact with a polarsolvent. This is energetically favorablefor the polar solvent.

It helps if the non-polar compound(such as a lipid) has some hydrophilicregion(s).

The micelle structure to the right is composed of fatty acids in whicha) the alkyl groups are buried inwardb) the carboxyl groups interact with the polar water molecules.

What if there are no hydrophilic regions?

TWO NON-POLAR SOLVENTS ARE SHOWN HERE:

CH3 CH3

HEPTANE

CYCLOHEXANE

TWO PARTIALLY POLAR LIPIDS ARE SHOWN HERE:

PALMITIC ACID OLEIC ACID

POLAR ENDS

Fatty acids: lipid building blocks

• Fatty acids have two parts: a hydrocarbon

tail and a carboxylic head

CH3-CH2-CH2-CH2-CH2-CH2-CH2-CH2-CH2-CH2-CH2-COO- H+

DODECANOIC ACID or LAURIC ACID Greek = 12 ( = dodekanos dodekanos)Latin = laurel plant (laurus)

FATTY ACID FACTS:

• FA have both IUPAC (systematic) &

common names.• FA partially deionize.• Most biological FA are 12-24 carbons long.• FA are either completely saturated or have

one or more double bonds.

• carbon length - melting point

• unsaturation - melting point

Here are the effects of saturation and carbon lengths on melting points of fatty acids

SOME SHORTHAND NAMING:• Short-hand methods for naming FA

begin with either the carboxylic acid end or the methyl end of the molecule:

lauric acid = 12:0; oleic acid = 18:1

linolenic acid = 18:3 D9,12,15 (This is

also an w-3 fatty acid) 18:3 indicates an 18C fatty acid with three double bonds; D9,12,15 shows the positions of the double bonds; and w-3 states the double bond begins at C3 from the methyl group (opposite of the carboxyl group)

This is an example of an omega-3 fatty acid.

Commercial hydrogenation converts FAs in thecis configuration (shown on the left) into saturatedFA. However, side reactions also produce trans FA (shown on the right). Trans FA increase LDL*lipids in the body that cause a buildup of arteriallipid deposits leading to atherosclerosis. *low density lipoprotein (containing so called “bad” cholesterol)

SATURATED VS. UNSATURATED FA• There is a wide variety of FA consumed in our diets and

it depends on the source of the lipids.

There are two issues, then, concerningthe consumption of FA in the diet:

1. excessive intake of saturated FA (beef and butter as examples)

2. excessive intake of trans-FA (margarine made by hydrogenation)

Some oils that tend to be low in saturated andtrans-FA are canola, olive and flax seed.

Analysis of Fatty Acids:

Treat (b) and(c) With NaOHand methanolto producefatty acyl methyl esters(transesterification).Process at (e) or (f).

STORED FAT: TRIACYLGLYCEROLS(TGs)

TAG FACTS

• Most of the FAs in TAGs are of mixed chain length and degree of saturation (important for membrane properties).

• The energy obtained by metabolic oxidation of TAGs is ~2.2x that of proteins and carbohydrates.

• TAGs are an important temperature insulator for animals.

SAPONIFICATION(FAT HYDROLYSIS)

Cells produce theirown form of TG hydrol-ysis by using lipase enzymes to separateFAs prior to transportingthem and combining them into new lipids.

STRUCTURAL FORMS OF LIPIDS

• There are three types of lipids that are used to form tissue structures (membranes):

• GLYCEROPHOSPHOLIPIDS• SPHINGOLIPIDS• STEROIDS (CHOLESTEROL)

GLYCEROPHOSPHOLIPIDSGlycerophospholipids (phospholipids) are a

variation of TGs, but they substitute a polar

headgroup for one of the FA parts. Shown below is phosphatidic acid:

TYPES AND NATURE OF HEAD GROUPS:

Example – phosphatidyl choline

The choline group, shown in the box, is one type of phospholipid head group that has a positive chargelocated on the N. This groups interacts with wateron either side of a membrane.

OTHER POLAR HEAD GROUPS:

GLYCEROPHOSPHOLIPIDS ARE GLYCEROL*UNITS TO WHICH ARE ESTERIFIED:

2 FATTY ACIDS AND ONE POLAR HEAD UNIT

THE FATTY ACIDS ARE COMMONLY MIXED –ONE SATURATED AND ONE UNSATURATED

THE HEAD UNITS CONSIST OF SIX COMMONTYPES – CHOLINE AND ETHANOLAMINE ARETWO OF THE MOST COMMON TYPES.

*GLYCEROL IS A “HINGE MOLECULE”

GLYCEROPHOSPHOLIPIDS (PL) FOR MOST OF US SERVE AS MEMBRANECOMPONENTS PRIMARILY AND ASFUEL SECONDARILY.

THE POLAR BEAR USES PL AS:

1) AN INSULATOR2) A FUEL3) A SOURCE OF WATER:

PL PHG + FA FA (- 2C) HOH

SPHINGOLIPIDS

THE RIDDLE OF THE SPHINX:

What goes on four feet in the morning;Two feet in the afternoon; andThree feet in the evening?

sjiggw

A CLASS OF LIPIDS WHOSESTRUCTURE PERPLEXEDINVESTIGATORS WERE KNOWN AS SPHINGOLIPIDS

SPHINGOLIPIDS USE SPHINGOSINE AS THEIRHINGE MOLECULE INSTEAD OF GLYCEROL.

Examples of some sphingolipids:

WHERE AND WHY ARE SPHINGOLIPIDS PRESENT?

1. ARE OFTEN FOUND IN NERVOUS MEMBRANES OF HIGHER ANIMALS.

2. SPHINGOMYELIN IS ALSO FOUND IN MUSCLE MEMBRANES.

3. GLYCOSPHINGOLIPDS ARE ALSO IMMUNOMARKERS FOR CELLS.

A NOTE TO CONSIDER:

THE DEGRADATION OF GANGLIOSIDES OCCURSIN LYSOSOMES AND IS AN IMPORTANT PROCESS.IF A DEFICIENCY IN ONE OR MORE DEGRADATIVEENZYMES OCCURS THERE, THEN A DISEASE KNOWN AS A METABOLIC STORAGE DISEASE MAY OCCUR.

AN EXAMPLE IS TAY-SACH’S DISEASE IN WHICH A GANGLIOSIDE (GM2) IS ONLY PARTIALLY DEGRADEDDUE TO THE DEFICIENCY OF THE ENZYME: HEXOS-AMINIDASE A. THE EXCESS LIPID CAUSES MENTALRETARDATION AND EVENTUALLY DEATH.

ISOPRENE & CHOLESTEROL

• A final consideration with lipids and membranes is with the steroid known as cholesterol (no fatty acid components here).

• Cholesterol is synthesized from terpene units known as isoprene:

ISOPRENE IS A DANGEROUSLIPID:

1. IT IS A COLORLESS LIQUID2. HIGHLY INFLAMMABLE3. OBTAINED FROM REFINING OIL4. STARTING MATERIAL FOR MAKING SYNTHETIC RUBBER

BUT, IN THE BODY – IT IS MADE FROM acetyl CoA

SOME COMMONLY KNOWN TERPENES:

CHOLESTEROL

1. is a steroid - a terpenoid lipid with four

fused rings.

2. is the starting molecule for hormone

synthesis.

3. An important component of plasma

membranes, some intracellular

organelles, and blood lipoprotein

complexes.

1

2

3

1. The hydroxyl group on cholesterol is often esterified to fatty acids to make cholesteryl esters.

2. The methyl groups on cholesterol can be substituted with other groups (e. g., fluorine) and profoundly change the properties of the molecule.

3. The tail of the cholesterol molecule is often shortened and substituted to form hormones.

SUMMARY

• FATTY ACIDS ARE THE BUILDING BLOCKS OF MOST BIOLOGICAL LIPIDS.

• FATS ARE STORED AS TRIACYLGLYERIDES.• LIPIDS ARE INCORPORATED INTO

MEMBRANES AS PHOSPHOLIPIDS, SPHINGOMYELINS AND CHOLESTEROL.

• THE PROPERTIES OF EACH OF THESE CLASSES OF LIPIDS DETERMINES THEIR BIOLOGICAL USE.

IMPORTANT THINGS TO STUDY FROM THIS LECTURE:

1. WHAT IS THE DIFFERENCE BETWEEN FAT AND LIPIDS?2. WHAT ARE THE BIOLOGICAL USES OF LIPIDS?3. ARE LIPIDS NON-POLAR? WHAT DOES THAT MEAN?4. WHAT GENERAL STRUCTURAL PROPERTIES DO FATTY ACIDS HAVE?5. HOW ARE THEY NAMED?6. WHAT PROPERTIES DO SATURATION/UNSATURATION GIVE TO FATTY ACIDS? WHAT ARE TRANS FATTY ACIDS?7. IN REFERENCE TO 6. – WHAT KINDS OF FATTY ACIDS ARE IMPORTANT IN THE DIET?8. HOW CAN FATTY ACIDS BE ANALYZED?9. WHAT IS SAPONIFICATION? HOW ARE FATS METABOLIZED IN TISSUES FOR EXAMPLE – TO PRODUCE STORAGE FORMS IN CELLS?10. CAN YOU DISTINGUISH BETWEEN GLYCEROPHOSPHOLIPID AND SPHINGOLIPID STRUCTURES? WHERE DO THESE LIPIDS OCCUR?11. CAN YOU GIVE SOME BASIC STRUCTURAL PROPERTIES OF CHOLESTEROL AND WHERE IT IS LOCATED IN THE BODY?