MEDC 527 Fall 2008 1

Lipids

Function of Lipids

Energy storage molecules in animals [release 9 kcal/g versus 4

kcal/g by carbohydrates] Form membranes (cellular or sub-cellular) that separate

compartments in cells [lipids are insoluble in water so help

generate membranes] Serve as chemical messengers [steroid hormones are primary

messengers, while prostaglandins and thromboxanes are secondary

messengers mediating hormonal response]

MEDC 527 Fall 2008 2

Classification of Lipids by Structure Lipids can be classified into four groups based on their structure

Lipids

Simple and Complex Lipids

Simple Complex

Phospholipids Glycolipids

Glycerophospholipids Sphingolipids

Fatty acid

Fatty acid

Fatty acidGly

cero

l Fatty acid

Fatty acid

AlcoholGly

cero

l

PO4

Fatty acid

choline

Sp

hin

gosin

e

PO4

Glup / Galp

Fatty acid

Sp

hin

gosin

e

1) Simple lipids, e.g., fats; 2) Complex lipids

3) Steroids; 4) Prostaglandins, thromboxanes, and leukotrienes

MEDC 527 Fall 2008 3

Triglycerides Animal fats and vegetable oils are triglycerides Triesters of glycerol and long chain carboxylic acids called fatty acids Glycerol component cannot vary, but the fatty acid component may vary Fatty acids are unbranched carboxylic acids having 10 to 20 carbons in even

number Some fatty acids have double bond(s). Typically these double bond(s) are cis

Lipids

CHOH

CH2OH

CH2OH

Glycerol

+

CH

CH2

CH2

O (CH2)14CH3

O

O(CH2)16CH3

O

OCH3(CH2)7CH=CH(CH2)7

O

OH

O

OH

O

A triglyceride

palmitate (16:0)

stearate (18:0)

oleate (18:1)

n

m

p

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Generally fats from animals are solids at room temperature. Most fats from

plants and fish are liquids. Liquid fats are referred to as oils. Presence or absence of unsaturation makes a triglyceride solid or liquid

Properties of Triglycerides

HOOCHOOCHOOCHOOCHOOCHOOC

HOOCHOOC

HOOCHOOC

HOOC

HOOC

HOOCHOOCHOOCHOOCHOOCHOOC

Saturated and trans fatty acids stack well Unsaturated cis fatty acids do not ….(greater hydrophobic interactions; (lesser hydrophobic interactions; greater order in arrangement; lesser order in arrangement; carries over to triglyceride structure) carries over to triglyceride structure)

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Saturated Fatty Acids Tm (OC)

12:0 CH3(CH2)10COOH lauric acid 44

14:0 CH3(CH2)12COOH myristic acid 58

16:0 CH3(CH2)14COOH palmitic acid 63

18:0 CH3(CH2)16COOH stearic acid 70

20:0 CH3(CH2)18COOH arachidic acid 77

Unsaturated cis Fatty Acids

16:1 CH3(CH2)5 CH=CH(CH2)7COOH palmitoleic acid 1

18:1 CH3(CH2)7 CH=CH(CH2)7COOH oleic acid 16

18:2 CH3(CH2)4 (CH=CHCH2)2(CH2)6COOH linoleic acid -5

18:3 CH3CH2(CH=CHCH2)3(CH2)6COOH linolenic acid -11

20:4 CH3(CH2)4 (CH=CHCH2)4(CH2)2COOH arachidonic acid -49

Properties of Triglycerides

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Pure fats and oils are colorless, odorless and tasteless. Fats are not soluble in water. They are hydrophobic molecules and soluble in organic

solvents The presence of double bonds, especially in plant fats, makes them susceptible to

oxidation. Heavily oxidized fats are not edible. These generate rancidity. The ester group in fats is susceptible to hydrolysis releasing acidic groups, e.g.,

butyric acid, which have bad taste and odor.

Properties of Triglycerides

CH

CH2

CH2

O R

O

OR'

O

OR"

O

CH

CH2

CH2

OH

OH

OH

O NaO

R

O NaO

R'

O NaO

R"

NaOH _ + _ + _ ++

SaponificationMixture of fatty acid sodium salt

(Soap)

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Complex lipids constitute the main component of membranes. Two main types of complex lipids – phospholipids and glycolipids.

Phospholipids contain a phosphate group, while glycolipids contain a

carbohydrate group Phospholipids can be made from glycerol or from sphingosine

Complex Lipids

Phosphatidylcholine (lecithin)(A glycerophospholipid)

CH

CH2

CH2

O

O

O

P

(CH2)16CH3

O

O

(CH2)7CH=CHCH2CH=CH(CH2)4CH3

O

O

O

CH2CH2N(CH3)+

_

choline

A sphingomyelin (A sphingolipid)

OP

O

O

ONH

OH

O

CH3

CH3

Me3N +_

sphingosine

choline

+

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Membranes

Complex lipids containing unsaturated fatty acids constitute cell membranes. Membranes are made up of lipid bi-layers.

The Fluid Mosaic Model of Cell Membranes

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Steroids

Steroids constitute the third major class of lipids Steroids are cyclopentanoperhydrophenanthrenes. Cholesterol is the commonest steroid. It is present cell membranes. It is also

present in lipoprotein particles, e.g., LDL, HDL, and others

A B

C DCyclopentanoperhydrophenanthrene

(Steroid skeleton)

CH3

CH3

CH3

CH3

CH3

OH

Cholesterol

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Lipoprotein Particles Lipoprotein particles transport cholesterol in blood Contain a core of hydrophobic lipid molecules surrounded by a shell of hydrophilic

molecules such as proteins and phospholipids At least four kinds of particles: HDL, LDL, VLDL and Chylomicrons

A Model of a Lipoprotein Particle

Cholesterol

Cholesterol ester

Phospholipids

Apolipoprotein

SmallHighCE > TGHDL

CE >> TGLDL

TG > CEVLDL

LargeLowTG >> C, CEChylomicrons

SizeDensityComposition

SmallHighCE > TGHDL

CE >> TGLDL

TG > CEVLDL

LargeLowTG >> C, CEChylomicrons

SizeDensityComposition

MEDC 527 Fall 2008 11

Prostaglandins, Thromboxanes and Leukotrienes

Prostaglandins are derived from arachidonic acid They have a wide variety of effects of the body; they can lower or raise blood

pressure, cause inflammation, induce blood clotting and induce labor Aspirin and other NSAIDs inhibit the enzyme (cyclooxygenase COX) involved in

the synthesis of prostaglandins

HOOC

OH

O

OH

HOOC

OH

OH

OH

HOOC

O

OHOOC

OH

HOOC

OH OH

Arachidonic Acid

PGE2 PGF2

Thromboxane A2 Leukotriene B4