Dr Vivek Joshi

Contents and Learning Objectives Definition of lipids Classification of lipids by function Classification of lipids by structure Fatty Acids- structure, EFA, PUFA Triglyceride- structure, properties

Rancidity of fats Waxes

Complex Lipids- Phospholipids & Glycolipids Clinical Aspect- Myelin Sheath and Multiple Sclerosis Clinical Aspect- Lipid Storage Diseases

Membrane structure & transport Steroids

Cholesterol and Lipoproteins: Clinical importance Hormones & their biological functions

Prostaglandins, Leukotrienes, and Thromboxanes

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Lipids in General

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Defined in terms of solubility, and not in terms of particular structures (unlike carbohydrates, proteins and nucleic acids)

• Heterogeneous• Organic• Insoluble in water• Soluble in non polar solvents

Wax

Oils

Lipids DefinitionA heterogeneous family of organic compounds

classified together on the basis of common solubility properties: insoluble in watersoluble in organic solvents like diethyl ether,

acetone and dichloromethane

Lipid family includes: fatty acids, triglycerides, phospholipids, and glycolipids. cholesterol, steroid hormones, and bile acids lipid-soluble vitamins.prostaglandins, leukotrienes, and thromboxanes.

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Lipid ClassificationA. By function:

Storage of energyMembrane componentsMessengers

B. By structure:Simple LipidsComplex LipidsSteroidsDerived Lipids

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Classification by FunctionStorage of energy: Efficient source of energy Lipids: 9 kcal/gram, much more than Carbohydrates: 4 kcal/gram Example: Triglycerides

Membrane components Lipids are ‘water insoluble’ and hydrophobic They provide membranes, that separate aqueous compartments Example: Complex lipids and Cholesterol

Messengers They are ‘Chemical messengers’

Primary messengers: delivers signal from one part of body to another. e.g. steroid hormones

Secondary messengers: mediate local hormonal response. E.g. prostaglandins

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Classification by StructureSimple Lipids:

Esters of fatty acids with glycerolTriglyceride = 3 Fatty acids + Glycerol

Complex Lipids:Simple lipids + Additional non lipid groups

Phospholipids Glycolipids

Steroids:CholesterolSteroid hormones

Derived Lipids:Prostaglandins, Leukotrienes, and Thromboxanes

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SIMPLE LIPIDS

8Simple Lipids

Fatty acids

9Simple Lipids

Fatty acids (contd.)

10Simple Lipids

Fatty acids (contd.)

Essential fatty acids:Humans can synthesize saturated and mono-unsaturated

FAHumans can not synthesize Linoleic (18:2) and

Linolenic (18:3) acidsMust be obtained from the diet (plants)

PUFA: Fatty acids having more than 1 double bonds (Poly

Unsaturated Fatty Acids)Example: both essential fatty acids

11Simple Lipids

TriglycerideAlso named as ‘Triacylglycerol’

Here, acyl= fatty acidEsters of glycerol with three fatty acids.

Most abundant family of lipids in plant and animal cells. Major components of the human diet

12Simple Lipids

Triglyceride (contd.)

Fatty acids in structure of triglyceride:Mostly unbranched fatty acidsTheir size ranges from about 10 to 20 carbonsThey contain even number of carbons (10, 12, 14 etc.)Apart from the –COOH group, they have no functional

groups, except that some do have double bond (i.e. unsaturated FA)

In most unsaturated fatty acids, cis isomers predominates

13Simple Lipids

Properties of TriglyceridesA. Physical state: depends on fatty acid components

Melting point of triglyceride increases as the number of carbons in the hydrocarbon chains increases and as the number of double bonds decreases.

Longer the chain, MP ↑ More double bonds, MP ↓

FATS: A mixture of triglycerides rich in long chain, saturated fatty acids

Semisolid or solid at room temperature. Animal fats

OILS: A mixture of triglycerides rich in long chain, unsaturated fatty acids

Liquid at room temperature Vegetable oilsVegetable oils

Pure fats and oils are colorless, odorless and tasteless

14Simple Lipids

Properties of Triglycerides (contd.)

The lower melting points of triglycerides rich in unsaturated fatty acids are related to differences in their three-dimensional shape. Chains of saturated fatty

acids can lie parallel with strong forces between their chains; they pack into well-ordered, compact forms

Because of the double bonds in unsaturated fatty acids, their chains have a less ordered structure and forces between them are weaker

15Simple Lipids

Properties of Triglycerides (contd.)

B. Hydrogenation:Simply, Hardening of lipids“Reduction of some or all of the carbon-carbon

double bonds of an unsaturated triglyceride using H2 and a catalyst”.

In practice, the degree of hardening is carefully controlled to produce fats of a desired consistency. Fats for kitchen use (Crisco, Spry, Dexo etc.) Margarine and other butter substitutes

16Simple Lipids

Rancidity of Lipids“Chemical decomposition of lipids due to oxidation or

hydrolysis, leading to foul taste and odors”

The double bonds in fats and oils are subject to oxidation by air, producing compounds with foul taste and odors

Another cause of unpleasant taste is hydrolysis of triglyceride, which may produce short chain FA, such as butyric acid, which have unpleasant odors

Prevention:Refrigeration (low temperature)Dark containers (protection from UV lights)Addition of antioxidants (prevents oxidation)

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Simple Lipids

COMPLEX LIPIDS

18Complex Lipids

Complex LipidsOverview of simple and complex lipids.

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• Lecithin • Phosphatidylinositol

•Ceramide•Sphingomyelin

Storage lipids Membrane lipids

•Cerebroside•Ganglioside

Complex Lipids

They are main components of membranesPhospholipids:

contain an alcohol, fatty acids, and a phosphate ester.In glycerophospholipids, the alcohol is glycerol.In sphingolipids, the alcohol is sphingosine.

Glycolipids:alcohol is sphingosine and contain a carbohydrate.

20Complex Lipids

Glycerophospholipids (GPL)Also called as phosphoglycerides.

Second most abundant group of naturally occurring lipids.

Found almost exclusively in membranes, which typically consist of 40% - 50% GPL and 50% - 60% proteins.

21Complex Lipids

Structure of Glycerophospholipids

Similar to triglycerideThe most abundant GPLs are derived from ‘phosphatidic acid’Phosphatidic acid: a molecule in which glycerol is esterified

with two molecules of fatty acid and one of phosphoric acid. Alcohols part is Glycerol C1- usually SFA C2- Always UFA C3- Phosphate group

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

22Phosphatidic acid

Complex Lipids

Various Glycerophospholipids

23Complex Lipids

Importance of Glycerophospholipids

24Complex Lipids

SphingolipidsThe alcohol part is sphingosine (not glycerol)

Ceramide = sphingosine + FAComponent of Cerebrosides, in nervous tissue

Sphingomyelin = Ceramide + PhosphocholineComponent of Myelin, coating of nerve axons

25Complex Lipids

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The Myelin Sheath & Multiple sclerosis

Multiple sclerosis (MS) commonly attacks people in their 20s or 30s and progresses at intervals and at varying rates.

It involves patchy loss of myelin with hardening (sclerosis) of tissue in the CNS.

The symptoms include vision problems, tingling or numbness in the arms and legs, urinary incontinence, tremor (shaking), and stiff gait.

MS is thought to be an autoimmune disorder, but the exact cause is not known.

From Medical Terminology Chapter 17. Nervous System Slides No. 66 & 67Complex Lipids

GlycolipidsThe alcohol part is sphingosine (not glycerol)Glycolipids = Ceramide + CarbohydratesThe carbohydrate is either glucose or galactose.

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Cerebroside = Ceramide + Mono/oligosaccharide

important components nervous tissue

Accounts for 7% of brain's dry weight

Ganglioside = Ceramide + Complex oligosaccharide

cellular recognition and communication

Complex Lipids

Lipid Storage Diseases Complex lipids are constantly being synthesized and decomposed in the body In some genetic diseases, enzymes needed to decompose the complex lipids

are defective or missing. Hence, lipids accumulate and cause an enlarged liver and spleen, mental

retardation, blindness, and may early death No definitive treatment but, can be prevented by antenatal genetic counseling

Disease Name Accumulating Lipid Missing or defective enzyme type

Gaucher’s disease Glucocerebroside β- Glucosidase

Krabbe’s Leukodystrophy

Galactocerebroside β- Galactosidase

Fabry’s disease Ceramide trihexoside α- Galactosidase

Tay-Sachs disease Ganglioside (Ceramide oligosaccharide)

Hexosaminidase A

Niemann-Pick disease Sphingomyelin Sphingomyelinase

28Complex Lipids

STEROIDS

29Steroids

SteroidsCompounds having this tetracyclic ring structure.

Three cyclohexane rings (A, B and C) are connected in the same way as in Phenanthrene

A fused cyclopentane ring (D) is also presentSteroid family includes:

CholesterolSteroid hormonesBile salts

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A B

C D

Steroids

Cholesterol Cholesterol is the most abundant steroid in the human body Main Functions:

Structural component in cell membranes Synthesis of Steroid hormones (corticosteroid and sex

hormones); Bile salts; Vitamin D

It may exist in Free form (cholesterol) Esterified with fatty acids (cholesteryl ester)

It constantly circulates in blood High serum level is a associated with atherosclerosis Cholesterols being hydrophobic, they need a water-soluble

carriers to circulate in aqueous blood → these carriers are LIPOPROTEINS

31Steroids

Steroid Hormones Cholesterol is the starting material steroid hormone synthesis In this process, the side chain on the D ring is shortened by the

removal of a six-carbon unit, and the alcohol group on carbon 3 is oxidized to a ketone.

The resulting molecule, progesterone, serves as the starting compound for both sex and adrenocorticoid hormones

32Steroids

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Steroid Hormones (contd.)

Adrenocorticoid Hormones: Secreted from adrenal cortex Aldosterone:

One of minerolocorticoids Enhances the retention of Na+ and Cl- ions and

elimination of K+ ions in kidneys Cortisol:

Major glucocorticoids Controls carbohydrates metabolism Increases glucose and glycogen synthesis in liver Also antiinflammatory properties

Cortisone: Remarkable antiinflammatory properties

Steroids

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Steroid Hormones (contd.)

Sex Hormones: Testosterone:

Male sex hormone, synthesized in testis Promotes normal growth of male genital organs Development of male secondary sex characteristics Anabolic steroids (that mimic effects of testosterone) are

abused by athletes, as they provide strength and muscle mass

Estradiol: Female sex hormone Development of female secondary sex characteristics Estradiol and progesterone, regulates the cyclic changes

occurring in uterus and ovaries known as menstrual cycle Progesterone:

Prepares uterus for implantation to fertilized ovum, inhibits further ovulation during pregnancy

Synthetic progesterone like compounds (Norethindone, Mifepristone {RU 486}) are used in Oral Contraceptives

Steroids

Bile Salts They are the oxidation products of cholesterol.

Glycocholate: containing Glycine (a amino acid) Taurocholate: containing Taurine (a cysteine derivative)

Synthesized in the liver, stored in the gallbladder, and secreted into the intestine

They are powerful detergents and can emulsify dietary fats and aid in their absorption and digestion

Emulsification: Dispersion and increasing the surface area of lipids

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HO

H3C

CH3

H3C

OH

HO NH

O

HO

H3C

CH3

H3C

OH

HO NH

O

SO32-

Glycocholate(from glycine)

Taurocholate(from taurine)

COO-

Steroids

Vitamin DSynthesized in skin from cholesterolCalcitriol (1,25 dihydroxy Cholecalciferol)Functions in calcium metabolismDeficiency:

Rickets in children, Osteomalacia in adults

36Steroids

DERIVED LIPIDS

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Prostaglandins (PG)ProstaglandinsProstaglandins:: a family of compounds that have the 20-

carbon skeleton of prostanoic acid.

Prostaglandins are not stored in tissues as such, but are synthesized from membrane-bound arachidonic acids in response to specific physiological triggers.

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COOH2

3

4

5

67

89

2011

1213

1415

1617

1819

1

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Derived Lipids

Prostaglandins

COX-1: production of PG in normal physiological conditions COX-2: production of PG in inflammation

Biological importance of PG:Cause constriction or dilation of smooth muscles Cause aggregation or disaggregation of plateletsSensitize spinal neurons to pain Regulate inflammatory reactions Control hormone regulation

39Derived Lipids

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9 9

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Arachidonic acid

PGF2PGE2

PGG2

Aspirin and other NSAIDs inhibit this enzyme

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9

11

9

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OOH

COOHO

O

OH

COOH

O

HO

COOH

OH

COOH

2O2

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cyclooxygenase (COX)

HO

HO

Catalyzing enzyme is Cyclooxygenase [COX]

Thromboxanes 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.

Aspirin is also used long-term, at low doses, to help prevent heart attacks, strokes and blood clot formation in people at high risk for developing blood clots

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O

OOH

COOH

Thromboxane A2

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11 201512

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Derived Lipids

LeukotrienesLeukotrienes are also synthesized from arachidonic

acid.They occur mainly in leukocytes and associated with

immune system.

They produce long lasting muscle contractions, especially in the lungs and thereby can cause asthma-like attacks.

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

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OH OHCOOH

Leukotriene B4

1512

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Derived Lipids

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