paper : 05 metabolism of lipids module: 01 prologue to lipids

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Biochemistry METABOLISM OF LIPIDS

Prologue to Lipids

Dr. Vijaya Khader

Dr. MC Varadaraj

Paper : 05 Metabolism of Lipids

Module: 01 Prologue to Lipids

Principal Investigator

Paper Coordinator and

Content Writer

Dr. Sunil Kumar Khare, Professor,

Department of Chemistry, IIT-Delhi

Dr. Suaib Luqman, Scientist (CSIR-CIMAP)

& Assistant Professor (AcSIR)

CSIR-CIMAP, Lucknow

Content Reviewer Prof. Prashant Mishra, Professor,

Department of Biochemical Engineering

and Biotechnology, IIT-Delhi

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Prologue to Lipids

DESCRIPTION OF MODULE

Subject Name Biochemistry

Paper Name 05 Metabolism of Lipids

Module Name/Title 01 Prologue to Lipids

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Prologue to Lipids

1. Objectives

To understand what is lipid

Why they are important

How they occur in nature

2. Concept Map

3. Description

3.1 Prologue to Lipids

In 1943, the term lipid was first used by BLOOR, a German biochemist.

Lipids are heterogeneous group of compounds present in plants and animal tissues related either actually or

potentially to the fatty acids. They are amphipathic molecules, hydrophobic in nature originated utterly or in part

by thioesters (carbanion-based condensations of fatty acids and/or polyketides etc) or by isoprene units

(carbocation-based condensations of prenols, sterols, etc). Lipids have the universal property of being:

i. Quite insoluble in water (polar solvent)

ii. Soluble in benzene, chloroform, ether (non-polar solvent)

LIPIDS

Fatty Acids Glycerol

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Prologue to Lipids

Thus, lipids include oils, fats, waxes, steroids, vitamins (A, D, E and K) and related compounds, such as

phospholipids, triglycerides, diglycerides, monoglycerides and others, which are allied more by their physical

properties than by their chemical assests.

They are vital constituents related to diet because of high energy value, essential fatty acids and fat soluble

vitamins present in the content of fat foods. Lipids serve as adept source of energy when stored in adipose tissue.

Fat also dole out as Thermal Insulators in the subcutaneous tissues and in the region of some organs and non-

polar lipids acts as Electrical Insulators permitting quick propagation of depolarization waves by the side of

myelinated nerves. Lipoproteins (combinations of lipid and protein) transport lipids in the blood and the

biochemical acquaintance of lipids is obligatory in understanding atherosclerosis, diabetes mellitus, obesity etc.

The function of diverse polyunsaturated fatty acids (PUFAs) in nutrition and health can also be best understood

by studying its biochemical profile.

Chemically, lipids are defined as esters of glycerol and fatty acids or else refer as the triglycerides of fatty acids.

They are the substances of natural origin, soluble in non-polar solvents and hence may be extorted by using

organic solvents such as methanol. Lipids could be fractionated by either using adsorption chromatography (thin

layer chromatography) or reverse-phase chromatography.

Fatty acid

It may be defined as an organic acid that occurs in a natural triglyceride and is a mono carboxylic acid ranging

in chain length from C4-C24 carbon atoms. Fatty acids are obtained from the hydrolysis of fats. They are

naturally occurring straight chain derivatives containing carbon atoms with even numbers (4-28) as they

assemble from two carbon units. Typically derived from triglycerides or phospholipids, fatty acids are vital

sources of fuel yielding huge quantities of ATP. Fatty acids that contain C=C are recognized as unsaturated fatty

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Prologue to Lipids

acid (UFAs) and those lacking double bonds are recognized as saturated fatty acid (SFAs). They are named after

corresponding hydrocarbons and vary in length. UFAs end with suffix-enoic and SFAs ends with suffix-anoic.

Based on length as short to very long, they may be categorized as under:

SCFA: Short Chain Fatty Acids with less than six carbons (e.g. butyric acid).

MCFA: Medium Chain Fatty Acids with 6-12 carbons.

LCFA: Long Chain Fatty Acids with 13-21 carbons.

VLCFA: Very Long Chain Fatty Acids with more than 22 carbons.

The condensation of Acetyl Co-A, a coenzyme, results in the biosynthesis of fatty acids as it carries two carbon

units. That is why all FAs have even numbers of carbon atoms.

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Prologue to Lipids

Unsaturated Fatty Acid (UFA)

UFAs contain carbon units linked by double bonds, saturated with hydrogen atoms that convert double bonds to

single bonds (one or more double bonds between carbon units). The carbon atoms occur either in a cis or a trans

configuration. When two hydrogen atoms nearby to the double bond fasten on the chain (same side), it is cis

configuration of fatty acid (Oleic acid, Linoleic acid etc). When the neighboring two hydrogen atoms lie on the

chain (opposite side), it is trans configuration of fatty acid (Elaidic acid, Vaccenic acid etc). Unsaturated fatty

acid may be of following types.

Monounsaturated: Presence of one double bond

Polyunsaturated: Presence of two or more double bond

Eicosanoid: are signaling molecules made by the oxidation of 20-carbon fatty acids

Prostanoid: It includes (a) Prostaglandins e.g. PGE1, (b) Prostacyclin e.g. PCI2, (c) Thromboxanes e.g.

TXA2

Leukotriene: Containing three double bonds sequentially e.g. LTB4, LTE4

Table 1. Selected examples of Unsaturated Fatty Acids

n-x Name Structure & Chemical Formula C:D Δ

x

n-3 α-Linolenic acid CH3CH2CH=CHCH2CH=CHCH2CH=CH(CH2)7COOH

18:3 cis,cis,cis-

Δ9,Δ

12,Δ

15

Eicosapentaenoic

acid

CH3CH2CH=CHCH2CH=CHCH2CH=CHCH2CH=CHCH2CH=CH(CH2)3

COOH

20:5 cis,cis,cis,ci

s,cis-Δ5, Δ

8,

Δ11

, Δ14

, Δ17

Docosahexaenoi

c acid

CH3CH2CH=CHCH2CH=CHCH2CH=CHCH2CH=CHCH2CH=CHCH2C

H=CH(CH2)2COOH

22:6 cis,cis,cis,ci

s,cis,cis-Δ4,

Δ7, Δ

10, Δ

13,

Δ16

, Δ19

n-5 Myristoleic acid CH3(CH2)3CH=CH(CH2)7COOH 14:1 cis-Δ9

n-6 Linoleic acid CH3(CH2)4CH=CHCH2CH=CH(CH2)7COOH

18:2 cis,cis-Δ9,

Δ12

Linoelaidic acid CH3(CH2)4CH=CHCH2CH=CH(CH2)7COOH 18:2 trans,trans-

Δ9, Δ

12

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Prologue to Lipids

Arachidonic acid CH3(CH2)4CH=CHCH2CH=CHCH2CH=CHCH2CH=CH(CH2)3COOH

20:4 cis,cis,cis,ci

s-Δ5Δ

8, Δ

11,

Δ14

n-7 Palmitoleic acid CH3(CH2)5CH=CH(CH2)7COOH 16:1 cis-Δ9

Vaccenic acid CH3(CH2)5CH=CH(CH2)9COOH 18:1 trans-Δ11

n-9 Oleic acid CH3(CH2)7CH=CH(CH2)7COOH 18:1 cis-Δ9

Elaidic acid CH3(CH2)7CH=CH(CH2)7COOH 18:1 trans-Δ9

Erucic acid CH3(CH2)7CH=CH(CH2)11COOH 22:1 cis-Δ13

n-10 Sapienic acid CH3(CH2)8CH=CH(CH2)4COOH 16:1 cis-Δ6

C:D = Number of carbon units and double bond ratio

Adapted and Modified from http://en.wikipedia.org/wiki/Fatty_acid

Table 2. List of Other Unstaurated Fatty Acids

C:D

ω-n Name Structure & Chemical Formula Δn Configuration Source

16:1 ω-7

Palmitoleic

acid

CH3(CH2)5CH=CH(CH2)7COOH Δ9 cis Macadamia nut

18:1 ω-7

Vaccenic

acid

CH3(CH2)5CH=CH(CH2)9COOH Δ11

trans

Butter, Milk,

and Yogurt

ω-9 Oleic acid CH3(CH2)7CH=CH(CH2)7COOH Δ

9 cis

Canola, Olive

and Pecan oil

ω-9 Elaidic acid CH3(CH2)7CH=CH(CH2)7COOH Δ

9 trans

Vegetable oil

(hydrogenated)

18:2

ω-6 Linoleic acid CH3(CH2)4CH=CHCH2CH=CH(CH2)7COOH

Δ9,12

cis

Chicken fat,

Olive and

Peanut oil

18:3

ω-3 α-Linolenic

acid

CH3CH2CH=CHCH2CH=CHCH2CH=CH(CH

2)7COOH

Δ9,12,1

5 cis

Chiaseeds,

Flaxseeds and

Walnuts

ω-6 γ-Linolenic

acid

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

CH2)4COOH

Δ6,9,12

cis

Black currant

oil, Borage oil,

Evening

primrose oil and

safflower oil

18:4

ω-3 Stearidonic

acid

CH3CH2CH=CHCH2CH=CHCH2CH=CHCH2

CH=CH(CH2)4COOH

Δ6,9,12,

15

cis

Blackcurrant,

Corn gromwell

and Seed oils of

hemp

20:1 ω-7

Paullinic

acid CH3(CH2)5CH=CH(CH2)11COOH

Δ13

cis Guarana

ω-9 Gondoic


Δ11

cis

Jojoba oil (non-

caloric and non-

digestible but

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Prologue to Lipids

edible)

20:3

ω-6

Dihomo-γ-

linolenic

acid

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

CH2)6COOH

Δ8,11,1

4 cis

Trace amounts

(Animal

products)

ω-9 Mead acid CH3(CH2)7CH=CHCH2CH=CHCH2CH=CH(

CH2)3COOH

Δ5,8,11

cis Cartilage

20:4 ω-6

Arachidonic

acid

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

H2CH=CH(CH2)3COOH

Δ5,8,11,

14

cis Dairy, Eggs,

Meat

20:5

ω-3 Eicosapenta

enoic acid


CH=CHCH2CH=CH(CH2)3COOH

Δ5,8,11,

14,17

cis

Cod liver,

Herring,

Menhaden,

Mackerel,

Salmon and

Sardine

22:1 ω-9 Erucic acid CH3(CH2)7CH=CH(CH2)11COOH

Δ13

cis

Mustard oil,

Wallflower seed

22:4 ω-6

Docosatetrae

noic acid

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

H2CH=CH(CH2)5COOH

Δ7,10,1

3,16

cis -

22:6

ω-3 Docosahexa

enoic acid


CH=CHCH2CH=CHCH2CH=CH(CH2)2COO

H

Δ4,7,10,

13,16,19 cis

Fish oil and

Maternal milk

24:1

ω-9 Nervonic


Δ15

cis

Flaxseed, King

Salmon,

Macademia

nuts, Sesame

seed and

Sockeye salmon

Saturated Fatty Acid (SFA)

They are long chain carboxylic acids without double bonds but with 12-24 carbon units. As its name indicates

they are saturated with hydrogen atoms having solitary bonds with each carbon units inside the chain has 2

hydrogen atoms (except 3 hydrogens at the end for omega carbon). Examples of the SFAs are Capric acid,

Palmitic acid, Stearic acid etc.

Table 2. List and Examples of Saturated Fatty Acids

C:D Name Chemical Formula Nomenclature 3:0 Propionic acid CH3CH2COOH Propanoic acid

4:0 Butyric acid CH3(CH2)2COOH Butanoic acid

5:0 Valeric acid CH3(CH2)3COOH Pentanoic acid

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Prologue to Lipids

6:0 Caproic acid CH3(CH2)4COOH Hexanoic acid

7:0 Enanthic acid CH3(CH2)5COOH Heptanoic acid

8:0 Caprylic acid CH3(CH2)6COOH Octanoic acid

9:0 Pelargonic acid CH3(CH2)7COOH Nonanoic acid

10:0 Capric acid CH3(CH2)8COOH Decanoic acid

11:0 Undecylic acid CH3(CH2)9COOH Undecanoic acid

12:0 Lauric acid CH3(CH2)10COOH Dodecanoic acid

13:0 Tridecylic acid CH3(CH2)11COOH Tridecanoic acid

14:0 Myristic acid CH3(CH2)12COOH Tetradecanoic acid

15:0 Pentadecylic acid CH3(CH2)13COOH Pentadecanoic acid

16:0 Palmitic acid CH3(CH2)14COOH Hexadecanoic acid

17:0 Margaric acid CH3(CH2)15COOH Heptadecanoic acid

18:0 Stearic acid CH3(CH2)16COOH Octadecanoic acid

19:0 Nonadecylic acid CH3(CH2)17COOH Nonadecanoic acid

20:0 Arachidic acid CH3(CH2)18COOH Eicosanoic acid

21:0 Heneicosylic acid CH3(CH2)19COOH Heneicosanoic acid

22:0 Behenic acid CH3(CH2)20COOH Docosanoic acid

23:0 Tricosylic acid CH3(CH2)21COOH Tricosanoic acid

24:0 Lignoceric acid CH3(CH2)22COOH Tetracosanoic acid

25:0 Pentacosylic acid CH3(CH2)23COOH Pentacosanoic acid

26:0 Cerotic acid CH3(CH2)24COOH Hexacosanoic acid

27:0 Heptacosylic acid CH3(CH2)25COOH Heptacosanoic acid

28:0 Montanic acid CH3(CH2)26COOH Octacosanoic acid

29:0 Nonacosylic acid CH3(CH2)27COOH Nonacosanoic acid

30:0 Melissic acid CH3(CH2)28COOH Triacontanoic acid

31:0 Henatriacontylic acid CH3(CH2)29COOH Henatriacontanoic acid

32:0 Lacceroic acid CH3(CH2)30COOH Dotriacontanoic acid

33:0 Psyllic acid CH3(CH2)31COOH Tritriacontanoic acid

34:0 Geddic acid CH3(CH2)32COOH Tetratriacontanoic acid

35:0 Ceroplastic acid CH3(CH2)33COOH Pentatriacontanoic acid

36:0 Hexatriacontylic acid CH3(CH2)34COOH Hexatriacontanoic acid

Modified and Adapted from http://en.wikipedia.org/wiki/Fatty_acid

Essential Fatty Acid (EFA)

They are indispensable for the human body not produced in adequate amount from substrates, and consequently

ought to be obtained from diet (food). The idiom ‘EFA’ refers to fatty acids obligatory for biological processes

and excludes those fats that merely act as fuel. Two vital series of EFAs have been reported: (i) Three carbon

units with double bond removed from the methyl end and (ii) Six carbon units with double bond removed from

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Prologue to Lipids

the methyl end. Omega 3-fatty acid (α-linolenic acid = ALA) and Omega 6-fatty acid (Linoleic acid = LA) are

the two EFAs widely distributed in plant oils. Humans lack the ability to synthesize these two EFAs due to

absence of desaturase enzymes required for their production. In 1923, these two EFAs were preferred as Vitamin

F but later (1929), studies on mice revealed that these two EFAs should be categorized under fats rather

vitamins. Omega-3 fatty acid (Docosahexaenoic acid) and Omega 6-fatty acid (γ- Linoleic acid) are occasionally

referred to as ‘Conditionally Essential’ as they happen to indispensable under disease or some developmental

circumstances. In the human body, EFAs dole out numerous functions such as:

Customized to make

o Eicosanoids: Distressing several cellular functions including inflammation

o Endocannabinoids: Upsetting mood, behavior and inflammation

o Lipoxins: A faction of eicosanoid derivatives produced from ω-6 EFAs via the

lipoxygenase pathway and resolvins from ω-3 (down regulating

inflammation in the presence of acetylsalicylic acid)

o Epoxyeicosatrienoic acids (EETs), Hepoxilins, Isofurans, Isoprostanes, Neurofurans and

Neuroprotectin D

EFAs affect cellular signaling by forming lipid rafts.

They either activate or inhibit transcription factors such as NF-κB and act on DNA.

Examples of the food sources with EFAs are canola (rapeseed) oil, chia seeds, fish and shellfish, flaxseed

(linseed), hemp seed, leafy vegetables, pumpkin seeds, soya oil, sunflower seeds and walnuts. Nearly, all the

PUFAs in the human diet are EFAs that play a vital part in the existence and loss of cardiac cells. The deficiency

of EFAs results in depression, dermatitis and osteoporosis.

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Prologue to Lipids

Free Fatty Acid

When fatty acids do not affixed to supplementary molecules, they are acknowledged as ‘Free Fatty Acids’

(FFAs) or ‘Uncombined Fatty Acids’ (UCFAs). The FFAs or UCFAs ensued from the triglyceride breakdown,

insoluble in water, circulated, solubilized and transported through albumin (a plasma protein). However, their

blood echelon is restricted by the accessibility of binding sites of albumin.

Table 3. Composition of dietary fats

Monounsaturated Polyunsaturated Saturated Cholesterol Vitamin E

g per 100 g g per 100 g g per 100 g mg per 100 g mg per 100 g

Vegetable Fats Canola (Rapeseed

Oil) 64.3 24.8

5.3 0 22.21

Coconut oil 6.6 1.7 85.2 0 0.66

Corn oil 24.7 57.8 12.7 0 17.24

Cottonseed oil 21.3 48.1 25.5 0 42.77

Hemp oil 15 75 10 0 12.34

Olive oil 69.7 11.2 14.0 0 5.10

Palm kernel oil 11.4 1.6 81.5 0 3.80

Palm oil 41.6 8.3 45.3 0 33.12

Safflower oil 12.6 72.1 10.2 0 40.68

Soybean oil 23.2 56.5 14.5 0 16.29

Sunflower oil 20.2 63.0 11.9 0 49.00

Wheat germ oil 15.9 60.7 18.8 0 136.65

Animal Fats Butter 19.8 2.6 54.0 230 2.00

Duck fat 49.3 12.9 33.2 100 2.70

Lard 43.8 9.6 40.8 93 0.60

Modified and Adapted from http://en.wikipedia.org/wiki/Fatty_acid#Free_fatty_acids

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Prologue to Lipids

Triglycerides (TG)

Are most abundant form of lipids and constitute about 98% of total dietary lipids. TGs are esters of glycerol with

three fatty acid molecules. Glycerol (Alcohols) contains a hydroxyl (OH) moiety and Fatty acid (Organic acids)

encloses a carboxyl (-COOH) group. Both join together to form esters. During each esterification one molecule

of water is released. In TGs, the OH group of the glycerol connects the COOH group of the fatty acid to form

ester bonds. They may be fats and oils and are also known as Triacylglycerol (TAG) or Triacylglyceride. TGs

contain three moles of fatty acids which may be similar or dissimilar. Similar kind of FAs in all the three

positions are called simple TGs e.g. Tripalmitin, triolein etc. Most of the TGs contains different kinds of fatty

acids in position 1, 2 or 3 and are called mixed TGs e.g. Oleodipalmitin etc. There are a lot of triglycerides

obtainable from the oil source, a number of them are highly unsaturated and a few are unsaturated. Saturated are

those having single bonds between the carbon atoms (C-C) where hydrogen atoms bonds with carbon atoms

while unsaturated compounds bears double bonds between carbon units (C=C), plummeting the integer of places

wherever hydrogen atoms bonds with carbon atoms. Furthermore, at room temperature saturated have an

elevated melting point and are solid while unsaturated have a lower melting point and are liquid.

TGs are the vital constituents of animal fats (saturated) including human skin oils and vegetable oil

(unsaturated). In naturally occurring TGs, the chain lengths of the FAs include even number (16, 18, 20) of

carbon units. However, in bacteria and ruminants fat odd number (15) carbon atoms are present. Majority of

natural fats include an intricate blend of individual TGs and due to this, they deliquesce over a wide array of

temperatures. In TGs form, lipids cannot be engrossed by the duodenum unless broke dowm into fatty acids,

monoglycerides and a few diglycerides. In the intestine, TGs ripped into FFAs and monoacylglycerol following

the secretion of bile and lipases in a process called lipolysis. TGs advances to the intestine through enterocyte

cells and reinstate it from their wreckage, wrap up with proteins and cholesterol to guise chylomicrons. An array

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Prologue to Lipids

of tissues incarcerates the chylomicrons and releases the TGs to be worn as an energy source. TGs can pass

through cell membranes freely via the fatty acid transporter (FAT) only after its split into fatty acid and glycerol

by lipoprotein lipases. TGs being the foremost components of chylomicrons and VLDL (very low density

lipoprotein) perform an imperative role (energy source) in metabolism and transporters of dietary fat (38 kJ/g or

9 kcal/g compared to carbohydrates: 17 kJ/g or 4kcal/g). A high level of TGs in human body has been related to

atherosclerosis, stroke risk and heart disease.

In oil paints and coating, di and triunsaturated fatty acid components present in linseed and related oil are used

which apt to congeal in the presence of oxygen. Using trans-esterification phenomenon, TGs are also ripped into

their components in the biodiesel manufacturing. The ensuing esters of FA be able to be worn as a fuel in diesel

engines. The glycerin is used in the production of pharmaceuticals and food. Lysochromes (Fat soluble dye, Oil

Red O, Sudan Black B, Sudan IV) has been employed for staining fatty acids, triglycerides, lipoproteins, and

other lipids.

Lipids contain hydrocarbons which are the base for the structure and function of living cells. The biological

functions of the lipids are as distinct as their chemistry. Oils and fats are the primary stored arrangement of

energy in numerous organisms. Sterols and phospholipids are key structural essentials of biological membranes.

Other lipids, though present in reasonably small quantities, perform crucial roles as electron carriers, anchors for

proteins (hydrophobic), enzyme cofactors, light absorbing pigments, as intracellular messengers, as chaperones

in protein folding of membranes and as an emulsifying agents in the digestive tract.

Being largely hydrocarbon, lipids yield huge amounts of energy on oxidation and represent exceedingly reduced

forms of carbon. Based on biochemical subunits, lipids may be alienated into the following class: saccharolipids,

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Prologue to Lipids

sphingolipids, sterol lipids, polyketides (consequential of ketoacyl subunits condensation), prenol lipids

(resultant of isoprene subunits condensation), glycerophospholipids, glycerolipids and fatty acids.

The major functions of lipids include energy storage, integral part of cell membrane components and signaling.

Oils and fats are the main source of energy in innumerable organisms. Sterols and phospholipids are key

structural elements of membranes. Other present in comparatively diminutive quantities, perform essential roles

as electron carriers, enzyme cofactors, light absorbing pigments, hormones, as intracellular messenger, as an

anchor for hydrophobic proteins, as chaperones in membrane proteins folding, as an emulsifying agent in the

digestive tract. Lipids have a burly relevance in nanotechnology as well as in food and cosmetic industries.

In a nutshell, lipids:

Acts as a fuel in the body

Yields 9.0 kcal of energy per gram

Exerts an insulating effect in the body

Provide padding and protect the internal organs like kidney

Supply EFAs for normal health, development and growth

Vital for fat soluble vitamins

Fundamental constituent of cell wall, cell membrane and cell organelle like mitochondria

The present prologue introduces lipids and their representative of every type with a prominence on their physical

properties and chemical structure.

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Prologue to Lipids

4. Summary

In this lecture we learnt about:

The Definition of Lipids

Their Solubility

Chemical and Biological nature

paper : 05 metabolism of lipids module: 01 prologue to lipids

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