Lipids

Lipids are distinguished by their high solubility in non polar solvents and low solubility in H2O

● Diverse group of compounds including Fats, Oils, Waxes, some vitamins and hormones and most non-protein components of membranesLipids are amphipathic molecules that can be:

(A) Major components of biological membranes● membranes define the basic unit of life (cell) and subcellular compartments (euKaryotes)● includes cholesterol

(B) Major form of stored energy in biological systems● lipids are largely reduced compounds; complete oxidation of lipids generates lots of energy (ie. more than from sugars)(C) Hormones● signal transduction (communication) between cells

Lipids are non-polar (hydrophobic) compounds, soluble in organic solvents.

Most membrane lipids are amphipathic, having a non-polar end and a polar end.

Fatty acids consist of a hydrocarbon chain with a carboxylic acid at one end.

A 16-C fatty acid: CH3(CH2)14-COO-

Non-polar polar

Fatty acids are carboxylic acids with hydrocarbon chains of 4 to 36 carbons.

A 16-C fatty acid with one cis double bond between C atoms 9-10 may be represented as 16:1 cis D9.

the "n-" nomenclature, –2) the "ω" (omega) system of nomenclature and –3) the "delta" system of nomenclature.

18:3 (Δ9,12,15)

N-

Double bonds in fatty acids usually have the cis configuration. Most naturally occurring fatty acids have an even number of carbon atoms.In animals most common is C16 and C18 palmitic and stearic

Some fatty acids and their common names:14:0 myristic acid; 16:0 palmitic acid; 18:0 stearic acid; 18:1 cis9 oleic acid18:2 cis9,12 linoleic acid18:3 cis9,12,15 -linolenic acid 20:4 cis5,8,11,14 arachidonic acid20:5 cis5,8,11,14,17 eicosapentaenoic acid (an omega-3)

Double bonds in fatty acids usually have the cis configuration. Most naturally occurring fatty acids have an even number of carbon atoms.

Some fatty acids and their common names:14:0 myristic acid; 16:0 palmitic acid; 18:0 stearic acid; 18:1 cis9 oleic acid18:2 cis9,12 linoleic acid18:3 cis9,12,15 -20:4 cis5,8,11,14 arachidonic acid20:5 cis5,8,11,14,17 eicosapentaenoic acid

C

O

O 1

23

4

fatty acid with a cis-9 double bond

Pamitoleic acid , 16:1 W3 fatty acid cis-9- hexadecenoic acid.

Anoic

enoic

Human body can convert Stearic 18:0 to Oleic 18:1 by inserting double bond but is incapable of inserting further double bonds so oleic acid cannot be converted to linoleic 18:2, linolenic 18:3 or arachidonic acid 20:4. Essential fatty acids

There is free rotation about C-C bonds in the fatty acid hydrocarbon, except where there is a double bond.

Each cis double bond causes a kink in the chain.

C

O

O 1

23

4

fatty acid with a cis-9 double bond

In most monounsaturated fatty acids the double bond is between C-9 and C-10 (Δ9), and the other double bonds of polyunsaturated fatty acids are generally Δ12 and Δ15 .

The double bonds of polyunsaturated fatty acids are almost never conjugated (alternating single and double bonds, as in -CH=CH-CH=CH-), but are separated by a methylene group (-CH=CH-CH2-CH=CH-).

The double bonds of almost all naturally occurring unsaturated fatty acids are in the cis configuration.

The nonpolar hydrocarbon chain accounts for the poor solubility of fatty acids in water.

The longer the fatty acyl chain and the fewer the double bonds, the lower the solubility in water

The carboxylic acid group is polar (and ionized at neutral pH), and accounts for the slight solubility of short-chain fatty acids in water.

The melting points of fatty acids and of compounds that contain them are also strongly influenced by the length and degree of unsaturation of the hydrocarbon chain

Melting point α saturation of fatty acid α 1/ unsaturation of fatty acid.

Melting point α length of fatty acid.

Iodine number: the number of grams of iodine absorbed by 100g of fat. The iodine no. is thus a measure of the degree of unsaturation of the fatty acids in fats. Oils like soybean, corn and cottonseed have higher iodine nos. 133,127 and 109 than solid fats like beef fat 42 .However the iodine number gives no indication as to the number of double bonds present in fatty acid molecule.

As a general rule, if the iodine number is in the range of 0-70, then you’re looking at a “fat”;

if the iodine number is greater than 70, you’re looking at an oil

Room temperature lipids in solid or liquid state.

18:0 18: 2 16:0

Triacylglycerols Are Fatty Acid Esters of Glycerol

Formation of an ester:

O O

R'OH + HO-C-R" R'-O-C-R'' + H2O

Saponification: the hydrolysis of fats by alkali is called saponification. This reaction results in the formation of glycerol and salts of fatty acids which are called as soaps.

Soaps are of two types hard and soft.

Hard soaps: common bar soaps are the sodium salts of higher fatty acids.

Soft soaps: potassium salts of higher fatty acids and are marketed as semisolids or pastes.

The fatty acid salts of calcium, magnessium, zinc and lead are however insoluble in water. Calcium soaps are used industrially as lubricating greases.

Zinc soaps are employed in the manufature of talcum powder and other cosmetics.

Lead and magnesium soaps are used in paint industry to hasten the process of drying.

Soaps are important cleansing agents. Their cleansing property is due to their emulsifying action( capacity to render more prolonged the mixing of oil and water).

This is accomplished by the negative charge the soap anion confers on the oil droplet. The electrostatic repulsion then prevents the coalescence of soap and oil droplets into an oil phase.

Saponification

Glycerophospholipids

Glycerophospholipids (phosphoglycerides), are common constituents of cellular membranes.They have a glycerol backbone.Hydroxyls at C1 & C2 are esterified to fatty acids.

C OHH

CH2OH

CH2OH

glycerol

An ester forms when a hydroxyl reacts with a carboxylic acid, with loss of H2O.

C18

N acetyl neuraminidate

Cholesterol

Nutrition and fatty acids

PUFAs and MUFAs

Function1.Food material

2.Food reserve

3.Structural component

4.Heat insulation: fats have high insulating capacity. Stored in sub cutaneous layers.

5.Fatty acid absorbtion: Phospholipids play an iportant role in the absorbtion and transportation of fatty acids.

6.Hormone synthesis: sex harmones, adrenocorticoids, cholic acids and vitamin D are all synthesized from cholestrol.

7.Vitamin carriers: lipids act as carriers of natural fat-soluble vitamins such as vitamin A, D and E

8.Antibiotic agent: Squalamine, a steriod from the blood of sharks has been shown to be an antibiotic and antifungal agents

Repetitive four-step process, called oxidation, by which fatty acids are converted into acetyl-CoA.

The long alkyl chains of their constituent fatty acids are essentially hydrocarbons, highly reduced structures with an energy of complete oxidation (~38 kJ/g) more than twice that for the same weight of carbohydrate or protein.

water of solvation

Because they are insoluble in water, ingested triacylglycerols must be emulsified before they can be digested by water-soluble enzymes in the intestine, and triacylglycerols absorbed in the intestine or mobilized from storage tissues must be carried in the blood bound to proteins that counteract their insolubility.

To overcome the relative stability of the COC bonds in a fatty acid, the carboxyl group at C-1 is activated by attachment to coenzyme A, which allows stepwise oxidation of the fatty acyl group at the C-3, or , position—hence the name oxidation.

Cells that derive energy from the oxidation of fatty acids may obtain those fatty acids from three sources: fats in the diet, fats stored in cells as lipid droplets, and (in animals) fats newly synthesized in one organ for export to another.

Some organisms use all three sources under various circumstances, whereas others obtain fatty acids from only one or two of these sources.

Vertebrates, for example, obtain fats in the diet, mobilize fats stored in specialized tissue (adipose tissue), and convert excess dietary carbohydrates to fats in the liver for export to other tissues

Lipoprotein : VLDL, IDL,LDL,HDL

hormones epinephrine and glucagon, secreted in response to low blood glucose levels

Bound to this soluble protein, the otherwise insoluble fatty acids are carried to tissues such as skeletal muscle,heart, and renal cortex. Here, fatty acids dissociate from albumin and diffuse into the cytosol of the cells in which they will serve as fuel.

Fatty Acids Are Activated and Transported into Mitochondria

Lesser than 12 C can enter mitochondria matrix directly.More than 14 C need to be activated by 3 step reaction called carnitine shuttle different acyl-CoA synthetase isozymes act on fatty acids of short, intermediate, and long carbon chains, respectively

Outer membrane of mitochondria)

thioester linkage between the fatty acid carboxyl group and the thiol group of coenzyme A to yield a fatty acyl-CoA

acyl-carnitine/carnitine transporter

This three-step process for transferring fatty acids into the mitochondrion—esterification to CoA,Transesterification to carnitine followed by transport, andTransesterification back to CoA—links two separate pools of coenzyme A and of fatty acyl–CoA, one in the cytosol, the other in mitochondria.

These pools have different functions. Coenzyme A in the mitochondrial matrix is largely used in oxidative degradation of pyruvate, fatty acids, and some amino acids, whereas cytosolic coenzyme A is used in the biosynthesis of fatty acids

Fatty acyl–CoA in the cytosolic pool can be used for membrane lipid synthesis or can be moved into the mitochondrial matrix for oxidation and ATP production.

Conversion to the carnitine ester commits the fatty acyl moiety to the oxidative fate.

The carnitine-mediated entry process is the rate limiting step for oxidation of fatty acids in mitochondria and, is a regulation point.

Formation of each acetyl-CoA requires removal of four hydrogen atoms (two pairs of electrons and four H) from the fatty acyl moiety by dehydrogenases.

Dehydrogenation of fatty acyl–CoA produces a double bond between the and carbon atoms (C-2 and C-3)three isozymes of acyl-CoA dehydrogenase,very-long-chain acyl-CoA dehydrogenase (VLCAD): 12-18medium-chain (MCAD): 4-14short-chain (SCAD), 4-8All three isozymes are flavoproteins with FAD as a prostheticgroup. FAD E- acceptor - e- transferred to O2 of electron chain -1.5 ATP.

For fatty acyl chains of 12 or more carbons, the reactions are catalyzed by a multienzyme complex associated with the inner mitochondrial membrane, the trifunctional protein (TFP).

Each α subunit contains two activities, the enoyl-CoA hydratase and the -hydroxyacyl-CoA dehydrogenase;

the β subunits contain the thiolase activity.

This tight association of three enzymes may allow efficient substrate channeling from one active site to the next, without diffusion of the intermediates away from the enzyme surface.

When TFP has shortened the fatty acyl chain to 12 or fewer carbons, further oxidations are catalyzed by a set of four soluble enzymes in the matrix.

intramolecular rearrangement