Dental Biochemistry 1- (8)

Chemistry of Lipids

Definition of lipids • Lipids may be defined as compounds

which are relatively insoluble in water, but freely soluble in nonpolar organic solvents like benzene, chloroform, ether, hot alcohol, acetone, etc.

Function of lipids

1. Storage form of energy (triglycerides).

2. Structural components of bio-membranes (phospholipids and cholesterol).

3. Metabolic regulators (steroid hormones and prostaglandins).

4. Help in absorption of fat soluble vitamins (A, D, E and K).

5. Improve taste and palatability to food.

Classification of lipids

Based on the chemical nature, lipids are classified into:

I. Simple lipids They are esters of fatty acids with glycerol or

other higher alcohols. They are sub-classified as:

a. Triacylglycerol or triglycerides or neutral fat.

b. Waxes.

II. Compound lipids

• They are fatty acids esterified with alcohol; but in addition they contain other groups.

• Depending on these extra groups, they are sub-classified as:

a. Phospholipids containing phosphoric acid.

b. Nonphosphorylated lipids.

III. Derived lipids: • They are compounds which are derived from

lipids or precursors of lipids.

• E.g. fatty acids, steroids, prostaglandins, …etc.

IV. Lipids complexes to other compounds:

Proteolipids and lipoproteins.

Fatty acids

• Fatty acids, are included in the group of derived lipids.

• It is the most common component of lipids in the body.

• Fatty acids are aliphatic carboxylic acids and have the general structural formula, R-COOH, where COOH (carboxylic group) represents the functional group.

• Depending on the R group (the hydrocarbon chain), the fatty acids may vary.

• Each animal species will have characteristic pattern of fatty acid composition. Thus, human body fat contains 50% oleic acid, 25% palmitic acid, 10% linoleic and 5% stearic acid.

• The carbon atoms of fatty acids are numbered as C1, C2 etc. starting from the COOH group. Or, starting from the methyl end, the carbon atoms may be numbered as omega (ῳ)-1,2,3, etc.

• 6 5 4 3 2 1

CH3 – CH2 – CH2 – CH2 – CH2 – COOH

ῳ1 ῳ2 ῳ3 ῳ4 ῳ5

Classification of fatty acids

1. Depending on Total No. of carbon atoms:

a. Even chain, having carbon atoms 2,4,6 and similar series. Most of the naturally occurring lipids contain even chain fatty acids.

b. Odd chain, having carbon atoms 3,5,7, etc. Odd numbered fatty acids are seen in microbial cell walls. They are also present in milk.

2. Depending on Length of hydrocarbon chain:

a. Short chain with 2 to 6 carbon atoms e.g. Acetic acid (2 C) CH3-COOH Butyric acid (4 C) CH3-CH2-CH2-COOH b. Medium chain with 8 to 14 carbon atoms. c. Long chain with 16 and above, usually up to 24

carbon atoms. e.g. Palmitic acid (16 C) CH3-(CH2)14- COOH

Stearic acid (18 C) CH3-(CH2)16- COOH

Depending on Nature of hydrocarbon chain:

1. Saturated fatty acids

• They have the general structural formula

CH3-(CH2)n-COOH. contain single bond.

• They are named by adding the suffix ‘anoic’ after the hydrocarbon.

• The two carbon acetic and 4 carbon butyric acid are important metabolic intermediates.

• C16 palmitic and C18 stearic acids are most abundant in body fat.

2. Unsaturated fatty acids

• They are named by adding the suffix ‘enoic’ after the systematic name.

• which may be sub- classified into Mono-unsaturated (mono-enoic) having single double bond or polyunsaturated (poly-enoic) with 2 or more double bonds.

Clinical significance of PUFA • Linoleic and linolenic acids are polyunsaturated

fatty acids. Linoleic acid has 2 double bonds; Linolenic acid has 3 double bonds and Arachidonic acid has 4 double bonds.

• Unsaturated fatty acids are also designated ῳ3 (omega 3) family (Linolenic acid); ῳ6 family (Linoleic and Arachidonic acids) and ῳ9 family (Oleic acid).

• Arachidonic acid is the precursor of prostaglandins.

• The pentaenoic acid present in fish oil is of great nutritional importance (ῳ3 unsaturated fatty acid).

BILOGICAL CLASSIFICATION 1- Essential fatty acids

• Poly unsaturated fatty acids with more than double bond and not synthesize by mammals.

• Linoleic (ὠ6, 18C, two double bonds) and Linolenic acid (ὠ3, 18C, three double bonds) are the only fatty acids which cannot be synthesized in the body.

• They have to be provided in the food; hence they are essential fatty acids.

• Arachidonic acid can be formed, if the dietary supply of linoleic acid is sufficient.

N.B. Eicosanoids are 20C compounds derived from arachidonic acid.

• Normal dietary allowance of PUFA is 2-3% of total calories.

2- Non-essential fatty acids Saturated fatty acids or fatty acids contain one double

bond and synthesize by mammals.

e.g. Stearic and Oleic acid.

Neutral fats or Triacylglycerols (TAG) or Triglycerides

• These are esters glycerol with fatty acids.

1. Nomenclature of Carbon Atoms: • The carbon atoms of glycerol are designated as α, β

and ἀ or as 1, 2, 3

α (1) CH2-O-CO-R

I

Β (2) R-CO-O-C-H

I

ἀ (3) CH2-O-CO-R

2. Storage of energy as fat:

• The triglycerides are the storage form of lipids in the adipose tissue.

• When stored as TAG, water molecules are repelled and space requirement is minimal.

• Excess fat in the body leads to obesity.

6. Rancidity of fat:

• Fats and oils have a tendency to become rancid.

• The term rancidity refers to the appearance of an unpleasant smell and taste for fats and oils.

• PUFA are more easily oxidized; so vegetable oils with a high content of PUFA are usually preserved with addition of antioxidants.

• Fats and oils are preferred cooking media. However, overheating and repeated heating would lead to the formation and polymerization of cyclic hydrocarbons.

• These will impart an unpleasant taste and color to the oil.

• Coconut oil having medium chain saturated fatty acids will withstand such polymerization.

Prostaglandins (PGs) • PGs are present in almost all tissues. • They are the most potent biologically active

substances; as low as one nanogram/ml of PG will cause smooth muscle contraction.

• The diverse physiological roles of prostaglandins confer on them the status of local hormones.

• depending on number of double bonds on the side chains they are denoted by a subscript after the capital letter, e.g. PGE1, PGE2, PGE3, etc

• In most tissues, PGE increases cAMP (cyclic AMP) level.

Effects of PGs on CVS: (cardiovascular system) • Prostacyclin or PG12 is synthesized by the vascular

endothelium. Major effect is vasodilatation.

• It also inhibits platelet aggregation and has a protective effect on vessel wall against deposition of platelets.

• Thromboxane (TXA2) is the main PG produced by platelets.

• The major effects are vasoconstriction and platelet aggregation.

• Prostacyclin and thromboxane are opposing in activity.

• Prostaglandins increase the contractility and lowers the blood pressure.

• Hence, it may be used in the treatment of hypertension.

Effects on ovary and uterus:

• PGF2 stimulates the uterine muscles.

• Hence, PGF2 may be used for medical termination of pregnancy.

• Yet another use is in inducing labor and arresting postpartum hemorrhage.

• Effects on respiratory tract • PGE is a potent bronchodilator.

• PGE is used in aerosols for treating bronchospasm.

Phospholipids

• They contain glycerol, fatty acids and a nitrogenous base.

• They have both hydrophobic and hydrophilic portion in their molecule

Biomembranes: • The molecules align themselves to form

monolayers with the polar heads pointing in one direction and the nonpolar tails in the opposite direction.

• In vivo, they act as pulmonary surfactants.

Liposomes: • Liposomes are microscopic spherical vesicles.

• When mixed in water under special conditions, the phospholipids arrange themselves to form a bilayer membrane which encloses some of the water in a phospholipid sphere.

• Drugs, proteins, enzymes, etc. may be encapsulated by the liposomes which act as carriers for these substances to target organs.

• Liposomes have important applications in cancer chemotherapy, antimicrobial therapy, gene therapy, vaccines and diagnostic imaging.

• DIGESTION OF LIPIDS

• The major dietary lipids are triacylglycerol, cholesterol and phospholipids.

• Digestion in Stomach

• i. The lingual lipase from the mouth enters stomach along with the food. It has an optimum pH of 2.5-5. The enzyme therefore continues to be active in the stomach. It acts on short chain triglycerides (SCT). SCTs are present in milk butter, ghee and coconut oil. The action of lingual lipase is observed to be more significant in the newborn infants.

• ii. Gastric lipase is acid stable, with an optimum pH about 5.4. It is secreted by Chief cells, the secretion is stimulated by Gastrin.

• Digestion in Intestines • Emulsification is a pre-requisite for digestion of lipids.

The lipids are dispersed into smaller droplets; surface tension is reduced; and surface area of droplets is increased.

• Bile Salts are Important for Digestion of Lipids

• The bile salts present in the bile (sodium glycocholate and sodium taurocholate) lower surface tension. They emulsify the fat droplets in the intestine. The emulsification increase the surface area of the particles for enhanced activity of enzymes.

• Lipolytic Enzymes in Intestines

• Pancreatic lipase with Co-lipase will further hydrolyze the neutral fats. The bile (pH 7.7) entering the duodenum serves to neutralize the acid come from the stomach and provides a pH favorable for the action of pancreatic enzymes.

• Digestion of Triglycerides

• i. Pancreatic Lipase can hydrolyze the fatty acids at

the 1st and 3rd carbon atoms of glycerol. The

products are 2-mono acylglycerol (2-MAG) and two

fatty acid molecules.

• ii. Then an isomerase shifts the ester bond from

position 2 to 1. The bond in the 1st position is then

hydrolyzed by the lipase to form free glycerol and

fatty acid.

• iii. The major end products of the digestion of TAG

are 2-MAG, 1-MAG, glycerol and fatty acids.

Thus, digestion of TAG is partial (incomplete).

• Absorption of lipids by cells in the small intestine.

Chylomicron: • A small fat globule composed of protein and

lipid.

• The chylomicrons are synthesized in the mucosa (the lining) of the intestine.

• Chylomicrons are found in the blood and lymphatic fluid where they serve to transport fat from its port of entry in the intestine to the liver and to adipose (fat) tissue.

• After a fatty meal, the blood is so full of chylomicrons that it looks milky.

• Fate of absorbed Fat • i. The absorbed (exogenous) triglycerides are

transported in blood as chylomicrons. They are taken up by adipose tissue and liver.

• ii. Liver synthesizes endogenous triglycerides. These are transported as VLDL (very low density lipoproteins) and are deposited in adipose tissue.

• iii. Triglycerides In adipose tissue are lysed to produce free fatty acids. In the blood, they are transported, complexed with albumin.

• iv. Free fatty acids are taken up by the cells, and are then oxidized by β-oxidation to get energy.