20. LIPID METABOLISM
20.1. Triacylglycerols (Triglycerides)
Triacylglycerols are the esters of trihydric alcohol or glycerol and fatty acid. In monoacylglycerol, one fatty acid is esterified with glycerol and in diacylglycerol two fatty acid are esterified with glycerol. Glycerol is phosphorylated by glycerol kinase at carbon-3 and give rise to glycerol-3-(P). It is found in the tissue. Tri-acylglycerol three fatty acid are esterified with glycerol.
Triacylglycerol is highly rich in reduced carbons. During oxidative reaction of metabolism, they yield large amounts of energy. Complete oxidation of 1g of triacylglycerol yields about 38 kJ energy whereas protein and carbohydrate give rise to only 17 kJ/g. Because of this reason these molecules are the choice of energy storage in animal. Triacylglycerol also provide good insulation.
Diacylglycerol is phosphorylated by kinase at carbon-3 of glycerol and form a phosphatidic acid. Phospholipids are the derivatives of phosphatidic acid. Phosphatidyl acid is an intermediate of synthesis of triacylglycerol as well as phosphoglycerols. Most of the phospholipid have saturated acyl radical (group) at the carbon-1 and unsaturated acyl radical at the carbon-2.
Phosphoglycerides are the membrane lipid. In phosphoglycerides two fatty acids are attached of carbon-1 and carbon-2, Polar or charged group is attached to the carbon-3 through phosphodiester bond. Glycerol is prochiral and asymmetric carbon is absent in it, but after the attachment of phosphate at carbon-3, it converted into chiral compound. Generally phospholipids have C16 or C18 saturated fatty acid at C-1 and C18 or C20 unsaturated fatty acid at Carbon-2.
20.3.1. Types of Phospholipids
1. Phosphatidyl cholin
3. Phosphotidylinosital 4, 5 bisphosphate
5. Phosphotidyl glycerol
Phosphatidyl cholin :
Phosphatidyl cholin is the most abundant phospholipid found in cell membrane. The important function of choline is nervous transmission in the form of acetyl choline. At neutral pH, on phosphatidyl choline net charge is zero.
Phosphatidyl ethanolamine :
It has also net charge zero. Phosphatidylethanolamine prevents adherence in the inner surface of the lungs.
It is formed abundant in most tissues.
It is an important constituent and its main role in signal transduction.
Phosphotidyl Glycerol :
It is a major phospholipid of mitochondria inner membrane.
20.4. Other Lipids :
Lysophopholipid have only one acyl radical. e.g., Lysophosphotidylcholin (lysolecithin). It is found in oxidized lipoprotein and it promote arteriosclerosis.
Plasmalogens are 10% constitute of phospholipid of brain and muscle. It is resemble with the phosphotidyl ethanolamine.
Galactolipid and Sulpholipid
These lipid are found in chloroplast.
One or two galactose residue are connected by glycosidic linkage at Carbon-3 of a diacylglycerol. Galactolipid are present in the thylakoid inner membrane of the chloroplast. They are most abundant membrane lipid.
Sulphonoted glucose residue is joined to a diacylyglycerol by glycosidic linkage. Sulphonate hard group bears a fixed negative charge.
Sphingolipids, which is 4th large class of membrane lipid. Sphingomyelins are found in the brain and nervous tissue in large quantity. Sphinogolipid consist of one molecule of long chain amino alcohol Sphingosine are also called as 4-sphingenine, phosphoric acid, choline and fatty acid. Glycerol is absent in sphingolipid.
The fatty acid which is attached to the NH2 group of carbon-2 by amide linkage this is known as ceramide. All sphingolipids are derivative of ceramide e.g., sphingomyelins. Sphingomyelin have phosphocholine or phosphoethanol amine at their head group. Sphingomyelins are present in plasma membrane of the animal cell. Prominently present in myelin (a membraneous sheath which is surround the exon of neurons) called as sphingomyelin.
20.5.1. Glyosphingolipid :
It is present largely on the outer surface of plasma membrane. One or more sugar connected directly to the carbon-1 of OH of the ceramide. In this lipid phosphate is absent. e.g., Globosides are uncharged Glycosphingolipid which contain two or more sugars such as D glucose, D galactose or N-acetyl D-galactosamine. Cerebrosides and globosides called neutral glycolipid because at pH-7, (neutral) net charge is zero. Gangliosides is a sphingolipid and it contain oligosaccharides at their polar head group. At pH-7 it have negative charge. Sphingolipid at cell surface area sites of biological recognition. Sphingolipid located in the plasma membrane of neurons and thus provide a site of recognition. Sphingolipid determine the types of human blood group because it have certain carbohydrate moieties. Certain gangliosides are largely present in the outer surface of cell and provide point of recognition. Amount and type of gangliosides change during embryonic development in plasma membrane. Phospholipid and sphingolipid are degraded in lysosomes.
Gangliosides are degraded by set of lysosomal enzymes. They are catalyzed step wise and remove the sugar unit and finally yield a ceramide. If mutation or genetic defect in any enzyme occurs, they leads to the accumulation of gangliosides in the cell.
Archaebacteria contain unique membrane lipid. Archaebacteria lines in extreme condition such as high temperature, low pH. Membrane lipid of these bacteria contain long chain about 32 carbon which is branched and hydrocarbon linked at each end of glycerol through ether bonds. Ether bond is more stable to hydrolysis at low pH and high temperature.
Glycolipids are important in nerve tissues and in the cell membrane. Glycolipids are present in every tissue of the body, and largely in nervous tissue such as brain. The glycolipid which is present in animal tissue is glycosphingolipid. The main role of these glycosphingolipid is in nerve transduction.
Steroids are complex derivatives of triterpene. Each type of steroid is compossed of four fused rings called as steroids nucleus. In which ring A, B and C are phenanthrene and ring D is cyclopentane attach to each other. A sterol is a class of steroid characterized by a hydroxyl group at carbon-3.
Cholesterol is best known steroids. It is a precursor of large number of equally important steroids such as—bite acid, adrenocortical hormone, sex hormones, D vitamins, cardiac glycosides. Cholesterol is usually stored within cell as a fatty acid ester.
Cholesterol is a significant constituent of many tissue. Cholesterol is widely distributed in all cells of body especially in nervous tissue. It is major constituent of plasma membrane of plasma lipoproteins. The hydroxyl group on position -3 of cholesterol is esterified with a long chain of fatty acid. It is present in animal but not in plant. Ergosterol is a precusor of vitamin D. It is present in plant and yeast.
20.6.2. Steroid Hormones
Five families of hormones such as androgen, estrogens, progestins, glucocorticoid and mineralocorticoids and bile acid derived from cholesterol.
- Androgens such as - testosterone and estrogen mediate the sexual development and sexual characters in animal.
- Progestin such as - progesterone control the menstrual cycle and pregnancy.
- Glucocorticoids control the carbohydrate, protein and lipid metabolism.
- Mineralo corticoids regulate the salt such as Na+, K+ and Cl– balance in tissue.
- Bile acids consist of cholic and deoxy cholic are detergent molecules secreted by the gall blander, which assist the absorption of lipid in the intestine.
17 b-hydroxysteroid Dehydrogenase-3 the main role of this Estrogen is in the formation of testosterone. Deficiency of this enzyme cause male pseudohermaphroditism.
Steroid hormones carry messages between tissues. Steroids are oxidized derivative of sterols. Steroids hormones move from their site of production to their target tissue through blood stream. They enter in the cells and bind with highly specific protein in the nucleus. After this they trigger changes in the gene expression and metabolism.
Hormones have very high affinity which is sufficient to produce response. Major group of steroid hormones are female and male sex hormones.
Eicosanoids is a family of very potent biological signaling molecules which act as short range messenger. It is known isosanoids because of their origin from 20 carbon molecule known as (polyunsatured fatty acid) Eicosanoic acids.
Eicosanoids are paracrine hormones which act only on nearby cells by the place of their synthesis. It acts locally instead of being transported in the blood to act on cells in other tissue or organs.
20.7.1. Prostaglandines, thromboxans and leukotrienes
Prostaglandins was first isolated from the prostate gland, thus called as prostaglandins. Prostaglands have five carbon ring which is originated from the chain of arachidonic acid. Two group of prostaglandin PGE ether soluble and PGF phosphate buffer soluble. Each group (PGE) have subtype PGE1, 2 and 3.
- Prostaglandins regulate the synthesis of intracellular messenger i.e. cyclic AMP (cAMP). cAMP mediates the action of diverse hormones. Prostaglandin affects the cellular and tissue function.
- Prostaglandin stimulate the contraction of smooth muscles of uterus during menstruation.
- Prostaglandin also affect the blood flow to specific organs.
- Prostaglandin elevate the body temperature and cause inflammation and pain.
Thromboxanes contain six membered ring containing ether. They produces by thrombocytes. (platelets) The main role of thromboxane is formation of blood clot. It reduce the blood flow to site of a clot.
Anti inflammatory drug (NSAIDs) :
Aspirin, ibuprofen and meclofenamate inhibit prostaglandin H2 synthesis. Which catalyses the early step in the path way from arachidonate to prostaglandins and thromboxans.
Leukotrienes are hydroxy fatty acid derivative of arachidonic acid. Leukotrienes do not contain a ring structure. Leukotrienes is 1st found in leukocytes. Leukotrienes are distinguished by containing a conjugated triene double-bond arrangement. They are powerful biological molecules. e.g., Leukotriene D4, derived from leukotriene A4.
It induces the contraction in the muscle lining to the lung. Leukotrienes causes asthmatic attacks because of the over production.
Body contain a variety of lipids stored in its structure which performs a variety of functions. Fatty acids are the storage material which produces a large amount of energy upon oxidation. Fats transported inside the body in the form of lipoproteins which can be very low density lipoproteins (VLDL), low density lipoproteins (LDL) and high density lipoproteins (HDL).