1 Chemistry of Lipids and their Biomedical Importance
1 Chemistry of Lipids and their Biomedical Importance Chapter-04 2/24/2021
What are Lipids? 2 • The lipids constitute a very important heterogeneous group of organic substances in plant and animal tissues, and related either actually or potentially to the fatty acids. • Chemically they are various types of esters of different alcohols. In addition to alcohol and fatty acids, some of the lipids may contain phosphoric acid, nitrogenous base and carbohydrates. 2/24/2021
Bloor’s Criteria 3 According to Bloor, lipids are compounds having the following characteristics: • They are insoluble in water. • Solubility in one or more organic solvents, such as ether, chloroform, benzene, acetone, etc, so called fat solvents. • Some relationship to the fatty acids as esters either actual or potential. • Possibility of utilization by living organisms. 2/24/2021
4 • Thus, lipids include fats, oils, waxes and related compounds. • An oil is a lipid which is liquid at ordinary temperature. • Distinction between fats and oils is a purely physical one. • Chemically they are all esters of glycerol with higher fatty acids. 2/24/2021
Polyunsaturated (Polyethenoid)fatty acids: 5 • There are three polyunsaturated fatty acids of biological importance. • Linoleic acid series (18 : 2; 9, 12) It contains two double bonds between C 9 and C 10; and between C 12 and C 13. Their general formula is Cn. H 2 n– 3 COOH. Dietary sources: Linoleic acid is present in sufficient amounts in peanut oil, corn oil, cottonseed oil, soyabean oil and egg yolk. 2/24/2021
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Linolenic acid series (18 : 3; 9, 12, 15) 7 • It contains three double bonds between 9 and 10; 12 and 13; and 15 and 16. • Their general formula is Cn. H 2 n– 5 COOH. • Dietary Source: Found frequently with linoleic acid, but particularly present in linseed oil, rapeseed oil, soybean oil, fish visceras and liver oil (cod liver oil). 2/24/2021
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Arachidonic acid series (20 : 4; 5, 8, 11, 14) • It contains four double bonds. • Their general formula: Cn. H 2 n– 7 COOH • Dietary source: Found in small quantities with linoleic acid and linolenic acid but particularly found in peanut oil. • Also found in animal fats including Liver fats. 2/24/2021 9
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Functions of EFA: (Biomedical Importance) 11 • Structural elements of tissues: • Polyunsaturated fatty acids occur in higher concentration in lipids associated with structural elements of tissues. • Synthesis of prostaglandins and other compounds: Prostaglandins are synthesised from Arachidonic acid by cyclooxygenase enzyme system. • Leukotrienes are conjugated trienes formed from arachidonic acid in leucocytes by the Lipoxygenase pathway. 2/24/2021
What is the difference between lymphocytes and monocytes? • Monocytes are large, spherical cells that make up 2 to 8% of circulating WBCs. • Monocytes can enter peripheral tissues to become tissue macrophages which can engulf large particles and pathogens. • Lymphocytes , slightly larger than RBCs, make up 20 to 30% of circulating WBCs. They migrate in and out of the blood 2/24/2021 12
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• Structural element of mitochondrial membrane: 15 • A deficiency of EFA causes swelling of mitochondrial membrane and reduction in efficiency of oxidative phosphorylation. • This may explain for increased heat production noted in EFA deficient animals. 2/24/2021
Serum level of cholesterol 16 • Fats with high content of polyunsaturated fatty acids tends to lower serum level of cholesterol. • Effect on clotting time: Prolongation of clotting time is noted in ingestion of fats rich in EFA. 2/24/2021
Effect on fibrinolytic activity 17 • An increase in fibrinolytic activity follows the ingestion of fats rich in EFA. Role of EFA in fatty liver: Deficiency of EFA produces fatty liver 2/24/2021
• Role in vision 18 • Docosahexaenoic acid (22: 6 n-3) is the most abundant polyenoic fatty acids present in retinal photoreceptor membranes. • Docosahexaenoic acid is formed from dietary linolenic acid. • It enhances the electrical response of the photoreceptors to illumination. • Hence linolenic acid is necessary in the diet for optimal vision. 2/24/2021
CLINICAL ASPECT Human deficiency: Some cases of Eczema like dermatitis, Degenerative changes in arterial wall and Fatty liver in may be due to EFA deficiency. There also some reports that administration of EFA in such cases may produce: – Some improvement of eczema in children kept on skimmed milk, – Prevent fatty liver (some cases) – Lowering of cholesterol levels. Infants and babies with low fat diet develop typical skin lesions 2/24/2021 which has shown to be improved with EFA (linoleic acid). • • • 19
Docosahexaenoic acid: DHA (W 3, 22: 6) 20 • Docosahexaenoic acid (DHA) is a polyunsaturated fatty acid which is synthesized from α-linolenic or obtained directly from dietary fish oil. • This fatty acid is present in high concentrations in retina, cerebral cortex, tastes and sperms. • DHA is particularly needed for development of the brain and retina and is supplied via the placenta and milk. 2/24/2021
21 • In EFA deficiency, nonessential polyenoic acids of the W 9 family replace the essential fatty acids in phospholipids (PL), other complex lipids and membranes. • Clinical Aspect Low blood levels of DHA have been reported in patients with Retinitis Pigmentosa 2/24/2021
ALCOHOLS • Alcohols contained in the lipid molecule includes glycerol, cholesterol and the higher alcohols, e. g. Cetylalcohol, C 16 H 33 COOH (usually found in waxes). 1. Glycerol: Glycerol is commonly called as “glycerin” it is the simplest trihydric alcohol as it contains three hydroxyl groups in the molecule 2. It is colourless oily fluid with a sweetish taste. 3. It is miscible with water and alcohol in all proportions but is almost insoluble in ether. 2/24/2021 22
Cetylalcohol, C 16 H 33 COOH 23 • Cetyl alcohol also known as hexadecan-1 -ol and palmityl alcohol, is a fatty alcohol with the formula CH 3(CH 2)15 OH. • At room temperature, cetyl alcohol takes the form of a waxy white solid or flakes. • The name cetyl derives from the whale oil (Latin: cetus) from which it was first isolated. 2/24/2021
Source Industrial 24 • It is obtained as a by-product of soap manufacture. • It is also obtainable in the fermentation of glucose by changing conditions in such a way as to decrease the formation of CO 2 and alcohol. 2/24/2021
Physiological 25 • Endogenous source: • Main source is from lipolysis of fats in adipose tissue. • Exogenous source: Dietary Approx. 22 per cent of glycerol directly absorbed to portal blood from the gut 2/24/2021
Uses In medicine 26 • Nitroglycerine is used as a vasodilator. • • Glycerol therapy in cerebrovascular (CV) diseases reduces cerebral oedema 2/24/2021
Physiological 27 • In body, glycerol has a definite nutritive value. • It can be converted to glucose/and glycogen, the process called as gluconeogenesis 2/24/2021
Steroids and Sterols 28 • 1. The steroids are often found in association with fat. • 2. They may be separated from the fat, after the fat is saponified, since they occur in unsaponifiable residue. • 3. All of the steroids have a similar cyclic nucleus resembling phenanthrene (ring A, B and C) to which a cyclopentane ring (ring D) is attached. • It is designated as cyclopentano perhydro-phenanthrene nucleus. 2/24/2021
29 • Methyl side chains occur typically at positions 10 and 13 (constituting carbon atoms 19 and 18 respectively). • 5. A side chain at position 17 is usual. • If the compound has one or more –OH groups and no carbonyl or carboxyl groups, it is called a ‘sterol’ and the name terminates in –”ol”. • Most important sterol in human body is cholesterol. 2/24/2021
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Cholesterol Structure 31 • Cholesterol is the most important sterol in human body. • Its molecular formula is C 27 H 45 OH. • It possesses “cyclo-pentane-perhydro-phenanthrene nucleus”. • It has an –OH group at C 3. • It has an unsaturated double bond between C 5 and C 6. • It has two –CH 3 groups at C 10 and C 13. • It has an eight carbon side chain attached to C 17. 2/24/2021
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OTHER STEROLS OF BIOLOGICAL IMPORTANCE • 1. 7 -Dehydrocholesterol It is an important sterol present in the skin. • This differs from cholesterol only in having a second double bond, between C 7 and C 8 • Source: In man, 7 -dehydrocholesterol may be obtained partly by synthesis from cholesterol in skin and/or intestinal wall. https: //www. google. com/search? q=7 Dehydrocholesterol&tbm=isch&ved=2 ah. UKEwjntbvk_p. Ho. Ah. Wy 2 OAKHbek. BYYQ 2 -c. Ceg. QIABAA&oq=7 Dehydrocholesterol&gs_l=img. 3. . 0 i 67 j 0 l 6 j 0 i 30 l 3. 132217. . 134439. . . 0. 0. 238. 2 -1. . . 0. . 1. . gwswizimg. 3 Kno. Pgm. Mmw 0&ei=j. Z 9 o. Xqe 7 Br. Kxgwe 3 y. Zaw. CA&bih=676&biw=1247&rlz=1 C 1 CHBD_en. PK 777&hl=en#i mgrc=39 Z 1 wz. BECCu. Te. M 2/24/2021 36
Biomedical Importance 37 • In the epidermis of skin, UV rays of sunshine change 7 -dehydrocholesterol (pre-cholecalciferol) to cholecalciferol (vitamin D 3). • Hence 7 -dehydrocholesterol is called as provitamin. D 3. • This explains the value of sunshine in preventing rickets, a disease produced from vitamin D deficiency. 2/24/2021
Ergosterol 38 • It is a plant sterol, first isolated from ergot, a fungus of rye and later from yeast and certain mushrooms. • Structurally this sterol has the same nucleus as 7 dehydrocholesterol but differs slightly in its side chain • https: //www. google. com/search? q=Ergosterol&tbm=isch&ved=2 ah. UKEwjfl. J 6 l_5 Ho. Ah. UF 7 e. AKHZNPD 1 g. Q 2 c. Ceg. QIABAA&oq=Ergosterol&gs_l=img. 3. . 0 i 67 j 0 l 9. 275044. . 275978. . . 0. 0. 248. 24 8. 2 -1. . . 0. . 1. . gws-wiz-img. 4 Ww 67 z. Pbp. G 4&ei=FKBo. Xt 6 OYXagwe. Tn 73 ABQ&bih=676&biw=1247&rlz=1 C 1 CHBD_en. PK 777&hl=en#imgrc=d. BSg ur_c. W 7 Qxx. M&imgdii=Kbzz. QKgxv 0 n. Mh. M 2/24/2021
Biomedical Importance 39 • When irradiated with UV rays (long wave 265 μm) ergosterol is changed to vitamin D 2 by the opening of the ring B of the sterol. • Hence ergosterol is called as Provitamin-D 2, over irradiation may produce toxic products 2/24/2021
Emulsification 40 • Emulsions of fat may be made by shaking vigorously in water and by emulsifying agents such as gums, soaps and proteins which produce more stable emulsions. Biomedical Importance of Emulsification The emulsification of dietary fats in intestinal canal, brought about by bile salts, is a prerequisite for digestion and absorption of fats 2/24/2021
IDENTIFICATION OF FATS AND OILS 41 • Saponification Number Definition: The number of mgs of KOH required to saponify the free and combined FA in one gram of a given fat is called its saponification number. • Acid Number Definition: • Number of mgs of KOH required to neutralize the fatty acids in a gm of fat is known as the acid number. 2/24/2021
42 • Polenske Number Definition: It is the number of millilitre of 0. 1 normal KOH required to neutralize the insoluble fatty acids (those not volatile with steam distillation) from 5 gram of fat. • Reichert-Meissl Number Definition: It is the number of millilitres of 0. 1 (N) alkali required to neutralize the soluble volatile fatty acids distilled from 5 gm of fat. • Iodine Number Definition: • Iodine number is defined as the number of grams of iodine absorbed by 100 gm of fat. 2/24/2021
Clinical aspect 43 Fabry’s disease: An inherited disorder, a lipid storage disease (lipidosis). • Inheritance: X-linked dominant, full symptoms only in males. • Enzyme deficiency: α-galactosidase. The enzyme is found normally in liver, spleen, kidney, brain and small intestine. 2/24/2021
44 • Skin rash (reddish purple), Pain in lower extremities (painful neuropathy), Lipid accumulates in the endothelial lining of blood vessels, may produce vascular thrombosis. • Progressive renal failure–due to extensive deposition of lipids in glomeruli. • Occasionally manifestations of cardiac enlargement. • Eye involvement: Corneal opacities, cataracts, vascular dilatation. 2/24/2021
Krabbe’s Disease • 45 • An inherited disorder of lipid metabolism, a lipid storage disease(lipidosis) • Enzyme deficiency: Galacto-cerebrosidase (β-galactosidase). The enzyme normally catalyzes the hydrolysis of galactocerebrosides and it splits the linkage between ceramide and galactose • Nature of lipid accumulating: Galactosyl ceramide Clinical manifestations: – Severe mental retardation in infants – Total absence of myelin in central nervous system – 2/24/2021 Globoid bodies found in white matter of brain
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48 • Exercise on page 64 section 2 • MCQs are included in exam 2/24/2021
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