1st year MBBS Biochem Lecture Lipid Metabolism.pptx

This is a biochemistry lecture for undergraduate medical students on lipid metabolism

1. Chemistry of Lipids

2. Lipids: Chemically lipids are various types of esters of different alcohols. They are insoluble in water. Solubility in one or more organic solvents, such as ether, chloroform, benzene, acetone, etc, so called fat solvent. An oil is a lipid which is liquid at ordinary temperature. Distinction between fats and oils is purely physical one.

3. Biomedical Importance Fuel energy per gm (9.1 kcal/gm) Stored in the body Exert an insulating effect Building biological active materials. EFA are essentials in the diet for normal health and growth. The nervous system is particularly rich in lipids. Vit A, D, E and K are fat soluble. Important constituents of many natural membranes e.g. Cell walls & cell organelles like mitochondrion, etc. Lipoproteins are also carriers of triglycerides, cholesterol and PL in the body .

4. Classification of Lipids Simple Lipids Esters of fatty acids with various alcohols: Neutral fats ( Triacylglycerol , TG): These are triesters of fatty acids with glycerol Waxes are esters of fatty acids with higher mono- hydroxy aliphatic alcohols. True waxes are esters of higher fatty acids with cetyl alcohol (C 16 H 33 OH) or other higher straight chain alcohols.

5. II. Compound Lipids Esters of fatty acids containing groups, other than, and in addition, to an alcohol and fatty acids. E.g , Phospholipids: They are substituted fats containing in addition to fatty acid and glycerol, a phosphoric acid residue, a nitrogenous base and other substituents. Glycerol phospholipids—alcohols is glycerol Sphingo phospholipids—alcohols is sphingosine.

6. b. Glycolipids : Lipids containing carbohydrate moiety are called glycolipids . They contain a special alcohol called sphingosine or sphingol and nitrogenous base in addition to fatty acids but does not contain phosphoric acid or glycerol. These are of two types: Cerbrosides Gangliosides

7. c . Sulpholipds : Lipids characterised by possessing sulphate groups: Aminolipids ( Proteolipids ) Lipoproteins: Lipids as prosthetic group to proteins Derived Lipids Derivatives obtained by hydrolysis of simple and compound lipids, which still possess the general characteristics of lipids.

8. e.g. 1.Fatty acids: may be saturated, unsaturated or cyclic. 2.Alcohols 3.Cholesterol and other steroids including sterols 4. Vitamin A, D, E & K . 5.Carotenoids 6.Monoglycerides ( Monoacylglycerol ) and Diglycerides ( Diacyglycerol ) 7.Eicosanoid compounds (including prostaglandins, prostacyclins,thromboxanes,leukotrienes & lipoxins ) 8.Terpenes

9. Simple Lipids Neutral fats (TG) are all triesters of the trihydric alcohol, glycerol with various fatty acid.

10. COMPOUND LIPIDS

11. Classification: Classification given is based on the type of alcohol present: - Glycerophospholipid e.g. Phosphatidic acids Phosphatidyl choline — Lecithin Phosphatidyl — Serine Phosphatidyl Ethanolamine— Cephalins Plasmalogens Cardiolipin Phosphinositides - Sphingophospolipids

12. ( i ) Phosphatidic acids:- In these acids, one of the fatty acids of a triacylglycerol is replaced by H 2 PO 4 .These are present in compounds of all glycerophospholipids. They are present in cells in small amounts only.

13. (ii) Phosphatidyl Choline (Lecithin) It is widely distributed in animals in liver, brain, nerve tissues, sperm and egg-yolk, having both metabolic and structural functions. Plants, seeds and sprouts. Synthetically, on hydrolysis, lecithin yields; Glycerol fatty acids, phosphoric acid (d) Nitrogenous base choline

14. (iii) Phosphatidyl Serine: Cephalin like contains amino acid serine in place of ethanolamine found in brain and nervous tissues and small amount in found in blood.

15. (iv) Phosphatidyl Ethanolamine ( Cephalins ) If in Lecithins , base ethanolamine replaces choline . Particularly rich in brain and nervous tissues.

16. (v) Plasmalogens : 10 per cent of total phosphlipids of brain and nervous tissue, muscle and mitochondria. These compounds yield on hydrolysis (a) one molecule each of long chain aliphatic aldehyde , (b) a fatty acid, (c) glycerol—PO4, and (d) a nitrogenous base which is usually ethanolamine, but may be sometimes choline .

17. Structure of a Plasmalogen: Plasmalogens appear to be resistant to phospholipases . One of the related compounds is the platelet activating factor which is released from basophils .

18. (vi). Cardiolipin Found in mitochondria (inner membrane) and bacterial wall. It is diphosphatidyl glycerol.

19. Other Phospholipids of Biological Importance: Phosphatidyl Inositol ( Lipositols ) Inositol is an alcohol, formula C 6 H 12 O 6 It replaces the base choline of lecithin, occur in Brain and nervous tissues, in soybeans, in plant phosphlipids .

20. Spingomyelins ( Phosphatidyl sphingosides ) Found in large quantities in brain and nervous tissues, and very small amount in other tissues. It does not contain glycerol. In place of glycerol, it contains an 18 carbon unsaturated amino alcohol called ‘ sphingosine ’( sphingol ). Sphingosine molecule in which a fatty acid acyl group is substituted on the –NH2 group is called as ceramide and when a phosphate group is attached to ceramide, it is called ceramide phosphate.

21. Sphingomyelin

22. When choline is split off from sphingomyelin , ceramide phosphate is left. Spingomyelinase is the enzyme which hydrolyses sphingomyelin to form ceramide and phosphoryl choline . Clinical Aspect of Sphingomyelins Niemann -Pick Disease Large accumulations of sphingomyelins may occur in brain, liver and spleen of some persons suffering from Niemann -Pick disease. Inherited disorder Inheritance: Autosomal recessive

23. Enzyme defect: Deficiency of the enzyme sphingo-myelinase , a lysosomal enzyme. Clinical features: Affects children, gradual enlargement of abdomen, hepatomegaly , splenomegaly, progressive mental deterioration. Other lipids and cholesterol are usually normal or may be slightly elevated. Prognosis: 80 % of infants die within 2 years.

24. Phospholipase A2 is found in pancreatic fluid and snake venom; phospholipase C is one of the major toxins secreted by bacteria; and phospholipase D is known to be involved in mammalian signal transduction

25. Functions of Phospholipids: Structural : Participate in the lipoprotein, cell walls, membranes, myelin sheath, mitochondria and microsomes. Role in enzyme action : Certain enzymes require tightly bound phospholipids for their actions, e.g. Mitochondrial enzyme system. Role in blood coagulation : Conversion of prothrombin to thrombin by active factor X, and also in the activation of factor VIII by activated factor IX. Platelets provide the chief source of PL which contribute to intrinsic blood coagulation process is called platelet factor 3.

26. Role in lipid absorption in intestine: Lecithin lowers the surface tension. Role in transport of lipids from intestines: As lipoprotein complex. Role in transport of lipids from liver Role in electron transport: PL help to couple oxidation with phosphorylation and maintain electron transport enzymes in active conformation Lipotropic action of lecithin: Choline acts as a lipotropic agent as it can prevent formation of fatty liver.

27. Ion transport and secretion Membrane phospholipids as source of arachidonic acid: Phospholipids of membrane are hydrolysed by phospholipase A 2 and provide the unsaturated fatty acid arachidonic acid, which is utilised for synthesis of prostaglandins and leukotrienses . Enzyme lipoprotein lipase and triacylglycerol lipase. Role of phosphatidyl inositides metabolite in Ca ++ dependent hormone action. Insulation

28. Sphingolipidoses : A group of  hereditary  metabolic disorders featuring local accumulations of fatty material( glycolipids  and phospholipids) in various parts of the body. These cannot be broken down further because of the absence of the necessary  enzymes.