Lipid Metabolism Revision Notes PDF

Important notes on lipid metabolism A. Fatty acid synthesis 1. Mechanisms of fatty acid synthesis include: Cytoplasmic De Novo pathway – Microsomal pathway for chain elongation. 2. Requirements of cytoplasmic pathway of fatty acid synthesis (Acetyl CoA – NADPH+H+ - Fatty acid synthase comple...

Important notes on lipid metabolism A. Fatty acid synthesis 1. Mechanisms of fatty acid synthesis include: Cytoplasmic De Novo pathway – Microsomal pathway for chain elongation. 2. Requirements of cytoplasmic pathway of fatty acid synthesis (Acetyl CoA – NADPH+H+ - Fatty acid synthase complex) 3. Sources of NADPH+H+ needed for fatty acid synthesis: - Hexose monophosphate pathway (main source) - Action of cytoplasmic isocitrate DH - Action of malic enzyme on malate 4. Rection of conversion of acetyl CoA to malonyl CoA Acetyl CoA carboxylase Acetyl COA Malonyl CoA ATP CO2 Biotin ADP+Pi 5. Propionyl CoA acts as a primer instead of acetyl CoA for synthesis of odd number FAs while acetyl CoA is used during synthesis of even number FAs. 6. Acetyl CoA used as a primer forms carbon atoms 15 and 16 of palmitate. 7. Sphingosine alcohol is synthesized from palmitoyl CoA and serine amino acid. 8. Acetyl CoA carboxylase is the key regulatory enzyme of fatty acid synthesis. 9. Requirements for microsomal pathway for fatty acid elongation include: Fatty acid (C10 – C16) – Malonyl CoA – NADPH+H+) 10. Microsomal pathway of fatty acid synthesis differs from cytoplasmic pathway in: - It uses coenzyme A instead of acyl carrier protein - It uses separate enzymes instead of the enzyme complex 11. Essential fatty acids include linoleic and linolenic fatty acids only 12. Arachidonic fatty acid is synthesized in the body from linoleic fatty acid 13. Fates of acetyl CoA: - Oxidation by kreb's cycle to produce energy. - Lipogenesis: formation of FAs. - Ketogenesis: formation of ketone bodies. - Cholesterol synthesis: which is the precursor of: Bile acids - Vitamin D3 - Steroid hormones - Formation of acetyl choline B. Fatty acid oxidation 14. Beta oxidation of fatty acids occurs in the mitochondria 15. Activation of fatty acid to acyl CoA ATP AMP+PPi Fatty acid Acyl CoA COASH 1 16. Calculate the energy produced from complete oxidation of palmitic acid (16 carbons) and stearic acid (18 carbons) Energy = [(N/2 - 1) x 5 ATP] + [N/2 x 12 ATP] - 2 ATP N = number of carbon atoms So, In case of palmitic acid = [(16/2 -1) X 5] + [16/2 X 12] – 2 = 129 ATP case of stearic acid = [(18/2 -1) X 5] + [18/2 X 12] – 2 = 146 ATP 17. Oxidation of odd number fatty acids gives acetyl CoA and propionyl CoA which is converted to succinyl CoA. While oxidation of even number fatty acids gives only acetyl CoA molecules. 18. The fatty acid which must undergoes alpha oxidation before beta oxidation is phytanic acid because it contains a methyl group at the beta carbon which prevents the beta oxidation. C. Ketone bodies metabolism & lipolysis 19. Ketone bodies include acetone, acetoacetic acid and beta hydroxybutyric acid. 20. Ketone bodies are synthesized only in the liver inside the mitochondria. 21. The only organ that can’t use ketone bodies as a source of energy is the liver because it doesn’t contain enzymes for oxidation of ketone bodies. 22. Activation of ketone bodies for acetoacetate during ketolysis occurs either by acetoacetyl CoA synthetase enzyme or by succinyl CoA. 23. Importance of ketone bodies: Ketone bodies are the main source of energy in extrahepatic tissues during fasting, starvation or carbohydrate deficiency. 24. The key regulatory enzyme for lipolysis is the hormone sensitive lipase 25. Products of lipolysis include glycerol and fatty acids 26. The utilization of glycerol depends upon whether such tissues possess glycerol kinase or not as the liver. D. Cholesterol metabolism 27. Importance of Cholesterol: - Structural component of cell membrane. Synthesis of steroid hormones, vitamin D3 and bile acids. 28. All carbon atoms of cholesterol are synthesized from Acetyl CoA. 29. HMG-CoA reductase is the key enzyme of cholesterol synthesis. 30. Blood cholesterol level: 150-200 mg/dl. 31. 25% of cholesterol is carried on HDL and 75% is carried on LDL. 32. Esterification of cholesterol in plasma occurs by LCAT, while in tissues occurs by ACAT. 33. Factors controlling blood cholesterol level - Hereditary factors - Dietary and environmental factors - Lifestyle like smoking and coffee drinking 34. The intact sterol nucleus of cholesterol is eliminated from the body by conversion to bile acids and bile salts which are excreted in the stool. 2 35. Primary bile acids include cholic and chenodeoxycholic acid. 36. Secondary bile acids include deoxycholic and lithocholic acids 37. The key regulatory enzyme of bile acid synthesis is 7 α-hydroxylase enzyme. E. Lipid transport 38. Lipoproteins can be separated by 2 methods: ultracentrifugation and electrophoresis into: 39. The main types of plasma lipoproteins include, Chylomicrons - Very low density lipoproteins (VLDL or pre-β-lipoprotein) - Intermediate-density lipoproteins (IDL) - Low-density lipoproteins (LDL or β-lipoprotein) - High- density lipoproteins (HDL or α-lipoprotein): 40. TAG is the predominant lipid in chylomicrons and VLDL whereas cholesterol is the predominant lipid in LDL and phospholipids in HDL. 41. Functions of apolipoproteins ✓ They promote the solubility of lipids in plasma and enhance the stability of the lipoprotein particles. ✓ Act as legends for interaction with lipoprotein receptors in tissues helping to regulate tissue uptake; − Apo B-100 and apo E for the LDL receptor. − Apo E for remnant receptor. − Apo A-I for the HDL receptor. ✓ Some apolipoproteins act as enzyme activators as C-II for lipoprotein lipase and A-I for lecithin: cholesterol acyltransferase (LCAT) or enzyme inhibitors as ApoA-II and apoC-III for lipoprotein lipase, apo C-I for cholesteryl ester transfere protein. 42. The only lipoprotein that contains apo B48 is chylomicrons ✓ Function of chylomicrons is transport of dietary lipids from the intestine to the peripheral tissues 43. VLDL contains apoB100 – Its function is transport of endogenously synthesized lipids from the liver to the peripheral tissues 44. LDL (bad cholesterol) contains also apoB100 – It is the primary plasma carriers of cholesterol to the peripheral tissues. ✓ LDL concentration in blood has positive correlation with incidence of cardiovascular diseases. ✓ The LDL receptor is defective in familial hypercholesterolemia. ✓ Estrogen (female sex hormone) increase number of LDL receptors in liver. So cholesterol in females is low during reproductive period. ✓ 45. Functions of HDL:- - Removes free cholesterol from peripheral tissue to the liver (reverse cholesterol metabolism) and esterifies it using LCAT enzyme. Lecithin + cholesterol ⎯⎯⎯⎯→ Lysolecithin + cholesterol ester 3  - HDL acts as a reservoir of apo CII which is transferred to chylomicrons and VLDL to activate the lipoprotein lipase. - HDL3 in circulation, transfers some cholesterol esters to VLDL, IDL and LDL by cholesterol ester transfer protein (CETP). 46. Role of the liver in lipid transport and metabolism: 1) It facilitates the digestion and absorption of lipids by production of bile. 2) The liver has active enzyme systems for both synthesizing and oxidizing FAs. 3) It converts fatty acids to ketone bodies. 4) It plays a role in synthesis and metabolism of plasma lipoprotein 47. Fatty liver (Means chronic accumulation of TAG in the liver leading to fibrotic changes in liver cells with impaired liver function). 48. Causes of fatty liver: 1) Raised plasma levels of FFAs as in starvation, uncontrolled diabetes mellitus. 2) Metabolic block in the production of plasma lipoproteins. 3) Deficiency of choline, which is a lipotropic factor. 4) The antibiotic puromycin, carbon tetrachloride, chloroform, phosphorus, lead and arsenic. All cause fatty liver in rats. 5) Alcoholism. Reactions of lipid metabolism: 1. Activation of fatty acid to acyl CoA during fatty acid oxidation (name of the enzyme and name of the coenzyme used in this reaction) 2. Conversion of acetyl CoA to malonyl CoA during fatty acid synthesis (name of the enzyme used and name of the coenzymes) 4