Lipids Metabolism PDF

LIPIDS METABOLISM Lipolysis & F.A oxidation Definition of lipolysis: Lipolysis is the breakdown of neutral fats into glycerol and fatty acids. Site: Lipolysis occurs most commonly in adipose tissues. Steps:  Triacylglycerols is hydrolyzed by hormone sensitive lipase (HSL)...

LIPIDS METABOLISM Lipolysis & F.A oxidation Definition of lipolysis: Lipolysis is the breakdown of neutral fats into glycerol and fatty acids. Site: Lipolysis occurs most commonly in adipose tissues. Steps:  Triacylglycerols is hydrolyzed by hormone sensitive lipase (HSL) into 2,3 diacylglycerol or 2-monoacylglycerol.  HSL attacks triacylglycerol at C1 and C3.  Additional lipases specific for monoacylglycerol remove the remaining fatty acids. Regulation: 1- Nutritional regulation: a. Over feeding of carbohydrates: Lipogenesis increased & lipolysis is inhibited b. Starvation: Low carbohydrates leading to decrease glucose uptake & oxidation which is the major source for energy. So, Lipolysis increases to give FA ready for oxidation to provide energy for the body. "When lipolysis is turned on, lipogenesis is turned off" 2- Other factors: a. Diseases: as in Diabetes mellitus, fever, infection, thyrotoxicosis, Cushing's syndrome and other stressful conditions. All these diseases are associated with increase lipolysis. b. Caffeine: increases lipolysis. Dr/ Omnia Youssef  LIPIDS METABOLISM Fatty acid Oxidatin Oxidation of FA may occur at the: β-carbon……….. The major pathway α-carbon ω-carbon Peroxisomal oxidation ……………..very long chain FA Preparatory steps before FA oxidation 1. Activation of FA: Site: The outer mitochondrial membrane. Enzyme: Acyl-CoA synthase (Thiokinase) Coenzyme: CoASH 2- Carnitine shuttle (across the inner mitochondrial membrane): Carnitine is present in all tissues & in excess in muscle. - Long chain acyl CoA will not penetrate the inner membrane of mitochondria. Dr/ Omnia Youssef  LIPIDS METABOLISM β-oxidation Site: All cells containing mitochondria. Steps: Several enzymes, known collectively as «FA oxidase» are found in the mitochondrial matrix or inner membrane adjacent to the respiratory chain. Dr/ Omnia Youssef  LIPIDS METABOLISM Energy production from complete oxidation of FA (palmitic acid): - Oxidation of FADH2 & NADH+H+ via the respiratory chain gives 5 ATPs. n - The number of turns from β-oxidation of palmitate equal to - 1 as (n= the 2 16 16 number of carbons) which equal to. Thus, - 1 = 7 turns. 2 2 Dr/ Omnia Youssef  LIPIDS METABOLISM Summary of energy yielded from complete oxidation of FA. Step Energy Fatty acid activation -2 ATP β-oxidation of palmitate 7 turns x 5 ATP = 35 ATP Oxidation of active acetate via 8 acetyl CoA x 12 ATP = 96 Krebs' cycle ATP Total energy 35 + 96 -2 = 129 α- oxidation of FA - This type of oxidation occurs at α-carbon because the β-carbon is blocked by methyl group as in oxidation of branched chain polymethyl FA (phytanic acid) - The site of oxidation is the peroxisomes ω- oxidation Site: - This is a minor pathway for FA oxidation that occurs in the endoplasmic reticulum of many tissues. - FA is oxidized to a dicarboxylic acid - The process occurs primarily with medium chain FA. Dr/ Omnia Youssef  LIPIDS METABOLISM Cholesterol Metabolism  Structure: Cholesterol is a steroid of animal tissues (animal sterol).  Source: Exogenous: from diet of animal origin (liver, meat, egg yolk & brain) Endogenous: synthesized in all nucleated cells.  Functions: 1. It is an important for cell membrane. 2. Synthesis of Steroid hormones: androgen, estrogen, progesterone & corticosteroids 3. Synthesis of vitamin D 1. Synthesis of bile acids &bile salts: It is converted into bile acids and bile salts in the liver 5. Synthesis of lipoproteins.  Synthesis of cholesterol: Site: in cytosol of all nucleated cells particularly liver, adrenal cortex, skin, testis, ovaries & brain. Precursors: Acetyl-CoA Steps: Dr/ Omnia Youssef  LIPIDS METABOLISM Regulation of cholesterol biosynthesis:  Activity of HMG-CoA reductase regulate cholesterol biosynthesis. It is under hormonal and feedback regulation in liver.  Insulin cholesterol synthesis  Glucagon cholesterol synthesis  Increase the cellular concentration of cholesterol synthesis of the enzyme HMG CoA reductase cholesterol synthesis  Inhibition by drugs (lovastatin & other statin) which is competitive inhibitor of the enzyme HMG CoA reductase cholesterol synthesis Complications of hypercholesterolemia: Increased plasma level of cholesterol predisposes to:  Atherosclerosis  Coronary heart diseases.  Hypertension (high Blood Pressure)  Stroke.  Chronic Kidney Disease  It is recommended to maintain cholesterol level < 200 mg/dL to decrease the risk of atherosclerosis and coronary heart disease. Dr/ Omnia Youssef  LIPIDS METABOLISM  Plasma cholesterol: Level: the plasma level of cholesterol is 140-200 mg/dl Factors affecting plasma cholesterol level: a) Factors increase the plasma cholesterol level: 1. Diet: high intake of carbohydrate & high intake saturated fat. 2. Diabetes mellitus. 3. Obesity. 4. Hypothyroidism (myxedema) 5. Obstructive Jaundice. b) Factors decrease the plasma cholesterol level: 1. Diet: starvation 2. Liver failure. 3. Hyperthyroidism. 4. Infection: (T.B) 5. Anemia. 6. Drugs: statins cause competitive inhibition of HMG-Co reductase. Plasma Lipids Level:  Total plasma lipids: 400-600 mg/dl  Total cholesterol: 140-200 mg/dl  Triglycerides: 40-150 mg/dl  Phospholipids: 150-200 mg/dl  Free fatty acids (FFA) (NEFA): 10-20 mg/dl Since lipids are insoluble in water, they need carriers in plasma. So, they are complexed with proteins to form lipoproteins. The protein part of lipoprotein is called apolipoprotein. Dr/ Omnia Youssef  LIPIDS METABOLISM Structure & Classification of Lipoproteins: The lipoproteins in plasma are classified into 5 major types depending on the density (by ultracentrifugation) or on the electrophoretic mobility: 1. Chylomicrons: formed in the small intestine. Contains apoprotein B-48 and TAG. 2. Very low density lipoproteins (VLDL): formed in the liver. Contain apoprotein is B-100 and TAG. 3. Intermediate density lipoproteins (IDL) 4. Low density lipoproteins (LDL): Major apoprotein in LDL is B-100. 5. High density lipoproteins (HDL): major apoprotein in HDL is apo-A.  LDL-cholesterol is deposited in tissues, so the LDL is called “bad cholesterol”. LDL concentration in blood has positive correlation with incidence of cardiovascular diseases and atherosclerosis.  The level of HDL in serum is inversely related to the incidence of myocardial infarction. As it is “antiatherogenic” or “protective” in nature, HDL is known as “good cholesterol”. Dr/ Omnia Youssef  LIPIDS METABOLISM Atherosclerosis: is a vascular disease characterized by loss of their elasticity. Factors that accelerate the process of atherosclerosis:  Obesity  Diabetes mellitus  Hypertension  Smoking  Lake of exercise  sedentary life  Stress. Dr/ Omnia Youssef