Glucose Metabolism Lecture 3 PDF

Introduction of Glucose Metabolism Lecture-3 FATES OF PYRUVATE & CITRIC ACID CYCLE  FATES OF PYRUVATE Acetyl CoA ( in mitochondria): Enzyme: pyruvate 1- dehydrogenase complex, Acetyl CoA is required for citric acid cycle (CAC) 2- Lactate (in cytosol) : Enzyme: lactate dehydr...

Introduction of Glucose Metabolism Lecture-3 FATES OF PYRUVATE & CITRIC ACID CYCLE  FATES OF PYRUVATE Acetyl CoA ( in mitochondria): Enzyme: pyruvate 1- dehydrogenase complex, Acetyl CoA is required for citric acid cycle (CAC) 2- Lactate (in cytosol) : Enzyme: lactate dehydrogenase (LDH) in anaerobic glycolysis 3- Oxalacetate ( in mitochondria): Enzyme: pyruvate carboxylase Oxalacetate is required for Gluconeogenesis 4- Alanine. (in cytosol) Enzyme: Alanine transaminase (ALT) FORMATION OF ACETYL COA FROM PYRUVATE In the mitochondrial matrix, pyruvate is converted to acetyl CoA by pyruvate dehydrogenase complex This reaction is irreversible Pyruvate dehydrogenase complex is composed of three enzymes & five coenzymes Coenzymes of the complex are derived from water soluble vitamins: 1- Thiamine pyrophosphate, TPP (derived from thiamine, vitamin B1) 2- Lipoic acid 3- Coenzyme A (derived from pantothenic acid B5) 4- FAD (derived from riboflavin B2) 5- NAD+ (derived from niacin B3) Pyruvate dehydrogenase complex deficiency is one of the most common neurodegenerative disorders associated with congenital lactic acidosis (cause too much lactic acid to build up in the body from pyruvate) CITRIC ACID CYCLE OR,(KREBS CYCLE) TCA Citric acid cycle : is the final pathway for CHO , Lipid , protein catabolism. (stage 3) Acetyl CoA is the end product for oxidation of carbohydrates, lipids & proteins Acetyl CoA condenses with oxalacetate to form citrate (first reaction of the cycle) Energy production by the TCA cycle 3 NADH are produced = 3 X 3 = 9 ATP (by oxidative phosphorylation) One FADH2 is produced = 1 X 2 = 2 ATP (by oxidative phosphorylation) One ATP is produced (by substrate level phosphorylation) The rat poison fluoroacetate reacts with OAA to form fluorocitrate that inhibits aconitase, result in convulsions, cardiac arrhythmias, and death.  Regulation of the TCA cycle The TCA cycle is regulated by the cell’s need for energy in the form of ATP. 1. When ADP levels are high relative to ATP, that is, when the cell needs energy , the TCA cycle speeds up. 2. When the concentration of ATP is high, the cell has an adequate energy supply, the TCA cycle is inhibited. Regulatory enzymes of Kreb’s: 1- Citrate synthase 2- Isocitrate dehydrogenase 3- Alpha keto glutarate  Functions of TCA cycle 1- Final pathway for complete oxidation of all food- stuffs (carbohydrate, lipids, proteins) which are converted to acetyl CoA. 2- 1 Major source of energy for cells except RBCs 3- Major source of succinyl CoA , which used for  Hb synthesis  ketone bodies activation  detoxication by conjugation