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Introduction of Glucose Metabolism Lecture-3 Fate of Pyruvate & Citric Acid Cycle Fate of pyruvate 1- Lactate (in cytosol) Enzyme: lactate dehyrogenase (LDH) in anaerobic glycolysis 2- Acetyl CoA in mitochondria Enzyme: pyruvate dehydrogenase occurs in aerobic glycolysis Acetyl CoA is required for citric acid cycle (CAC) 3- Oxalacetate in mitochondria Enzyme: pyruvate carboxylase Oxalacetate is required for: 1- Citric acid cycle (condenses with acetyl CoA): to yield energy ATP OR 2-Gluconeogenesis (to synthesize glucose) Fate of Pyruvate Glucose glycolysis Gluconeogenesis mitochondria OXALACETATE No Oxygen No Mitochondria OR BOTH PYRUVATE Oxygen & Mitochondria ACETYL CoA CITRIC ACID CYCLE LACTATE Formation of acetyl CoA from pyruvate • Pyruvate (end product of aerobic glycolysis) is transported into the mitochondria. • In the mitochondrial matrix, pyruvate is converted to acetyl CoA by pyruvate dehydrogenase complex (multienzyme 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 pyruphosphate, TPP (derived from thiamine, vitamin B1) 2- NAD+ (derived from niacin) 3- FAD (derived from riboflavin) 4- Lipoic acid 5- Coenzyme A (derived from pantothenic acid) Pyruvate dehydrogenase complex PYRUVATE ACETYL CoA Citric acid cycle or,(Krebs cycle) Citric Acid Cycle Citric acid cycle is the final pathway where the oxidative metabolism of Carbohydrates (as glucose), proteins (amino acids) & lipids (fatty acids) to yield energy (ATP) 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) 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) Net = 12 ATP / one acetyl CoA Citric Acid Cycle CYCLE - SUMMARY Acetyl CoA 3 NAD 3 NADH + H 2 CO2 1 FAD 1 FADH2 1 ADP 1 ATP Citric acid cycle or,(Krebs cycle)