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KREB CYCLE OR CITRIC ACID CYCLE OR TRICARBOXYLIC ACID CYCLE (TCA) . Involves oxidation of acetyl CoA to CO2 AND H2O. 65-70 percentage ATP synthesized . Final common oxidative pathway for carbohydrates, fats and amino acid. Connecting all individual metabolic pathways. Important metabolic pathway for energy supply to body. Cyclic process. Oxaloacetate is considered to play catalytic role . CIRIC ACID ENZYMES ARE FOUND IN MITOCHONDRIAL MATRIX Substrate have to flow across the outer and inner part of mitochondria. PRODUCTION OF ACETYL Co-A Pyruvate dehydrogenase complex: it is multienzyme containing 3 enzymes associated together non-covalently. E-1:Pyruvate dehydrogenase E-2:Dihydrolipoyl transacetylase E-3:Dihydrolipoyl dehydrogenase REACTIONS OF CITRIC CYCLE: 8 reactions citrate synthase Aconitase Iso-citrate dehydrogenase a ketoglutarate dehydrogenase Succinyl- CoenzymeA synthetase Succinate dehyrogenase Fumerase Malate dehydrogenase . CONDENSATION . Involves condensation of acetyl-CoA with oxaloacetate , catalyzed by citrate synthase. DEHYDRATION HYDRATION OXIDATIVE DECARBOXYLATION . • Involves oxidation of Isocitrate to a- ketoglutarate. . OXIDATIVE DECARBOXYLATION • Involves oxidation of a-ketoglutarate to Succinyl-CoA. SUBSTRATE LEVEL PHOSPHORYLATION . HYDRATION . DEHYDROGENATION REGULATION Brought either by enzymes or level of ADP. 3 Enzymes regulated TCA:1. citrate synthase: inhibited by ATP , NAD, acetyl CoA and succinyl CoA. 2. Isocitrate dehydrogenase: activated by ADP and inhibited by ATP and NADH. 3. alfa-ketoglutarate dehydrogenase: inhibited by succinyl CoA and NADH. 4. Availability of ADP Amphibolic nature Kreb cycle is both catabolic and anabolic in nature. Hence regarded as Amphibolic. Involved in gluconeogenesis , transamination and deamination. Also provide precursors for many biosynthetic pathway. For ex. 1. alfa-ketoglutarate and oxaloacetate : serve as precursor of amino acids, aspartate and glutamate by simple transamination and required for synthesis of non-essential amino acids ,purines and pyrimidines. 2. succinyl CoA : used for synthesis of heme. Anaplerotic reactions The reactions concerned to fill up the intermediates of citric acid cycle are Anaplerotic reactions or anaplerosis. - 1.Pyruvate + HCO3 + ATP pyruvate carboxylase oxaloacetate +ADP+ Pi pyruvate carboxylase : catalyses conversion of pyruvate to oxaloacetate . take place in mammalian kidney and liver. 2. PEP + CO2 + GDP PEP carboxykinase oxaloacetate + GTP take place in heart and skeletal muscle. - 3. PEP + HCO3 PEP carboxylase oxaloacetate + Pi take place in higher plants , yeast and bacteria. - 4. Pyruvate + HCO3 + NAD(P)H malic enzyme malate + NAD(P)+ widely distributed in eukaryotes and prokaryotes. GLYOXYLATE CYCLE Plants and many organisms are equipped with glyoxylate cycle- to convert fat into carbohydrates. oThe animals like man cannot carry out the net synthesis of carbohydrates from fat. oActive in the germinating seeds of some plants . o take place in glyoxysomes which is specialized cellular organelles where fatty . acid synthesis is operative. o oEach turn of this cycle consumes 2 molecules of acetyl-CoA and produces one molecule of succinate. REGULATION OF GLYOXYLATE AND CITRIC ACID CYCLE THANK YOU