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KREBS CYCLE. Introduction Let us review fates of Pyruvate Depending on the oxidation state of the cell: Aerobic – converted to acetyl-CoA via TCA cycle.

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Presentation on theme: "KREBS CYCLE. Introduction Let us review fates of Pyruvate Depending on the oxidation state of the cell: Aerobic – converted to acetyl-CoA via TCA cycle."— Presentation transcript:

1 KREBS CYCLE

2 Introduction Let us review fates of Pyruvate Depending on the oxidation state of the cell: Aerobic – converted to acetyl-CoA via TCA cycle Anaerobic – converted to lactate (lactate dehydrogenase ) Pyruvate also is converted to : Alanine Oxaloacetate Glucose [Gluco- neogenesis] to alcohol (yeasts)

3 Importance of conversion of pyruvate into acetyl-CoA Pyruvate formed in Cytosol(Cytoplasmic solution) is transferred to mitochondrion by a transport protein to be converted to acetyl-CoA by oxidative decarboxylation. Catalyzed by a multi enzyme complex called as pyruvate dehydrogenase enzyme complex [PDH). This conversion is of Central Importance in Metabolism----Why?????

4 Concerted Reaction

5 Sources and fates of Acetyl Co-A 5

6 TCA or Tricarboxylic Acid Cycle [also known as Kreb’s or Citric Acid cycle] Definition: The metabolic pathway in which Acetyl-coA A is oxidized to carbon dioxide and water and leads to formation of ATP, NADH and FADH2. TCA cycle is a common pathway for oxidation of all nutrients (carbohydrate, lipids and proteins). Location : The cycle operates in mitochondrial matrix in close proximity to electron transport chain which is present in the inner mitochondrial membrane.

7 TCA Cycle Reactions

8 Products of one turn of the citric acid cycle. At each turn of the cycle, three NADH, one FADH2, one GTP (or ATP), and two CO2 are released. (2 carbons)

9 Oxidative decarboxylation of the two pyruvates gives 2 NADH + that gives  6 ATP.Oxidation of isocitrate by isocitrate dehydrogenase gives 2NADH + that gives  6 ATP.Oxidative decarboxylation of  -ketoglutarate to succinyl-CoA gives--- 2 NADH + that gives  6 ATP.Substrate level phosphorylation from succinyl-CoA gives  2 ATP.Oxidation of succinate to fumarate gives 2 FADH2, thus  4 ATP.Oxidation of malate to oxaloacetate gives 2 NADH +,  6 ATP Thus, for each mole of glucose 30 ATP are produced. Complete oxidation of one glucose molecule under aerobic conditions gives 8 ATP at aerobic glycolysis + 30 ATP at Krebs' cycle ---------giving a total of 38 ATP Bioenergetics of Kreb’s cycle:

10 Generation of ATP in Catabolism of Glucose

11 Amphibolic nature of TCA cycle Involved in gluconeogenesis, Transamination and Deamination. Oxaloacetae and α - ketoglutarate ---precursors for Asp and Glu which in turn are precursors for other amino acids, purines and pyrimidines. Succinyl Co-A –used for synthesis of porphyrins and heme. Mitochondrial Citrate is transported to cytosol where it is cleaved to provide acetyl Co-A for synthesis of fatty acids, sterols etc,

12 Importance of Krebs' cycle Energy production: Oxidation acetyl- CoA into CO 2 + H 2 O with generation of energy. (30ATP from one glucose molecule in TCA). It is a major source of succinyl-CoA which is used for: Synthesis of hemoglobin and other porphyrins Ketolysis: For activation of ketone bodies Detoxication by conjugation. It provides intermediates for synthesis of amino acids e.g.  -Ketoglutarate can give rise to glutamic acid by transamination. Oxaloacetate can give rise to asparatic acid by transamination.

13 THANKYOU


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