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.

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