1. Pyruvate Oxidation: Pyruvate Dehydrogenase and the TCA Cycle

2. Aerobic “respiration” in mitochondria: important for ATP synthesis and a source of intermediates for other biochemical pathways pyruvate (C 3 H 3 O 3 ) + 4 NAD + + FAD + GDP + Pi + 2H 2 O 3 CO 2 + 4 NADH + 3 H + + FADH 2 + GTP First step: pyruvate dehydrogenase

5. Pyruvate dehydrogenase function

6. Acetyl-CoA is oxidized in the citric acid (Kreb’s, TCA) cycle

15. TCA Cycle

16. Recap TCA cycle: acetyl-CoA(C 2 H 3 O-CoA) + 3 NAD + + FAD + GDP + Pi + 2H 2 O CoA-SH + 2 CO 2 + 3 NADH + 3 H + + FADH 2 + GTP Include pyruvate oxidation: pyruvic acid(C 3 H 4 O 3 ) + 4 NAD + + FAD + GDP + Pi + 2H 2 O 3 CO 2 + 4 NADH + 4 H + + FADH 2 + GTP Complete oxidation of the pyruvate carbons Reduction of 4 NAD + and one FAD Phosphorylation of one GDP

17. The TCA cycle is a source of biosynthetic precursors But what happens when intermediates are removed from the cycle?

18. Without intermediates, the cycle stops! “Anaplerotic” reactions replenish the intermediates. Pyruvate + CO 2 + ATP + H 2 O OAA + ADP + Pi + 2 H +

19. A modification of the TCA cycle (glyoxylate cycle) lets plants and bacteria make carbohydrates from fats. isocitric lyase malate synthase to glucose

20. Summary The TCA cycle gives complete oxidation of the pyruvate carbons. And reduction of 4 NAD + and one FAD. And phosphorylation of one GDP. The TCA cycle is a source of biosynthetic precursors. Pyruvate carboxylase and the glyoxylate cycle replenish precursors Replenishment of NAD + and FAD are also essential.