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Stages of Metabolism

Stages of Metabolism. Pyruvate Oxidation. Conversion to acetyl–CoA Catalyzed by pyruvate dehydrogenase Decarboxylation - gives CO 2 and aldehyde (uses thiamine pyrophosphate ) Oxidation - gives acetyl group (uses FAD and NAD + , makes NADH) Transfer to CoASH (uses lipoic acid ).

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Stages of Metabolism

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  1. Stages of Metabolism

  2. Pyruvate Oxidation • Conversion to acetyl–CoA • Catalyzed by pyruvate dehydrogenase • Decarboxylation - gives CO2 and aldehyde (uses thiamine pyrophosphate) • Oxidation - gives acetyl group (uses FAD and NAD+, makes NADH) • Transfer to CoASH (uses lipoic acid)

  3. Citric Acid Cycle Overview In the citric acid cycle, • Acetyl (2C) bonds to oxaloacetate (4C) to form citrate (6C). • Oxidation and decarboxylation reactions convert citrate to oxaloacetate. • Oxaloacetate bonds with another acetyl to repeat the cycle.

  4. Citric Acid Cycle The citric acid cycle(stage 3) • Operates under aerobic conditions only. • Oxidizes the two-carbon acetyl group in acetyl CoA to 2CO2. • Produces reduced coenzymes NADH and FADH2 and one ATP directly.

  5. Citric Acid CycleEntry from Acetyl–CoA

  6. Citric Acid CycleCitrate to Isocitrate

  7. Citric Acid CycleFirst Oxidation Key point: requires NAD+

  8. Citric Acid CycleSecond Oxidation Key point: requires NAD+

  9. Citric Acid CycleSubstrate-Level Phosphorylation

  10. Citric Acid CycleThird Oxidation

  11. Citric Acid CycleHydration

  12. Citric Acid CycleFourth Oxidation Key point: requires NAD+

  13. An acetyl group bonds with oxaloacetate to form citrate Two decarboxylations remove two carbons as 2CO2 Four oxidations provide hydrogen for 3NADH and one FADH2. A direct phosphorylation forms GTP (ATP).

  14. acetyl-SCoA + 3NAD++ FAD + GDP+Pi+ 2H2O 2CO2 + 3NADH+ 3H++ FADH2 + HS-CoA + GTP One turn of the citric acid cycle produces: 2 CO2 1 GTP (1ATP) 3 NADH 1 HS-COA 1 FADH2 Overall Chemical Reaction for the Citric Acid Cycle

  15. o Conversion of 3 alcohol into 2 o alcohol: Now able to be oxidized Citric Acid Cycle

  16. Regulation of Citric Acid Cycle The reaction rate for the citric acid cycle Increases when high levels of ADP or NAD+ activate isocitrate dehydrogenase and -ketoglutarate dehydrogenase Decreases when high levels of ATP or NADH inhibit isocitrate dehydrogenase. Decreases when high levels of NADH or succinyl–CoA inhibit -ketoglutarate dehydrogenase. Formation of acetyl–CoA from pyruvate (catalyzed by pyruvate dehydrogenase) also activated by ADP and inhibited by ATP and NADH.

  17. Mitochondrial Structure

  18. FMN (Flavin mononucleotide) FMN coenzyme • Contains flavin, ribitol,and phosphate. • Accepts 2H+ + 2e- to form reduced coenzyme FMNH2.

  19. Coenzyme Q (Q or CoQ) Coenzyme Q (Q or CoQ)is • A mobile electron carrier derived from quinone. • Reduced when the keto groups accept 2H+ and 2e-

  20. Cytochromes Cytochromes (cyt)are • Proteins containing heme groups with iron ions. Fe3+ + 1e- Fe2+ • Abbreviated as cyt a, cyt a3, cyt b, cyt c, and cyt c1.

  21. 2 NADH + 2 H+ + O2 2 NAD+ + 2 H2O 2 FADH2 + O2 2 FAD + 2 H2O Electron Transport Chain Cyt c1

  22. Chemiosmotic Model of Electron Transport During electron flow Complexes I, III, and IV pump protons into the intermembrane space creating a proton gradient. Protons pass through ATP synthase to return to the matrix. The flow of protons through ATP synthase provides the energy for ATP synthesis (oxidative phosphorylation).

  23. ATP Synthase InATP synthase • Protons flow back to the matrix through a channel in the F0 complex. • Proton flow provides the energy that drives ATP synthesis by the F1 complex

  24. From NADH (Complex I) provides sufficient energy for 3ATPs NADH + 3ADP + 3PiNAD+ + 3ATP From FADH2 (Complex II) provides sufficient energy for 2ATPs FADH2 + 2ADP + 3PiFAD + 2ATP ATP from Electron Transport

  25. Regulation of Electron Transport The electron transport system is regulated by High levels of ADP and NADH that activate electron transport. Low levels of ADP, Pi, oxygen, and NADH that decrease electron transport activity.

  26. Summary: C6H12O6 2 pyruvate + 2H2O + 6 ATP glucose ATP from Glycolysis Reaction Pathway ATP for One Glucose ATP from Glycolysis Activation of glucose -2 ATP Oxidation of 2 NADH (as FADH2) 4 ATP Direct ADP phosphorylation (two triose) 4 ATP 6 ATP

  27. Summary: 2 Pyruvate 2 Acetyl CoA + 6 ATP ATP from Two Pyruvates Under aerobic conditions • 2 pyruvate are oxidized to 2 acetyl CoA and 2 NADH. • 2 NADH enter electron transport to provide 6 ATP.

  28. Summary: 2Acetyl CoA + 24 ADP + 24 Pi 4CO2 + 2H2O + 24 ATP + 2 CoASH ATP from Citric Acid Cycle Reaction Pathway ATP (One Glucose) ATP from Citric Acid Cycle (2 acetyl-CoA) Oxidation of 2 isocitrate (2NADH) 6 ATP Oxidation of 2 -ketoglutarate (2NADH) 6 ATP 2 Direct substrate phosphorylations (2GTP) 2 ATP Oxidation of 2 succinate (2FADH2) 4 ATP Oxidation of 2 malate (2NADH) 6 ATP 24 ATP

  29. Overall ATP Production for one glucose • C6H12O6 + 6O2 + (36 – 38)ADP + (36 – 38) Pi • glucose6CO2 + 6H2O +(36 – 38) ATP ATP from Glucose One glucose molecule undergoing complete oxidation provides: From glycolysis 6 – 8 ATP From 2 pyruvate 6 ATP From 2 acetyl CoA 24 ATP 36-38 ATP

  30. ATP Energy from Glucose The complete oxidation of glucose yields • 6 CO2 • 6 H2O • 36-38 ATP

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