Citric Acid Cycle and Oxidative Phosphorylation

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Citric Acid Cycle / Krebs cycle / TCA:

• Occurs in mitochondria.

• Will not occur anaerobically.

• Primary function: oxidation of acetyl-CoA to CO2; produces NADH, FADN2, and GTP.

• All enzymes located in mitochondria except succinate dehydrogenase, which is in inner membrane.

Citric Acid Cycle Control:

• NADH and ATP: inhibit isocitrate dehydrogenase.

• ADP: activates isocitrate dehydrogenase.

• Thiamine, lipolic acid, CoA, FAD, NAD: activate alpha-ketoglutarate dehydrogenase.

• Substrate level phosphorylation of GDP to GTP: succinyl-CoA synthetase.

• Citrate synthase forms citrate.

Citric Acid Cycle Intermediate Usage:

• Citrate: fatty acid synthesis.

• Succinyl-CoA: heme synthesis and ketone body activation.

• Malate: gluconeogenesis.

Electron Transport Chain Reactions:

• NADH to NAD.

• FADH2 to FAD.

NADH and FADH:

• NADH comes from Citric Acid Cycle and pyruvate dehydrogenase.

• FADH2 comes from succinate dehydrogenase in Citric Acid Cycle.

Mitochondrial Electron Transport Chain:

• Works like a battery.

• Location 1: oxidative reaction releases electrons at high energy (NADH).

• Location 2: an electron acceptor awaits to be reduced (NADH dehydrogenase; complex I).

• Current flows from 1 to 2; a machinery is placed in between and work is done - ATP is produced.

Oxidative Phosphorylation:

• ATP synthesis.

• Carried out by F0F1 ATP synthase complex in inner membrane of mitochondria.

Tissue Hypoxia:

• Decreased ETC causing decreased ATP production.

• Glycolysis increases causing lactic acidosis.

Electron Transport Chain Inhibitors:

• CN (irreversible binding to cytochrome a/a3 preventing e transfer).

• CO (binding to cytochrome a/a3).

Electron Transport Chain Uncouplers:

• Decrease proton gradient.

• Decreased ATP.

Reactive Oxygen Species:

• Partially reduced O2 produces reactive oxygen species like superoxide, hydrogen peroxide, hydroxyl radical.

• PMNs use oxygen radicals to kill bacteria.

• Reactive oxygen species accumulation causes damage to tissues.

• Defenses include: superoxide dismutase and catalase.

Additional Citric Acid Cycle Notes:

• Number of ATP molecules produced in TCA cycle: 24.

• Citrate synthase inhibited by: NADH.

• Total ATP from 1 molecule of acetyl CoA: 12.

• Succinate dehydrogenase blocked by: malonate.

• Diabetic ketoacidosis: lack of oxaloacetate to allow acetyl CoA to enter Citric Acid Cycle.

Additional Readings:

Basic Biochemistry

1. Nucleic Acid Structure and Organization
2. DNA Replication and Repair
3. Transcription and RNA Processing
4. Genetic Code, Mutations, and Translation
5. Genetic Regulation
6. Recombinant DNA
7. Amino Acids, Proteins, Enzymes
8. Hormones
9. Vitamins
10. Energy Metabolism
11. Glycolysis and Pyruvate Dehydrogenase
12. Citric Acid Cycle and Oxidative Phosphorylation
13. Glycogen, Gluconeogenesis, and Hexose Monophosphate Shunt
14. Lipid Synthesis and Storage
15. Lipid Mobilization and Catabolism
16. Amino Acid Metabolism Disorders
17. Purine and Pyrimidine Metabolism
18. Electron Transport
19. Citric Acid Cycle and Glyoxylate Cycle
20. Glycolysis
21. Pyruvate Metabolism
22. Mitochondrial ATP formation
23. Gluconeogenesis
24. Glycogen Metabolism
25. Nitrogen Fixation (Metabolism) reactions, and Heme Metabolism
26. Amino Acid Metabolism
27. What is Medium Chain Acyl-CoA Dehydrogenase Deficiency (MCADD)?

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