Citric Acid Cycle and Related Pathways Summary

Respiration

  • Conversion of nutrients (carbohydrates, proteins, fats) into useful energy for the cell.

Citric Acid Cycle

  • Also known as the Krebs cycle.

  • Occurs in the mitochondrial matrix (except succinate dehydrogenase, which is in the inner mitochondrial membrane).

  • Each cycle produces 3 NADH, 1 FADH2, and 1 GTP. Input is 2 Carbons (1 Acetyl CoA) and releases 2 CO2CO_2 molecules.

Pyruvate Dehydrogenase (PD)

  • A large multimeric complex with three subunits: E1, E2, E3.

  • E1 subunit: Pyruvate → Acetaldehyde → Acetyl-CoA + CO2CO_2.

  • PD Kinase: Puts phosphate on PD → Inactivates.

  • PD Phosphatase: Takes phosphate off → Activates.

Lipoamide

  • Functions as an electron carrier within the PD complex.

  • Exists in oxidized (S-S) and reduced (SH SH) forms.

Citric Acid Cycle Intermediates

  • Citrate: Glyoxylate cycle, allosteric effector, shuttle system.

  • a-Ketoglutarate: Amino acid/nitrogen metabolism.

  • Succinyl-CoA: Heme synthesis, amino acid metabolism.

  • Succinate: Glyoxylate metabolism, odd chain fatty acid metabolism.

  • Fumarate: Nucleotide metabolism.

  • Malate: Shuttle system.

  • Oxaloacetate: Gluconeogenesis, amino acid metabolism.

Key Steps in the Citric Acid Cycle

  • Citrate Synthase: Oxaloacetate + Acetyl-CoA → Citrate.

  • Isocitrate Dehydrogenase: Isocitrate + NAD+NAD^+ → a-ketoglutarate + NADHNADH + CO2CO_2 (First oxidative decarboxylation).

  • a-ketoglutarate Dehydrogenase: a-ketoglutarate + NAD+NAD^+ + CoA-SH → Succinyl-CoA + NADHNADH + CO2CO_2 (Second oxidative decarboxylation).

  • Succinyl-CoA Synthetase: Succinyl-CoA + GDP + Pi → Succinate + GTP + CoA-SH (Only Substrate Level Phosphorylation in Cycle).

  • Succinate Dehydrogenase: Succinate + FAD → Fumarate + FADH2FADH_2 (Third Oxidation of Cycle).

  • Fumarase: Fumarate + H2OH_2O → L-Malate.

  • Malate Dehydrogenase: Malate + NAD+NAD^+ → Oxaloacetate + NADHNADH (Fourth and final oxidation of cycle).

Glyoxylate Cycle

  • Bypasses the two decarboxylation steps of the citric acid cycle.

  • Net Synthesis of Glucose from Acetyl-CoA.

  • Input 4 Carbons (2-Acetyl CoA). Releases 0 CO2CO_2 Molecules.

  • Produces One Extra Oxaloacetate.

  • Two Oxidations: 1 NADH, 1 FADH2FADH_2.

Reactions

  • Isocitrate Lyase: Isocitrate → Succinate + Glyoxylate.

  • Malate Synthase: Acetyl-CoA + Glyoxylate → L-Malate.

Ketone Body Metabolism

  • Occurs in mitochondria.

  • Involves the conversion of acetyl-CoA to acetoacetate, D-B-hydroxybutyrate, and acetone.