Kreb Cycle 2014_15

Kreb Cycle Overview

  • Known as the Citric Acid Cycle or Tricarboxylic Acid Cycle (TCA).

  • Series of oxidative reactions that occur in the mitochondrial matrix.

  • Used by all aerobic organisms to produce energy, specifically ATP.

  • Involves oxidation of acetate (as Acetyl-CoA) derived from carbohydrates, fats, and proteins.

  • Produces CO2 and ATP while transferring reducing equivalents to NAD+ or ubiquinone for the respiratory chain.

  • Provides precursors for certain amino acids and produces NADH.

Stages of the Kreb Cycle

Stage 1: Glycolysis and Production of Acetyl-CoA

  • Glycolysis converts glucose into pyruvate.

  • Pyruvate Dehydrogenase Complex converts pyruvate into Acetyl-CoA, releasing CO2 and producing NADH.

  • Acetyl-CoA enters the Kreb Cycle.

Stage 2: Citric Acid Cycle

  • Acetyl-CoA is oxidized to Citrate and then to Oxaloacetate.

  • Produces additional CO2, NADH, FADH2, and includes various steps:

    • Citrate synthase condenses Acetyl-CoA and oxaloacetate to form citrate.

    • Aconitase converts citrate to isocitrate then regenerates oxaloacetate.

    • Key reactions involve decarboxylation and reduction, generating NADH and FADH2.

  • End product: Regeneration of Oxaloacetate allows cycle continuation.

Stage 3: Electron Transfer and Oxidative Phosphorylation

  • Reduced electron carriers (NADH, FADH2) transfer electrons to the electron transport chain.

  • Oxidative phosphorylation generates ATP through creation of a proton motive force across the inner mitochondrial membrane.

  • Oxygen acts as the final electron acceptor, producing H2O.

Functions of the Kreb Cycle

  • Extracts maximum electrons from Acetyl CoA to drive proton pumping in the electron transport chain.

  • Intermediary metabolism involving various substrates: NAD+, oxaloacetate, Acetyl-CoA, ADP.

Key Enzymes and Reactions

Pyruvate Dehydrogenase Complex

  • Converts pyruvate into Acetyl-CoA.

  • Involves oxidative decarboxylation, producing NADH and releasing CO2.

Specific Steps of the Kreb Cycle

  • Step 1: Citrate Synthase catalyzes the condensation of Acetyl-CoA and oxaloacetate into citrate.

  • Step 3: Isocitrate Dehydrogenase catalyzes oxidative decarboxylation, producing NADH.

  • Step 4: Formation of Succinyl-CoA from a-ketoglutarate occurs alongside NADH formation.

  • Step 5: Succinyl-CoA synthetase catalyzes substrate-level phosphorylation to produce GTP or ATP.

  • Step 6: Succinate Dehydrogenase converts succinate into fumarate, producing FADH2.

  • Step 8: Final conversion of Malate to Oxaloacetate, generating NADH.

Catabolism Pathways

  • Breakdown of major food groups leads to acetyl CoA:

    • Carbohydrates: Glycogenolysis > Glycolysis > Pyruvate > Acetyl-CoA.

    • Lipids: Lipolysis to free fatty acids > β-Oxidation > Acetyl-CoA.

    • Proteins: Proteolysis and deamination > carbon skeleton to Acetyl-CoA.

Regulation of the Kreb Cycle

  • Controlled by substrate availability: concentrations of NAD+, oxaloacetate, Acetyl-CoA, ADP influence enzyme activities.