Lecture 3 (01/14)

Overview of Reactions in the TCA Cycle

Reaction 5 and 6: Overview

  • Conversion of Succinate to Fumarate

    • Succinate is converted to fumarate by the enzyme succinate dehydrogenase.

    • The reaction releases hydrogen and reduces NAD+ to NADH.

    • Oxidation occurs at the carbon atom due to bond changes.

Reaction 8: Formation of Malate

  • Uses malate dehydrogenase to convert fumarate to malate.

  • The reaction is energetically unfavorable but occurs due to low concentration of oxaloacetate, which drives the reverse reaction.

    • This allows for continuous operation of the TCA cycle.

Energy Yield and Processes

  • Key Outputs from the TCA Cycle

    • 3 NADH, 2 CO2, 1 GTP, and 1 FADH2 produced per cycle.

    • One molecule of oxaloacetate is used initially, with regeneration occurring to maintain the cycle.

    • The process is crucial for converting acetyl CoA to CO2, releasing energy stored in these molecules.

Regulation of the TCA Cycle

Overview of Regulation

  • Green elements indicate activation, while red indicates inhibition within the metabolic pathway.

Key Enzymes and Their Regulation

  • Pyruvate Dehydrogenase

    • A multimeric enzyme likely regulated allosterically.

  • Citrate Synthase

    • Inhibited by ATP and NADH, activated by ADP.

  • Isocitrate Dehydrogenase

    • Similar activation and inhibition patterns as citrate synthase.

Anaplerotic Reactions

  • Defined as reactions that replenish TCA cycle intermediates.

  • Pyruvate Carboxylase Reaction

    • Converts pyruvate to oxaloacetate.

    • Primarily occurs in the direction toward oxaloacetate production.

  • PEP Carboxylase Reaction

    • Converts phosphoenolpyruvate (PEP) to oxaloacetate (unidirectional).

  • Malate Formation

    • Converts pyruvate to malate, reversing the original pathway.

Mechanisms Involving Pyruvate Carboxylase

  • Catalytic Sites

    • Active sites indicated: Catalytic site 1 (blue) and site 2 (yellow).

    • First catalytic site activates bicarbonate with ATP involvement.

    • The product is influenced by CO2, playing a vital role in later reactions.

Summary of Conversions and Energy Changes

  • When succinate converts to fumarate, one FADH2 is produced.

  • Transition from malate to oxaloacetate completes the cycle and maintains energy flow.