Metabolism and Energy Production Overview

Introduction to Metabolism

  • Pyruvate dehydrogenase converts pyruvate to acetyl-CoA under aerobic conditions.

Acetyl-CoA in the TCA Cycle

  • Acetyl-CoA is oxidized in the TCA cycle, generating reduced electron carriers for ATP synthesis.
    • 1 NADH ~ 2.5 ATP
    • 1 QH2 (FADH2) ~ 1.5 ATP
  • Each TCA cycle round produces 3 NADH, 1 QH2, and 1 GTP (ATP).

Overview of the Citric Acid Cycle (TCA Cycle)

  • Also known as the tricarboxylic acid cycle or Krebs Cycle.
  • Acetyl-CoA condenses with oxaloacetate, resulting in citrate and the loss of 2 CO2.
  • Key steps: 5 critical steps focused on energy extraction and CO2 release during the cycle.

Mitochondrial Compartmentalization

  • Glycolysis occurs in the cytoplasm; the TCA cycle occurs in mitochondria.
  • Mitochondria share a common ancestor with certain bacteria, evidenced by their DNA and ribosomes.

Key Steps of the Citric Acid Cycle

  1. Acetyl-CoA Entry: Acetyl-CoA enters the cycle involving energy input but no energy extraction.
  2. First Decarboxylation: Isocitrate oxidized to α-ketoglutarate, generating NADH and releasing CO2.
  3. Second Decarboxylation: α-Ketoglutarate to succinyl-CoA, producing NADH and releasing CO2.
  4. Substrate Level Phosphorylation: Succinyl-CoA produces GTP (or ATP)
  5. Oxidations: Succinate to fumarate and malate back to oxaloacetate, generating QH2 and NADH, respectively.

Regulation of the TCA Cycle

  • Three irreversible steps are key regulatory points.

Electron Transport Chain (ETC)

  • Occurs in the inner mitochondrial membrane with four protein complexes.
    • Protons are pumped into the intermembrane space, creating a gradient that drives ATP synthesis.

Complexes of the ETC

  1. Complex I: Transfers electrons from NADH to ubiquinone (Q).
  2. Complex II: Produces QH2 from succinate.
  3. Complex III: Transfers electrons from QH2 to cytochrome c.
  4. Complex IV: Reduces O2 to water, also pumping protons.

ATP Synthase Function

  • Uses the proton gradient to synthesize ATP from ADP+Pi. It operates through a rotary mechanism involving conformational changes in subunits.

Thermogenin and Heat Production

  • Uncoupling protein allowing proton return, generating heat instead of ATP, plays a role in brown fat metabolism.

Malate-Aspartate Shuttle

  • Transfers electrons from cytosolic NADH to mitochondrial NADH for ATP generation (~2.5 ATP).
  • Different systems in muscle yield ~1.5 ATP per cytosolic NADH.