Dirty Medicine Biochemistry Series: Oxidative Phosphorylation

Overview

• Oxidative phosphorylation is also known as the electron transport chain (ETC).
• Involves the transformation of glucose to pyruvate, then to acetyl-CoA, which enters the TCA (Krebs) cycle, generating NADH and FADH2.
• These molecules play crucial roles in oxidative phosphorylation, facilitating ATP production.

Key Concepts

• Objective: Couple energy stored in electron acceptors to a proton gradient that drives ATP synthesis.
• Components:
  • Inner mitochondrial membrane: houses ETC components.
  • Mitochondrial matrix and intermembrane space: proton gradient forms here.

Electron Transport Chain Design

• Complexes:
  • Complex 1 (blue)
  • Complex 2 (light pink)
  • Complex 3 (light green)
  • Complex 4 (peach)
  • Complex 5 (ATP synthase, gray triangle)
• Molecules:
  • Coenzyme Q (CoQ)
  • Cytochrome C

Process

• Electron Shuffling:
  • NADH donates electrons to Complex 1, supercharging it, allowing proton pumping.
  • FADH2 donates electrons to Complex 2; cannot pump protons.
  • CoQ acts as a common electron acceptor from Complex 1 and 2.
  • Electrons move from CoQ to Complex 3, supercharging it for proton pumping.
  • Cytochrome C transfers electrons to Complex 4, which pumps more protons.
  • Final electron acceptor: Oxygen, forming water.
• Proton Gradient: Protons accumulate in the intermembrane space, creating an electrochemical gradient.

ATP Synthesis

• ATP Synthase (Complex 5):
  • Utilizes the proton gradient to convert ADP to ATP.
  • Protons flow down the gradient through ATP synthase, providing energy for ATP formation.

Inhibitors

• Complex Inhibitors:
  • Rotanone: Complex 1
  • Antimycin: Complex 3
  • Cyanide/Carbon monoxide: Complex 4/Cytochrome C
  • Oligomycin: ATP synthase
  • 2,4-DNP: Uncouples proton gradient

ATP Production

• Glycolysis:
  • Net 2 ATP, plus NADH contributing 3-5 ATP.
• Pyruvate Metabolism:
  • NADH contributes 5 ATP.
• TCA Cycle:
  • Net 2 ATP.
  • NADH and FADH2 contribute significantly to ATP production via ETC.

Yield

• For each NADH, 2.5 ATP; for each FADH2, 1.5 ATP.
• Total ATP from glycolysis to ETC: 30-32 ATP.

Conclusion

• Oxidative phosphorylation, a crucial step in energy production, generates the most ATP due to NADH and FADH2 utilized in the electron transport chain.