U01.01.094 Electron transport chain and oxidative phosphorylation

The electron transport chain (ETC) and oxidative phosphorylation are critical metabolic processes responsible for ATP production in mitochondria. This process involves the transfer of electrons from NADH and FADH2 through various protein complexes, ultimately leading to the creation of a proton gradient that drives ATP synthesis.

Key Steps in Electron Transport Chain and Oxidative Phosphorylation:

Electron Transport Chain:
- NADH electrons enter the mitochondria via the malate-aspartate or glycerol-3-phosphate shuttle.
- Electrons from FADH2 are transferred to Complex II (succinate dehydrogenase), but at a lower energy level than NADH.
- Electrons pass through complexes I, II, III, and IV, generating a proton gradient across the inner mitochondrial membrane.
Proton Gradient & ATP Production:
- The proton gradient created by electron transport powers ATP synthase, which synthesizes ATP from ADP and inorganic phosphate (Pi).

Overview of the Key Components and Inhibitors:

Component	Function	Inhibitors
Complex I (NADH dehydrogenase)	Accepts electrons from NADH and transfers them to CoQ	Rotenone (blocks NADH entry)
Complex II (Succinate dehydrogenase)	Accepts electrons from FADH2 and transfers them to CoQ	No specific inhibitors listed
Complex III (Cytochrome bc1)	Transfers electrons from CoQ to cytochrome c	Antimycin A (blocks electron transfer)
Complex IV (Cytochrome c oxidase)	Accepts electrons from cytochrome c and transfers them to oxygen to form water	Azide, Cyanide, Carbon monoxide (inhibit oxygen binding)
ATP Synthase (Complex V)	Synthesizes ATP from ADP and Pi, powered by the proton gradient	Oligomycin (inhibits ATP production)

ATP Yield from NADH and FADH2:

NADH: Each NADH produces 2.5 ATP.
FADH2: Each FADH2 produces 1.5 ATP.

Poisons and Inhibitors of the Electron Transport Chain

Electron Transport Inhibitors:
- Rotenone: Inhibits Complex I.
- Antimycin A: Inhibits Complex III.
- Cyanide, Azide, Carbon Monoxide: Inhibit Complex IV, blocking electron transfer to oxygen.
ATP Synthase Inhibitors:
- Oligomycin: Inhibits ATP synthase, preventing ATP production despite a proton gradient.
Uncoupling Agents:
- These agents disrupt the proton gradient, reducing ATP synthesis but allowing electron transport to continue. They generate heat due to the energy released as protons move back into the mitochondrial matrix without driving ATP synthesis.
- Examples:
  - 2,4-Dinitrophenol: Often used illicitly for weight loss.
  - Aspirin overdose: Causes fever due to uncoupling.
  - Thermogenin: Found in brown adipose tissue, which is rich in mitochondria.

Points to Remember:

The electron transport chain is critical for ATP production, powered by the electron transfer from NADH and FADH2.
Inhibitors of the electron transport chain, such as cyanide and rotenone, block the production of ATP.
ATP production is highly dependent on the proton gradient created by the electron transport chain.
Uncoupling agents disrupt this gradient, halting ATP production but increasing oxygen consumption and heat generation.

Summary:

Understanding the function of the electron transport chain and the effects of various inhibitors is essential for USMLE Step 1. Be sure to memorize the inhibitors and their respective complexes, as well as the role of the proton gradient in driving ATP synthesis.

Your voice matters – comment below!Cancel reply

This site uses Akismet to reduce spam. Learn how your comment data is processed.

USMLE Step 1 Review Series

Curriculum