Mitochondrion, Electron Transport, and ATP Synthesis

Outer Mitochondrial Membrane: Permeable to small molecules and ions.
Inner Mitochondrial Membrane: Contains proteins for the electron transport chain (ETC) and ATP synthesis.
Intermembrane Space: Area between the inner and outer membranes; high concentration of H+ ions generated during electron transport.
Matrix: Enclosed by the inner membrane; contains enzymes for Krebs cycle, mitochondrial DNA, and ribosomes.

Proton Concentration:
- High [H+] in the intermembrane space leads to low pH.
- Low [H+] in the matrix leads to high pH.
Proton-Motive Force:
- Created by the active transport of protons across the inner mitochondrial membrane during electron transfer.
- Used to drive ATP synthesis.

Electron Transport:
- Involves transfer of electrons from NADH and FADH2 through a series of proteins.
- Generates a proton gradient across the inner mitochondrial membrane.
ATP Synthesis:
- Driven by the proton gradient through ATP synthase (Complex V).
- The energy from the potential difference is used to convert ADP + Pi into ATP.

Glycolysis:
- Breakdown of glucose into pyruvate, producing NADH and ATP.
Acetyl-CoA Production:
- Pyruvate is converted to Acetyl-CoA by the pyruvate dehydrogenase complex, releasing CO2.
Krebs Cycle:
- Acetyl-CoA is oxidized to CO2, generating NADH and FADH2, which feed into the ETC.
Electron Transfer and Oxidative Phosphorylation:
- NADH and FADH2 donate electrons to the ETC.
- Oxidative phosphorylation couples electron transport to ATP synthesis by creating a proton gradient.

Components of ETC:
- Composed of four major complexes (I - IV) and mobile electron carriers (coenzyme Q and cytochrome c).
- Each complex contains prosthetic groups that facilitate electron transfer.
Electron Flow:
- Electrons move through carriers in order of increasing standard reduction potential (E°’).
- Oxygen is the final electron acceptor, forming water.

Complex I (NADH Dehydrogenase):
- Accepts electrons from NADH and transfers them to ubiquinone (Q), pumping protons into the intermembrane space (4 H+).
Complex II (Succinate Dehydrogenase):
- Accepts electrons from succinate (TCA intermediate) and transfers them to Q without pumping protons.
Complex III (Cytochrome bc1):
- Transfers electrons from QH2 to cytochrome c, pumping 4 H+ across the membrane.
Complex IV (Cytochrome c Oxidase):
- Uses electrons from cytochrome c to reduce O2, pumping 2 additional H+.

Structure:
- Composed of two functional units: Fo (membrane-integrated proton channel) and F1 (catalytic site for ATP synthesis).
Mechanism of Action:
- Protons flow through Fo, causing rotation of the C subunits, which drives conformational changes in F1 to synthesize ATP from ADP and Pi.

Proton Pumping Efficiency:
- Approximately 10 protons are pumped per NADH, producing about 2.5 ATP.
- Approximately 6 protons per FADH2, yielding approximately 1.5 ATP.
- Requires 3 protons to synthesize 1 ATP.

ETC Inhibitors:
- Certain chemicals (e.g., rotenone, antimycin A, cyanide) can inhibit specific complexes, preventing ATP synthesis.
Uncoupling Agents:
- Compounds like DNP can dissipate the proton gradient, decoupling electron transport from ATP synthesis, resulting in heat production rather than ATP.

Role of Uncoupling in Brown Fat:
- In hibernating animals and infants, the uncoupling protein (thermogenin) allows for heat generation instead of ATP production, helping to maintain body temperature during cold exposure.