Oxidative Phosphorylation Notes

ATP synthase, a protein complex, links electron transport and ATP synthesis.
ATP synthase spans the inner mitochondrial membrane and protrudes into the matrix.
The proton motive force interacts with the F0 portion of ATP synthase.
F0 functions as an ion channel, allowing protons to flow along their gradient back into the matrix.
Chemiosmotic coupling harnesses the chemical energy of the gradient to phosphorylate ADP, forming ATP.
The ETC generates a high concentration of protons in the intermembrane space.
Protons flow through the F0 ion channel of ATP synthase back into the matrix.
The F1 portion of ATP synthase uses the energy released from the electrochemical gradient to phosphorylate ADP to ATP.
The specific mechanism of ADP phosphorylation is still debated.

Chemiosmotic coupling describes a direct relationship between the proton gradient and ATP synthesis.
This is the predominant mechanism accepted in the scientific community.
Conformational coupling suggests an indirect relationship between the proton gradient and ATP synthesis.
ATP is released by the synthase due to conformational change caused by the gradient.
The F1 portion of ATP synthase acts like a turbine spinning within a stationary compartment to harness gradient energy for chemical bonding.

When the proton motive force is dissipated through the F0 portion of ATP synthase, the free energy change $\triangle G = -220 \text{ kJ/mol}$ , which is highly exergonic.
Phosphorylating ADP to form ATP is an endergonic process.
The energy harnessed from the exergonic reaction drives the endergonic reaction.

Oxidative phosphorylation and the citric acid cycle are closely coordinated.
O2 and ADP are key regulators of oxidative phosphorylation.
If O2 is limited, the rate of oxidative phosphorylation decreases, and the concentrations of NADH and FADH2 increase.
The accumulation of NADH inhibits the citric acid cycle.
This coordinated regulation is known as respiratory control.
In the presence of adequate O2, the rate of oxidative phosphorylation depends on the availability of ADP.
ADP and ATP concentrations are reciprocally related.
ADP accumulation signals the need for ATP synthesis.
ADP allosterically activates isocitrate dehydrogenase, increasing the rate of the citric acid cycle and the production of NADH and FADH2.
Elevated levels of these reduced coenzymes increase the rate of electron transport and ATP synthesis.

The citric acid cycle and oxidative phosphorylation occur in the mitochondria.
In the mitochondrial matrix, the citric acid cycle completely oxidizes acetyl CoA to carbon dioxide.
Energy is conserved via the formation of high-energy electron carriers such as FADH2 and NADH.
ATP is also indirectly formed via GTP synthesis.
These electron-rich carriers transfer their electrons to the electron transport chain, located along the inner mitochondrial membrane.
A series of oxidation-reduction reactions occur in specific complexes until oxygen, the final electron acceptor, is reduced and forms H2O.
This electron pathway generates an electrochemical proton gradient harnessed by ATP synthase to generate ATP.

Control of the citric acid cycle is NADH-dependent.
When NADH accumulates, isocitrate dehydrogenase inhibition occurs, stopping both the citric acid cycle and the electron transport chain.
Glycolysis and fatty acids are major sources of acetyl CoA for the citric acid cycle.