| The oldest and simplest known mechanism of respiratory control is accomplished by the supply of ADP. This is based on the fact that when added to isolated mitochondria, it stimulates respiration and ATP synthesis. When ADP is completely converted to ATP, respiration returns to the initial rate. Oxidative phosphorylation is tightly coupled to fundamental pathways such as glycolysis, fatty acid oxidation and the TCA cycle through feedback regulatory mechanisms. The ratios of NADH/NAD and ATP/ADP feedback on key enzymes, such as PFK-1, pyruvate dehydrogenase and isocitrate dehydrogenase. If, for example, oxidative phosphorylation is switched off because of high ATP, both NADH and ATP will negatively feedback on other energy-producing pathways. Since oxidative phosphorylation responds to the supply of FADH2, NADH, ADP, and Pi as well as the ATP/ADP ratio, magnitude of the membrane potential, uncoupling and hormonal factors, its modes of regulation are clearly more complex than was once thought.
|
