Kinetic modalities of ATP synthesis. Regulation by the mitochondrial respiratory chain.
Two interconvertible kinetic modes are described for ATP synthesis by bovine heart submitochondrial particles. One mode is characterized by low apparent Km values for ADP (6-10 microM) and Pi (less than or equal to 0.25 mM), and a limited capacity for ATP synthesis (apparent Vmax approximately 500 nmol ATP.min-1.mg of protein-1). ATP synthesis occurs predominantly in this mode when the coupled activity of the respiratory chain relative to the number of functional ATP synthase complexes is low. The second kinetic mode is characterized by high apparent Km values for ADP (50-100 microM) and Pi (approximately 2.0 mM) and a high capacity for ATP synthesis (Vmax greater than 1800 nmol ATP.min-1.mg of protein-1). This mode of ATP synthesis predominates when the available free energy relative to the number of functional ATP synthase units is high. These results suggest that energy pressure in mitochondria might regulate ATP synthesis such that at low levels of energy the ATP synthase operates economically (low substrate Km values, low turnover capacity for ATP synthesis), while at high levels of energy these kinetic constraints are relaxed (high substrate Km values, high turnover capacity for ATP synthesis). The implications of these findings are discussed in relation to the cooperative-type kinetics of ATP synthesis and hydrolysis, the differential effects of a number of F0-F1 inhibitors on the rates of ATP synthesis and hydrolysis, and the controversy as to whether protonic energy in mitochondria is localized or delocalized.
D000251:Adenosine Triphosphatases / Q000037:antagonists & inhibitors; D000255:Adenosine Triphosphate / Q000096:biosynthesis*; D000818:Animals; D000900:Anti-Bacterial Agents; D002417:Cattle; D004024:Dicyclohexylcarbodiimide / Q000494:pharmacology; D006868:Hydrolysis; D007700:Kinetics; D008929:Mitochondria, Heart / Q000378:metabolism*; D009243:NAD / Q000378:metabolism; D009840:Oligomycins / Q000494:pharmacology; D010085:Oxidative Phosphorylation; D010101:Oxygen Consumption; D010455:Peptides / Q000494:pharmacology
D000900:Anti-Bacterial Agents; D009840:Oligomycins; D010455:Peptides; D009243:NAD; D004024:Dicyclohexylcarbodiimide; C012953:efrapeptin; D000255:Adenosine Triphosphate; D000251:Adenosine Triphosphatases