The effect of inorganic phosphate on creatine kinase in respiring rat heart mitochondria.
The ability of creatine to stimulate the respiration of rat heart mitochondria in vitro is reversibly affected by the concentration of inorganic phosphate. The rate of oxygen consumption due to post-ADP state-4 respiration in the presence of 20 mM creatine is reduced significantly when the potassium phosphate concentration is raised from 5 to 20 mM. State-3 respiration is reduced only by potassium phosphate concentrations higher than 20 mM. The rate of synthesis of creatine phosphate is also affected by phosphate concentration, and the apparent Km of the coupled reactions for ADP is significantly higher at 25 mM phosphate as compared to that at 5 mM phosphate. These observations are consistent with the hypothesis that inorganic phosphate acts as an effector molecule, regulating creatine phosphate synthesis by favoring the dissociation of mitochondrial creatine kinase from the mitochondrial membrane. Such regulation may be important in the case of cells undergoing partial or severe ischemia, where changes in phosphate concentration within this range have been reported.
D000244:Adenosine Diphosphate / Q000378:metabolism; D000818:Animals; D003402:Creatine Kinase / Q000378:metabolism*; D007700:Kinetics; D008929:Mitochondria, Heart / Q000187:drug effects / Q000201:enzymology*; D010101:Oxygen Consumption / Q000187:drug effects*; D010710:Phosphates / Q000494:pharmacology*; D051381:Rats
D010710:Phosphates; D000244:Adenosine Diphosphate; D003402:Creatine Kinase