Regulation of the synthesis and hydrolysis of ATP by mitochondrial ATPase. Role of Mg2+.
ATP hydrolysis, the exchange of inorganic phosphate with ATP, and ATP synthesis have been studied as a function of Mg2+ concentration in bovine heart submitochondrial particles. The rate of exchange is low at concentrations of Mg2+ below 3 mM, at higher concentrations, the exchange is several times higher. ATP hydrolysis shows a different pattern with respect to the concentration of Mg2+. The ratio of ATP hydrolyzed to ATP exchanged is above 20 at Mg2+ concentrations below 3 mM and about 5 at high Mg2+ concentrations; ADP induces a further drop of the ratio (2-3). By assays of the sensitivity of the hydrolytic reaction to organic solvents (dimethyl sulfoxide), it has been possible to determine the rate-limiting step of ATP hydrolysis. At 3 mM Mg2+, the rate-limiting step is the release of ADP in the soluble, but not in the particulate enzyme. However at higher Mg2+ concentrations, the rate-limiting step in the particulate enzyme is also ADP release. Therefore, the decrease in the ratio of ATP hydrolysis to inorganic phosphate incorporated into ATP coincides with a change in the kinetics of the enzyme, i.e. when the terminal step of ATP hydrolysis becomes rate-limiting, the inorganic phosphate-ATP exchange increases. Ca2+ induces an increase in the phosphate-ATP exchange at low Mg2+ concentrations.
D000244:Adenosine Diphosphate / Q000494:pharmacology; D000255:Adenosine Triphosphate / Q000378:metabolism*; D000266:Adenylyl Imidodiphosphate / Q000494:pharmacology; D000818:Animals; D002417:Cattle; D004121:Dimethyl Sulfoxide / Q000494:pharmacology; D007700:Kinetics; D008274:Magnesium / Q000494:pharmacology*; D008928:Mitochondria / Q000201:enzymology*; D008929:Mitochondria, Heart / Q000201:enzymology*; D006180:Proton-Translocating ATPases / Q000378:metabolism*; D013367:Submitochondrial Particles / Q000201:enzymology*
D000266:Adenylyl Imidodiphosphate; D000244:Adenosine Diphosphate; D000255:Adenosine Triphosphate; D006180:Proton-Translocating ATPases; D008274:Magnesium; D004121:Dimethyl Sulfoxide