Exploring sites on mitochondrial ATPase for catalysis, regulation, and inhibition.
Evidence is presented that mitochondrial ATPase has two types of sites that bind adenine nucleotides. The catalytic site, C, binds the substrates ATP, GTP, or ITP and the inhibitor guanylyl imidodiphosphate (GMP-PNP). A second type of site, R, binds ATP, ADP, adenylyl imidodiphosphate (AMP-PNP), and the chromium complexes of ATP or ADP. All of these substances binding to the R site inhibit the hydrolysis of ATP in a competitive manner; their inhibition of hydrolysis of ITP and GTP is noncompetitive. GMP-PNP inhibits oxidative phosphorylation in submitochondrial particles but AMP-PNP does not. The localization on mitochondrial membranes of sites for the binding of various antibiotics that inhibit oxidative phosphorylation is discussed.
D000244:Adenosine Diphosphate / Q000494:pharmacology; D000251:Adenosine Triphosphatases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D000255:Adenosine Triphosphate / Q000096:biosynthesis / Q000378:metabolism / Q000494:pharmacology; D000266:Adenylyl Imidodiphosphate / Q000494:pharmacology; D000818:Animals; D000900:Anti-Bacterial Agents / Q000378:metabolism; D001665:Binding Sites; D001667:Binding, Competitive; D002384:Catalysis; D002417:Cattle; D002857:Chromium / Q000494:pharmacology; D006150:Guanine Nucleotides / Q000494:pharmacology; D006160:Guanosine Triphosphate / Q000378:metabolism; D007292:Inosine Nucleotides / Q000378:metabolism; D007700:Kinetics; D008930:Mitochondria, Liver / Q000201:enzymology*; D008931:Mitochondria, Muscle / Q000201:enzymology*; D010085:Oxidative Phosphorylation / Q000187:drug effects; D051381:Rats
D000900:Anti-Bacterial Agents; D006150:Guanine Nucleotides; D007292:Inosine Nucleotides; D002857:Chromium; D000266:Adenylyl Imidodiphosphate; D000244:Adenosine Diphosphate; D006160:Guanosine Triphosphate; D000255:Adenosine Triphosphate; D000251:Adenosine Triphosphatases