Participation of N1-oxide derivatives of adenine nucleotides in the phosphotransferase activity of liver mitochondria.
The modified adenine nucleotides ATP-NO, ADP-NO, and AMP-NO were tested as potential substrates and/or inhibitors of mitochondrial phosphotransferases. ADP-NO is not recognized by the translocase system located in the inner mitochondrial membrane; however, it is rapidly phosphorylated to ATP-NO in the outer compartment of mitochondria, by way of the nucleosidediphosphate kinase (EC 2.7.4.6) reaction, provided there is sufficient ATP in the mitochondria. AMP-NO is not phosphorylated by liver mitochondria to the corresponding nucleoside diphosphate; it cannot serve as substrate for adenylate kinase (EC 2.7.4.3). ATP-NO and ADP-NO, however, are substrates of this enzyme. The apparent equilibrium constant for the reaction, ADP-NO + ADP right harpoon over left harpoon ATP-NO + AMP, of 0.908 at pH 7.4 and 5 mM Mg(2+) is significantly higher than that of the reaction with natural nucleotides. Although adenosine N(1)-oxide is easily phosphorylated to AMP-NO by adenosine kinase [Schnebli et al. (1967) J. Biol. Chem. 242, 1997-2004], the formation of corresponding nucleoside triphosphate in vivo seems also to be limited by adenylate kinase; adenosine N(1)-oxide cannot replace adenosine in restoring the normal ATP level in ethionine-treated rats.
D000227:Adenine Nucleotides / Q000378:metabolism*; D000244:Adenosine Diphosphate / Q000031:analogs & derivatives / Q000378:metabolism; D000255:Adenosine Triphosphate / Q000031:analogs & derivatives / Q000378:metabolism; D000818:Animals; D002250:Carbon Radioisotopes; D006593:Hexokinase / Q000378:metabolism; D066298:In Vitro Techniques; D007700:Kinetics; D051379:Mice; D008930:Mitochondria, Liver / Q000201:enzymology*; D010085:Oxidative Phosphorylation; D010087:Oxides; D010770:Phosphotransferases / Q000378:metabolism*; D011770:Pyruvate Kinase / Q000378:metabolism; D051381:Rats
D000227:Adenine Nucleotides; D002250:Carbon Radioisotopes; D010087:Oxides; D000244:Adenosine Diphosphate; D000255:Adenosine Triphosphate; D010770:Phosphotransferases; D006593:Hexokinase; D011770:Pyruvate Kinase