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. 1974 Nov;71(11):4630–4634. doi: 10.1073/pnas.71.11.4630

Participation of N1-Oxide derivatives of Adenine Nucleotides in the Phosphotransferase Activity of Liver Mitochondria

G Jebeleanu 1, N G Ty 1, H H Mantsch *, O Bârzu 1, G Niac †, I Abrudan 1
PMCID: PMC433942  PMID: 4373722

Abstract

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 ⇌ ATP-NO + AMP, of 0.908 at pH 7.4 and 5 mM Mg2+ is significantly higher than that of the reaction with natural nucleotides.

Although adenosine N1-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 N1-oxide cannot replace adenosine in restoring the normal ATP level in ethionine-treated rats.

Keywords: oxidative phosphorylation, adenine nucleotide N1-oxides, substrate specificity, in vivo phosphorylation

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Selected References

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