The reduction of 6-N-hydroxylaminopurine to adenine by xanthine oxidase.
The genotoxic and mutagenic compound 6-N-hydroxylaminopurine (HAP) can be detoxified in vitro by enzymatic N-reduction to adenine. This reaction is catalysed by both rat and rabbit liver cytosolic fractions. The formation of adenine was monitored using HPLC. Subcellular distribution of the activity, kinetic parameters and the influence of various cofactors and inhibitors were determined. The N-reduction required NADH or hypoxanthine or xanthine and was strongly inhibited by allopurinol. These observations suggested that the N-reductase activity is due to xanthine oxidase (EC 1.2.3.2). Moreover, the involvement of xanthine oxidase is supported by the observation that purified cow milk xanthine oxidase also catalysed this reaction. The N-reduction of HAP was inhibited only weakly by oxygen. In addition, the formation of adenine is catalysed by either the oxidase or dehydrogenase form of xanthine oxidase. Thus, this reaction should be significant for the in vivo detoxification of HAP.
Clement
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Pharmazeutisches Institut, Christian-Albrechts Universität, Kiel, Federal Republic of Germany.
Kunze
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T
D000225:Adenine / Q000031:analogs & derivatives* / Q000378:metabolism*; D000818:Animals; D002021:Buffers; D003600:Cytosol / Q000378:metabolism; D005260:Female; D006863:Hydrogen-Ion Concentration; D008658:Inactivation, Metabolic; D007700:Kinetics; D008099:Liver / Q000378:metabolism*; D008297:Male; D010084:Oxidation-Reduction; D011817:Rabbits; D051381:Rats; D017208:Rats, Wistar; D014968:Xanthine Dehydrogenase / Q000378:metabolism; D014969:Xanthine Oxidase / Q000037:antagonists & inhibitors / Q000378:metabolism*
D002021:Buffers; C032610:6-N-hydroxylaminopurine; D014968:Xanthine Dehydrogenase; D014969:Xanthine Oxidase; D000225:Adenine