FORMATION OF NITRIC-OXIDE BY CYTOCHROME P450-CATALYZED OXIDATION OF AROMATIC AMIDOXIMES

被引:58
作者
ANDRONIKLION, V [1 ]
BOUCHER, JL [1 ]
DELAFORGE, M [1 ]
HENRY, Y [1 ]
MANSUY, D [1 ]
机构
[1] INST CURIE,BIOL SECT,U350,F-91405 ORSAY,FRANCE
关键词
D O I
10.1016/S0006-291X(05)81006-X
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Rat liver microsomes catalyze the oxidation of para-hexyloxybenzamidoxime 1 to the corresponding arylamide 2 and NO2 -, by NADPH and O2. Involvement of cytochromes P450 as catalysts of this reaction was shown by the strong inhibitory effects of CO and miconazole and the spectacular increase of the activity upon treatment of rats with dexamethasone, a specific inducer of cytochromes P450 of the 3A subfamily. Formation of NO during oxidation of I was shown by detection of the formation of cytochrome P450- and cytochrome P420-Fe(II)-NO complexes by visible and EPR spectroscopy. The formation of these complexes should be responsible, at least in part, for the fast decrease of the rate of microsomal oxidation of 1 with time. These results suggest that exogenous compounds containing amidine or amidoxime functions could act as precursors of NO in vivo after in situ oxidation by cytochromes P450. © 1992 Academic Press, Inc.
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页码:452 / 458
页数:7
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