MECHANISM OF ACETAMINOPHEN-STIMULATED NADPH OXIDATION CATALYZED BY THE PEROXIDASE-H2O2 SYSTEM

被引:0
作者
KELLER, RJ [1 ]
HINSON, JA [1 ]
机构
[1] UNIV ARKANSAS MED SCI HOSP,NATL CTR TOXICOL RES,DIV BIOCHEM TOXICOL,LITTLE ROCK,AR 72205
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中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
The oxidation of NADPH catalyzed by horseradish peroxidase (HRP) and hydrogen peroxide (H2O2) is markedly increased by the presence of acetaminophen in a concentration-dependent manner. The oxidation follows pseudo-first order kinetics with respect to acetaminophen concentration. The product of the oxidation is enzymatically active NADP+. The stoichiometry of the reaction shows that 1.4 mol of NADPH are oxidized per mole of H2O2 added, and the addition of superoxide dismutase to the reaction mixture increases the ratio of NADPH oxidized:H2O2 consumed, which suggests formation of superoxide as a product. Monitoring cytochrome c reduction in the presence and absence of superoxide dismutase further suggests formation of superoxide. These results indicate that the HRP-H2O2 system oxidizes acetaminophen to the phenoxyl radical, N-acetyl-p-benzosemiquinone imine, which undergoes a rapid electron transfer reaction with NADPH. The NADP thus formed reacts with molecular oxygen to produce superoxide.
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页码:184 / 187
页数:4
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