Keller R J, Hinson J A
Department of Pharmacology, University of Arkansas for Medical Sciences, Little Rock 72205.
Drug Metab Dispos. 1991 Jan-Feb;19(1):184-7.
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 imime, which undergoes a rapid electron transfer reaction with NADPH. The NADP thus formed reacts with molecular oxygen to produce superoxide.
辣根过氧化物酶（HRP）和过氧化氢（H₂O₂）催化的NADPH氧化反应，在对乙酰氨基酚存在时会以浓度依赖的方式显著增加。该氧化反应相对于对乙酰氨基酚浓度遵循准一级动力学。氧化产物是具有酶活性的NADP⁺。反应的化学计量表明，每加入1摩尔H₂O₂会氧化1.4摩尔NADPH，向反应混合物中添加超氧化物歧化酶会增加氧化的NADPH与消耗的H₂O₂的比例，这表明超氧化物是产物之一。在有和没有超氧化物歧化酶的情况下监测细胞色素c的还原情况，进一步表明会形成超氧化物。这些结果表明，HRP - H₂O₂系统将对乙酰氨基酚氧化为苯氧自由基，即N - 乙酰 - 对 - 苯半醌亚胺，它与NADPH发生快速电子转移反应。由此形成的NADP与分子氧反应生成超氧化物。
