尿酸对黄嘌呤氧化酶的抑制作用及其对超氧阴离子生成的影响。

Inhibition of xanthine oxidase by uric acid and its influence on superoxide radical production.

作者信息

Radi R, Tan S, Prodanov E, Evans R A, Parks D A

机构信息

Department of Biochemistry, Faculty of Medicine, University of the Republic, Montevideo, Uruguay.

出版信息

Biochim Biophys Acta. 1992 Jul 31;1122(2):178-82. doi: 10.1016/0167-4838(92)90321-4.

DOI:10.1016/0167-4838(92)90321-4

PMID:1322703

Abstract

The inhibition of xanthine oxidase by its reaction product, uric acid, was studied by steady state kinetic analysis. Uric acid behaved as an uncompetitive inhibitor of xanthine oxidase with respect to the reducing substrate, xanthine. Under 50 microM xanthine and 210 microM oxygen, the apparent K(i) for uric acid was 70 microM. Uric acid-mediated xanthine oxidase inhibition also caused an increase in the percentage of univalent reoxidation of the enzyme (superoxide radical production). Steady-state rate equations derived by the King-Altman method support the formation of an abortive-inhibitory enzyme-uric acid complex (dead-end product inhibition). Alternatively, inhibition could also depend on the reversibility of the classical ping-pong mechanism present in xanthine oxidase-catalyzed reactions.

摘要

通过稳态动力学分析研究了尿酸（黄嘌呤氧化酶的反应产物）对黄嘌呤氧化酶的抑制作用。就还原底物黄嘌呤而言，尿酸表现为黄嘌呤氧化酶的非竞争性抑制剂。在50微摩尔的黄嘌呤和210微摩尔的氧气条件下，尿酸的表观抑制常数（K(i)）为70微摩尔。尿酸介导的黄嘌呤氧化酶抑制作用还导致该酶单电子再氧化百分比（超氧阴离子生成）增加。用金-奥特曼方法推导的稳态速率方程支持形成一种无效抑制性酶-尿酸复合物（终产物抑制）。另外，抑制作用也可能取决于黄嘌呤氧化酶催化反应中存在的经典乒乓机制的可逆性。