大鼠心脏中黄嘌呤的三种形式：受体氧化还原酶

Three forms of xanthine: acceptor oxidoreductase in rat heart.

作者信息

Kaminski Z W, Pohorecki R, Ballast C L, Domino E F

出版信息

Circ Res. 1986 Dec;59(6):628-32. doi: 10.1161/01.res.59.6.628.

DOI:10.1161/01.res.59.6.628

Abstract

The enzyme xanthine: acceptor oxidoreductase found in rat heart equilibrates between three forms differing in electron acceptor specificity. Form D transfers electrons exclusively to NAD+ and accounts for 85% of total oxidoreductase activity. Form O transfers electrons to molecular oxygen and accounts for 8%. The D/O form prefers NAD+, but without NAD+ transfers electrons to oxygen. Interconversion from D to O and O to D forms is catalyzed by sulfhydryl group-modifying reagents: Cd2+, Cu2+, disulfiram, and heating with dithiothreitol. This suggests that sulfhydryl groups participate in the first stage of enzyme conversion. The NADH/NAD+ concentration ratio may regulate the dehydrogenase activity of xanthine:acceptor oxidoreductase (NAD+-dependent activity of D and D/O forms). Accumulating NADH inhibits hypoxanthine hydroxylation. The amount of form O increases during cardiac ischemia, facilitating superoxide radical-ion generation. Also, NADH/NAD+ does not regulate form O, promoting adenylate nucleotide pool depletion, especially in the heart which has low de novo purine nucleotide synthesis.

摘要

在大鼠心脏中发现的黄嘌呤

受体氧化还原酶可在三种电子受体特异性不同的形式之间达到平衡。D型仅将电子转移给NAD⁺，占总氧化还原酶活性的85%。O型将电子转移给分子氧，占8%。D/O型优先选择NAD⁺，但在没有NAD⁺时会将电子转移给氧。巯基修饰试剂（Cd²⁺、Cu²⁺、双硫仑）以及与二硫苏糖醇一起加热可催化D型与O型之间的相互转化。这表明巯基参与了酶转化的第一阶段。NADH/NAD⁺浓度比可能调节黄嘌呤：受体氧化还原酶的脱氢酶活性（D型和D/O型的NAD⁺依赖性活性）。积累的NADH会抑制次黄嘌呤羟基化。在心脏缺血期间，O型的量会增加，这有利于超氧阴离子自由基的产生。此外，NADH/NAD⁺不调节O型，会促进腺苷酸核苷酸池的消耗，尤其是在从头嘌呤核苷酸合成较低的心脏中。