大鼠肝脏上清液降解尿嘧啶和胸腺嘧啶的合成嘧啶抑制剂

Harold W. Barrett , S.N. Munavalli , Philip Newmark
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引用次数: 26

摘要

我们测试了一些合成嘧啶抑制大鼠组织上清液降解尿嘧啶和胸腺嘧啶的能力。在测试的9种组织中,只有肝脏制剂具有显著的嘧啶降解活性,而在测试的46种化合物中,只有胸腺嘧啶类似物5-取代尿嘧啶具有明显的嘧啶降解抑制作用。尽管它们的结构不同,但所有活性化合物都是尿嘧啶比胸腺嘧啶降解更有效的抑制剂;同样,尿嘧啶和胸腺嘧啶表现出相互抑制,但胸腺嘧啶明显更有效。结果表明,抑制作用仅发生在嘧啶降解的初始还原阶段,尿嘧啶和胸腺嘧啶的还原是由同一酶(二氢尿嘧啶脱氢酶(4,5-二氢尿嘧啶:NADP氧化还原酶,EC 1.3.1.2)催化的,抑制作用是由于底物对酶活性位点的竞争引起的。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Synthetic pyrimidines as inhibitors of uracil and thymine degradation by rat-liver supernatant

We tested the ability of a number of synthetic pyrimidines to inhibit degradation of uracil and thymine by rat-tissue supernatants. Among nine tissues tested, only liver preparations showed significant pyrimidine-degrading activity, and among 46 compounds tested, only 5-substituted uracils, analogs of thymine, showed appreciable inhibition of pyrimidine degradation. Despite their structure, all active compounds were more effective inhibitors of uracil than of thymine degradation; similarly, uracil and thymine showed reciprocal inhibition, but thymine was considerably more effective. It was concluded that inhibition occurred only during the initial reductive step in pyrimidine degradation, that reduction of both uracil and thymine was catalyzed by the same enzyme (dihydrouracil dehydrogenase (4,5-dihydrouracil: NADP oxidoreductase, EC 1.3.1.2)), and that inhibition resulted from substrate competition for the active site on the enzyme.

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