Indirect inhibition of mitochondrial dihydroorotate dehydrogenase activity by nitric oxide

被引：22

作者：

Beuneu, C

Auger, R

Löffler, M

Guissani, A

Lemaire, G

Lepoivre, M

机构：

[1] Univ Paris Sud, CNRS, UMR 8619, F-91405 Orsay, France

[2] Univ Marburg, Sch Med, Inst Physiol Chem, Marburg, Germany

[3] Inst Curie, INSERM, U350, F-91405 Orsay, France

来源：

FREE RADICAL BIOLOGY AND MEDICINE | 2000年 / 28卷 / 08期

关键词：

dihydroorotate dehydrogenase; nitric oxide; mitochondria; cytochrome c oxidase; orotate; respiration; free radicals;

D O I：

10.1016/S0891-5849(00)00239-2

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Dihydroorotate dehydrogenase (DHODH) catalyzes the oxidation of dihydroorotate to orotate in the pyrimidine biosynthesis pathway. It is functionally connected to the respiratory chain, delivering electrons to ubiquinone. We report here that inhibition of cytochrome c oxidase by nitric oxide (NO) indirectly inhibits DHODH activity. In digitonin-permeabilized cells, DEA/NO, a chemical NO donor, induced a dramatic decrease in DHO-dependent O-2 consumption. The inhibition was reversible and more pronounced at low O-2 concentration; it was correlated with a decrease in orotate synthesis. Since orotate is the precursor of all pyrimidine nucleotides, indirect inhibition of DHODH by NO may significantly contribute to NO-dependent cytotoxicity. (C) 2000 Elsevier Science Inc.

引用

页码：1206 / 1213

页数：8

共 38 条

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