Inhibition of yeast glycolysis by nitroxyl (HNO): mechanism of HNO toxicity and implications to HNO biology.
Inhibition of yeast glycolysis by nitroxyl (HNO): mechanism of HNO toxicity and implications to HNO biology.
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DOI：
10.1016/j.abb.2005.07.012
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发表时间：
2005-10
影响因子：
3.9
通讯作者：
B. Lopez;C. E. Rodriguez;Mochtar Pribadi;N. M. Cook;M. Shinyashiki;J. Fukuto
中科院分区：
文献类型：
--
作者：
B. Lopez;C. E. Rodriguez;Mochtar Pribadi;N. M. Cook;M. Shinyashiki;J. Fukuto
研究发现硝酰基 (HNO) 可以抑制酿酒酵母中的糖酵解。 HNO 在酵母中的毒性与酵母对细胞能量糖酵解的依赖呈正相关。研究发现 HNO 能有效抑制关键的糖酵解酶 3-磷酸甘油醛脱氢酶 (GAPDH)，这种作用可能是在全细胞制剂中观察到的糖酵解抑制的原因。据推测，GAPDH 抑制是通过 HNO 与 GAPDH 活性位点硫醇残基的反应而发生的。值得注意的是，抑制 GAPDH 的 HNO 水平不会改变细胞内谷胱甘肽 (GSH) 的水平或氧化还原状态，表明 HNO 具有硫醇选择性。 HNO 在含有相对较高浓度 GSH 的细胞内环境中抑制 GAPDH 的能力是 HNO 药理学和可能的生理学的一个重要方面。
Nitroxyl (HNO) was found to inhibit glycolysis in the yeast Saccharomyces cerevisiae. The toxicity of HNO in yeast positively correlated with the dependence of yeast on glycolysis for cellular energy. HNO was found to potently inhibit the crucial glycolytic enzyme glyceraldehyde 3-phosphate dehydrogenase (GAPDH), an effect which is likely to be responsible for the observed inhibition of glycolysis in whole cell preparations. It is proposed that GAPDH inhibition occurs through reaction of HNO with the active site thiolate residue of GAPDH. Significantly, levels of HNO that inhibit GAPDH do not alter the levels or redox status of intracellular glutathione (GSH), indicating that HNO has thiol selectivity. The ability of HNO to inhibit GAPDH in an intracellular environment that contains relatively large concentrations of GSH is an important aspect of HNO pharmacology and possibly, physiology.