Dicker E, Cederbaum A I
Biochim Biophys Acta. 1985 Nov 22;843(1-2):107-13. doi: 10.1016/0304-4165(85)90056-x.
Experiments were carried out to study the effect of two commonly used glutathione-depleting agents, diethylmaleate and phorone, on the oxidation of acetaldehyde and the activity of aldehyde dehydrogenase. The oxidation of acetaldehyde by intact hepatocytes was inhibited when the cells were incubated with diethylmaleate. Washing and resuspending the cells in diethylmaleate-free medium afforded protection against the inhibition of acetaldehyde oxidation. The oxidation of acetaldehyde by isolated rat liver mitochondria as well as by disrupted mitochondria in the presence of excess NAD+ was inhibited by diethylmaleate or phorone, indicating inhibition of the low-Km aldehyde dehydrogenase. In addition, diethylmaleate inhibited oxidation of acetaldehyde by the high-Km cytosolic aldehyde dehydrogenase. Significant accumulation of acetaldehyde occurred when ethanol was oxidized by hepatocytes in the presence, but not in the absence, of diethylmaleate. Thus, diethylmaleate blocks the oxidation of added or metabolically generated acetaldehyde, analogous to results with other inhibitors of the low-Km aldehyde dehydrogenase such as cyanamide. These results suggest that caution should be used in interpreting the effects of diethylmaleate or phorone on metabolic reactions, especially those involving metabolism of aldehydes such as formaldehyde, because, in addition to depleting glutathione, these agents inhibit the low-Km aldehyde dehydrogenase.
开展实验以研究两种常用的谷胱甘肽消耗剂马来酸二乙酯和佛尔酮对乙醛氧化及乙醛脱氢酶活性的影响。当完整的肝细胞与马来酸二乙酯一起孵育时，乙醛的氧化受到抑制。将细胞洗涤并重新悬浮于不含马来酸二乙酯的培养基中可防止乙醛氧化受到抑制。马来酸二乙酯或佛尔酮可抑制分离的大鼠肝线粒体以及在过量烟酰胺腺嘌呤二核苷酸（NAD⁺）存在下破碎的线粒体对乙醛的氧化，表明低Km乙醛脱氢酶受到抑制。此外，马来酸二乙酯还抑制高Km胞质乙醛脱氢酶对乙醛的氧化。当肝细胞在有马来酸二乙酯存在而非不存在的情况下氧化乙醇时，会出现乙醛的显著积累。因此，马来酸二乙酯可阻断添加的或代谢产生的乙醛的氧化，这与其他低Km乙醛脱氢酶抑制剂（如氨甲酰）的结果类似。这些结果表明，在解释马来酸二乙酯或佛尔酮对代谢反应的影响时应谨慎，尤其是那些涉及醛（如甲醛）代谢的反应，因为除了消耗谷胱甘肽外，这些试剂还会抑制低Km乙醛脱氢酶。
