INHIBITION OF THE OXIDATION OF ACETALDEHYDE AND FORMALDEHYDE BY HEPATOCYTES AND MITOCHONDRIA BY CROTONALDEHYDE
INHIBITION OF THE OXIDATION OF ACETALDEHYDE AND FORMALDEHYDE BY HEPATOCYTES AND MITOCHONDRIA BY CROTONALDEHYDE
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DOI：
10.1016/0003-9861(84)90340-0
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发表时间：
1984-01-01
影响因子：
3.9
通讯作者：
CEDERBAUM, AI
中科院分区：
文献类型：
--
作者：
DICKER, E;CEDERBAUM, AI
巴豆醛被破坏的大鼠肝线粒体组分或完整的线粒体氧化的速率仅为乙醛的10 - 15%。虽然巴豆醛是一种不良的氧化底物，但它是线粒体醛脱氢酶、完整线粒体和分离肝细胞对乙醛氧化的有效抑制剂。巴豆醛的抑制作用相对于乙醛是竞争性的，巴豆醛的Ki约为5 - 20 μ M。巴豆醛对谷氨酸或琥珀酸的氧化没有影响。在乙醇代谢过程中检测到非常低水平的乙醛。巴豆醛使乙醛的积累增加超过10倍，表明巴豆醛除了抑制添加的乙醛的氧化外，还抑制由乙醇代谢产生的乙醛的氧化。甲醛是低Km线粒体醛脱氢酶的底物，也是细胞溶质谷胱甘肽依赖性甲醛脱氢酶的底物。巴豆醛是一种有效的甲醛氧化的抑制剂，但对甲醛脱氢酶的活性没有影响。在肝细胞中，巴豆醛对甲醛氧化产生约30 - 40%的抑制作用，这与氰胺产生的抑制作用相似。显然，部分甲醛氧化通过线粒体醛脱氢酶发生，部分通过甲醛脱氢酶发生。巴豆醛的抑制是竞争性的，这一事实可能是有价值的，因为其他常用的醛脱氢酶抑制剂是该酶的不可逆抑制剂。
Crotonaldehyde was oxidized by disrupted rat liver mitochondrial fractions or by intact mitochondria at rates that were only 10-15% that of acetaldehyde. Although a poor substrate for oxidation, crotonaldehyde is an effective inhibitor of the oxidation of acetaldehyde by mitochondrial aldehyde dehydrogenase, by intact mitchondria and by isolated hepatocytes. Inhibition by crotonaldehyde was competitive with respect to acetaldehyde, and the Ki for crotonaldehyde was about 5-20 .mu.M. Crotonaldehyde had no effect on the oxidation of glutamate or succinate. Very low levels of acetaldehyde were detected during the metabolism of ethanol. Crotonaldehyde increased the accumulation of acetaldehyde more than 10-fold, indicating that crotonaldehyde, besides inhibiting the oxidation of added acetaldehyde, also inhibited the oxidation of acetaldehyde generated by the metabolism of ethanol. Formaldehyde was a substrate for the low-Km mitochondrial aldehyde dehydrogenase, as well as for a cytosolic, glutathione-dependent formaldehyde dehydrogenase. Crotonaldehyde was a potent inhibitor of mitochondrial oxidation of formaldehyde, but had no effect on the activity of formaldehyde dehydrogenase. In hepatocytes, crotonaldehyde produced about 30-40% inhibition of formaldehyde oxidation, which was similar to the inhibition produced by cyanamide. Evidently part of the formaldehyde oxidation occurred via the mitochondrial aldehyde dehydrogenase, and part via formaldehyde dehydrogenase. The fact that inhibition by crotonaldehyde is competitive may be of value since other commonly used inhibitors of aldehyde dehydrogenase are irreversible inhibitors of the enzyme.