Dicker E, Cederbaum A I
Arch Biochem Biophys. 1984 Oct;234(1):187-96. doi: 10.1016/0003-9861(84)90340-0.
Crotonaldehyde was oxidized by disrupted rat liver mitochondrial fractions or by intact mitochondria at rates that were only 10 to 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 mitochondria, and by isolated hepatocytes. Inhibition by crotonaldehyde was competitive with respect to acetaldehyde, and the Ki for crotonaldehyde was about 5 to 20 microM. 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 to 40% inhibition of formaldehyde oxidation, which was similar to the inhibition produced by cyanamide. This suggested that 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.
巴豆醛可被破碎的大鼠肝线粒体组分或完整线粒体氧化，但其氧化速率仅为乙醛氧化速率的10%至15%。尽管巴豆醛是一种较差的氧化底物，但它是线粒体醛脱氢酶、完整线粒体和分离的肝细胞氧化乙醛的有效抑制剂。巴豆醛的抑制作用对乙醛具有竞争性，巴豆醛的Ki约为5至20微摩尔。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的乙醛水平非常低。巴豆醛使乙醛的积累增加了10倍以上，这表明巴豆醛除了抑制添加的乙醛氧化外，还抑制了乙醇代谢产生的乙醛的氧化。甲醛是低Km线粒体醛脱氢酶以及胞质谷胱甘肽依赖性甲醛脱氢酶的底物。巴豆醛是甲醛线粒体氧化的有效抑制剂，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%至40%的抑制作用，这与氨甲酰类似物产生的抑制作用相似。这表明部分甲醛氧化是通过线粒体醛脱氢酶进行的，部分是通过甲醛脱氢酶进行的。巴豆醛的抑制作用具有竞争性这一事实可能具有价值，因为其他常用的醛脱氢酶抑制剂是该酶的不可逆抑制剂。
