Department of Food and Nutrition, College of Life Science and Nano Technology, Hannam University, 461-6 Jeonmin-dong, Yuseong-gu, Daejeon 305-811, Korea.
Nutr Res Pract. 2008 Winter;2(4):195-9. doi: 10.4162/nrp.2008.2.4.195. Epub 2008 Dec 31.
Alcoholism has been associated with folate deficiency in humans and laboratory animals. Previous study showed that ethanol feeding reduces the dehydrogenase and hydrolase activity of 10-formyltetrahydrofolate dehydrogenase (FDH) in rat liver. Hepatic ethanol metabolism generates acetaldehyde and acetate. The mechanisms by which ethanol and its metabolites produce toxicity within the liver cells are unknown. We purified FDH from rat liver and investigated the effect of ethanol, acetaldehyde and acetate on the enzyme in vitro. Hepatic FDH activity was not reduced by ethanol or acetate directly. However, acetaldehyde was observed to reduce the dehydrogenase activity of FDH in a dose- and time-dependent manner with an apparent IC(50) of 4 mM, while the hydrolase activity of FDH was not affected by acetaldehyde in vitro. These results suggest that the inhibition of hepatic FDH dehydrogenase activity induced by acetadehyde may play a role in ethanol toxicity.
酗酒与人类和实验动物的叶酸缺乏有关。先前的研究表明,乙醇喂养会降低大鼠肝脏中 10-甲酰四氢叶酸脱氢酶(FDH)的脱氢酶和水解酶活性。肝内乙醇代谢生成乙醛和乙酸。乙醇及其代谢物在肝细胞内产生毒性的机制尚不清楚。我们从大鼠肝脏中纯化了 FDH,并研究了乙醇、乙醛和乙酸在体外对该酶的影响。乙醇或乙酸本身并不直接降低肝 FDH 活性。然而,观察到乙醛以剂量和时间依赖的方式降低 FDH 的脱氢酶活性,其表观 IC(50)为 4mM,而 FDH 的水解酶活性在体外不受乙醛影响。这些结果表明,乙醛诱导的肝 FDH 脱氢酶活性抑制可能在乙醇毒性中起作用。