Bradford B U, Handler J A, Seed C B, Forman D T, Thurman R G
Department of Pharmacology, University of North Carolina, Chapel Hill 27599-7365.
Arch Biochem Biophys. 1991 Aug 1;288(2):435-9. doi: 10.1016/0003-9861(91)90217-7.
The purpose of this work was to compare the roles of a newly described mitochondrial dehydrogenase and catalase in ethanol elimination in deer mice deficient in alcohol dehydrogenase (ADH-). Fructose was used because of its well-known ability to stimulate dehydrogenase-dependent ethanol metabolism. Rates of ethanol metabolism in vivo were decreased significantly by about 60% in a dose-dependent manner by fructose in deer mice fed an ethanol-containing or a corn oil control diet. In addition, rates of metabolism of methanol, a selective substrate for catalase in rodents, were similar to rates of ethanol elimination and were decreased from 6.9 +/- 1.0 to 1.7 +/- 0.5 mmol/kg/h by fructose, supporting the hypothesis that catalase and not a mitochondrial dehydrogenase predominates in ethanol oxidation in ADH-deer mice. Glycolate, a substrate for peroxisomal H2O2 generation, reversed the inhibition of alcohol metabolism by fructose completely, indicating that fructose did not inhibit catalase directly. As expected, the ATP/ADP ratio was decreased by fructose significantly from 4.2 +/- 0.4 to 2.4 +/- 0.4 in deer mouse livers. These data are consistent with the hypothesis that fructose decreases catalase-dependent ethanol metabolism in vivo by inhibiting hepatic H2O2 generation.
这项工作的目的是比较一种新描述的线粒体脱氢酶和过氧化氢酶在缺乏乙醇脱氢酶（ADH-）的鹿鼠体内乙醇消除过程中的作用。使用果糖是因为其具有刺激依赖脱氢酶的乙醇代谢的众所周知的能力。在喂食含乙醇或玉米油对照饮食的鹿鼠中，果糖以剂量依赖性方式使体内乙醇代谢率显著降低约60%。此外，甲醇是啮齿动物中过氧化氢酶的选择性底物，其代谢率与乙醇消除率相似，果糖使其从6.9±1.0降至1.7±0.5 mmol/kg/h，这支持了在ADH-鹿鼠体内，过氧化氢酶而非线粒体脱氢酶在乙醇氧化中起主要作用的假说。乙醇酸是过氧化物酶体产生H2O2的底物，它完全逆转了果糖对酒精代谢的抑制作用，表明果糖不是直接抑制过氧化氢酶。正如预期的那样，果糖使鹿鼠肝脏中的ATP/ADP比值从4.2±0.4显著降至2.4±0.4。这些数据与果糖通过抑制肝脏H2O2生成而降低体内过氧化氢酶依赖性乙醇代谢的假说一致。
