醛氧化酶在乙醇诱导的大鼠肝脏脂质过氧化中的作用。
The role of aldehyde oxidase in ethanol-induced hepatic lipid peroxidation in the rat.
作者信息
Shaw S, Jayatilleke E
机构信息
Department of Medicine, V.A. Medical Center, Bronx, NY 10468.
出版信息
Biochem J. 1990 Jun 15;268(3):579-83. doi: 10.1042/bj2680579.
Hepatic lipid peroxidation has been implicated in the pathogenesis of alcohol-induced liver injury, but the mechanism(s) by which ethanol metabolism or resultant free radicals initiate lipid peroxidation is not fully defined. The role of the molybdenum-containing enzymes aldehyde oxidase and xanthine oxidase in the generation of such free radicals was investigated by measuring alkane production (lipoperoxidation products) in isolated rat hepatocytes during ethanol metabolism. Inhibition of aldehyde oxidase and xanthine oxidase (by feeding tungstate at 100 mg/day per kg) decreased alkane production (80-95%), whereas allopurinol (20 mg/kg by mouth), a marked inhibitor of xanthine oxidase, inhibited alkane production by only 35-50%. Addition of acetaldehyde (0-100 microM) (in the presence of 50 microM-4-methylpyrazole) increased alkane production in a dose-dependent manner (Km of aldehyde oxidase for acetaldehyde 1 mM); menadione, an inhibitor of aldehyde oxidase, virtually inhibited alkane production. Desferrioxamine (5-10 microM) completely abolished alkane production induced by both ethanol and acetaldehyde, indicating the importance of catalytic iron. Thus free radicals generated during the metabolism of acetaldehyde by aldehyde oxidase may be a fundamental mechanism in the initiation of alcohol-induced liver injury.
肝脂质过氧化作用与酒精性肝损伤的发病机制有关，但乙醇代谢或由此产生的自由基引发脂质过氧化的机制尚未完全明确。通过测量乙醇代谢过程中分离的大鼠肝细胞中的烷烃生成量（脂质过氧化产物），研究了含钼酶醛氧化酶和黄嘌呤氧化酶在这类自由基生成中的作用。抑制醛氧化酶和黄嘌呤氧化酶（通过按每千克每天100毫克喂食钨酸盐）可使烷烃生成量减少（80 - 95%），而黄嘌呤氧化酶的显著抑制剂别嘌呤醇（口服20毫克/千克）仅使烷烃生成量减少35 - 50%。添加乙醛（0 - 100微摩尔）（在存在50微摩尔4 - 甲基吡唑的情况下）以剂量依赖方式增加烷烃生成量（醛氧化酶对乙醛的米氏常数为1毫摩尔）；醛氧化酶抑制剂甲萘醌几乎完全抑制烷烃生成。去铁胺（5 - 10微摩尔）完全消除了乙醇和乙醛诱导的烷烃生成，表明催化铁的重要性。因此，醛氧化酶在乙醛代谢过程中产生的自由基可能是酒精性肝损伤起始的一个基本机制。
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