Zima T
I. ústav lékarské chemie a biochemie, 1. lékarská fakulta Univerzity Karlovy, Praha.
Sb Lek. 1993;94(4):281-7.
Three metabolic pathways of ethanol in human body have been described thus far: 1) alcohol dehydrogenase (ADH), 2) microsomal oxidizing ethanol system (MEOS), 3), catalase. The main role in alcohol metabolism is being payed by cytosolic enzyme, alcohol dehydrogenase, which catalyses metabolism of ethanol to acetaldehyde. It occurs in many dimeric isoenzyme forms which are divided into three classes, according to substrate specifics and other chemical-physical properties. ADH is regulated by development and sex, its activity has been described in many tissues (liver, stomach, kidneys, ovaria, uterus, testes, retina, iris). In 1991 Yoshida found a new gene of alcohol dehydrogenase-ADH 6. 4-hydroxyalkenals, cytotoxic products of lipid peroxidation, are also substrates of ADH. Acetaldehyde is further metabolised by aldehyde dehydrogenase (AIDH) to acetate. AIDH occurs in the form of several isoenzymes in cytosole, mitochondria and microsomes of almost all tissues. Acetaldehyde thus binds to nucleic acids, phospholipids and especially to proteins, it may change their structure and function. In activates collagen synthesis and stimulates lipid peroxidation. Human body may be impaired by immune reaction caused by acetaldehyde binding proteins. Acetaldehyde has the function of a hapten. In 1968 Lieber and DeCarli described microsomal ethanol oxidizing system (MEOS). MEOS is one of cytochrome P450 isoenzymes, now called P450IIE1. Having a gene on chromosome 10, composed of 492 amino acids, this isoenzyme is present in cytoplasmatic reticulum. It is inducible and in case of chronic alcoholism, it accelerates elimination of ethanol from the human body. Inducted P450IIE1 is also present in Kupffer cells which participate in fibrogenesis of liver tissue and produce interleukin 1.(ABSTRACT TRUNCATED AT 250 WORDS)
到目前为止,人体内乙醇的三种代谢途径已被描述:1)乙醇脱氢酶(ADH),2)微粒体乙醇氧化系统(MEOS),3)过氧化氢酶。乙醇代谢的主要作用由胞质酶乙醇脱氢酶发挥,它催化乙醇代谢为乙醛。它以多种二聚体同工酶形式存在,根据底物特异性和其他化学物理性质分为三类。ADH受发育和性别的调节,其活性在许多组织(肝脏、胃、肾脏、卵巢、子宫、睾丸、视网膜、虹膜)中都有描述。1991年,吉田发现了一种新的乙醇脱氢酶基因——ADH 6。4-羟基烯醛是脂质过氧化的细胞毒性产物,也是ADH的底物。乙醛进一步被乙醛脱氢酶(AIDH)代谢为乙酸。AIDH以几种同工酶的形式存在于几乎所有组织的胞质溶胶、线粒体和微粒体中。乙醛因此与核酸、磷脂尤其是蛋白质结合,可能改变它们的结构和功能。它会抑制胶原蛋白合成并刺激脂质过氧化。人体可能会因乙醛结合蛋白引起的免疫反应而受损。乙醛具有半抗原的功能。1968年,利伯和德卡利描述了微粒体乙醇氧化系统(MEOS)。MEOS是细胞色素P450同工酶之一,现在称为P450IIE1。该同工酶在10号染色体上有一个基因,由492个氨基酸组成,存在于内质网中。它是可诱导的,在慢性酒精中毒的情况下,它会加速人体对乙醇的清除。诱导的P450IIE1也存在于库普弗细胞中,这些细胞参与肝组织的纤维化形成并产生白细胞介素1。(摘要截取自250字)