Gemma Simonetta, Vichi Susanna, Testai Emanuela
Dipartimento di Ambiente e Connessa Prevenzione Primaria, Istituto Superiore di Sanità, Rome, Italy.
Ann Ist Super Sanita. 2006;42(1):8-16.
The large interethnic and interindividual variability in alcohol-induced toxic effects comes from a combination of genetic and environmental factors, influencing ethanol toxicokinetics. The hepatic enzymatic systems involved in ethanol metabolism are alcohol dehydrogenase (ADH), aldehyde dehydrogenase (ALDH) and microsomal P4502E1 (CYP2E1). ADH oxidizes ethanol to acetaldehyde, which is very efficiently oxidized to acetate by ALDH. About 10% of moderate quantities of ethanol is metabolised by CYP2E1; the percentage increases when ADH is saturated. During ethanol metabolism reactive oxygen species and hydroxyethyl radicals are generated, causing oxidative stress, responsible for most ethanol-induced liver damage. For their critical role in detoxifying radicals, glutathione S-transferase are gaining attention in the etiology of alcoholism. All these enzymes have been shown to be polymorphic, giving rise to altered phenotypes. For this reason recent studies have looked for a correlation between metabolic variability and differences in alcohol abuse-related effects.
酒精诱导的毒性效应在不同种族和个体之间存在很大差异，这是由遗传和环境因素共同作用导致的，这些因素会影响乙醇的毒代动力学。参与乙醇代谢的肝脏酶系统包括乙醇脱氢酶（ADH）、乙醛脱氢酶（ALDH）和微粒体P4502E1（CYP2E1）。ADH将乙醇氧化为乙醛，乙醛再被ALDH非常有效地氧化为乙酸。约10%的适量乙醇由CYP2E1代谢；当ADH饱和时，这一比例会增加。在乙醇代谢过程中会产生活性氧和羟乙基自由基，从而导致氧化应激，这是大多数乙醇诱导的肝损伤的原因。由于谷胱甘肽S-转移酶在清除自由基方面的关键作用，它们在酒精中毒的病因学中受到了关注。所有这些酶都已被证明具有多态性，从而导致表型改变。因此，最近的研究一直在寻找代谢变异性与酒精滥用相关效应差异之间的相关性。
