RESEARCH FROM ANIMAL TESTING TO CLINICAL EXPERIENCE
Individual susceptibility and alcohol effects:biochemical and genetic aspects
Simonetta Gemma, Susanna Vichi and Emanuela Testai
Dipartimento di Ambiente e Connessa Prevenzione Primaria, Istituto Superiore di Sanità, Rome, Italy
Summary. 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.
Key words: ethanol, interindividual variability, polymorphism, alcohol dehydrogenase, aldehyde dehydrogenase, CYP2E1, glutathione S-transferase.
Source: ANN IST SUPER SANITÀ 2006, VOL. 42, NO. 1: 8-16