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Biotransformation of Xenobiotics in Living Systems—Metabolism of Drugs: Partnership of Liver and Gut Microflora
Published in Peter Grunwald, Pharmaceutical Biocatalysis, 2020
The primary site of alcohol metabolism is the liver. The main pathway of ethanol metabolism involves its conversion to acetaldehyde, an oxidative reaction that is catalyzed by enzymes known as alcohol dehydrogenases. In a second reaction mediated by aldehyde dehydrogenase, acetaldehyde is oxidized to acetate (Fig. 6.7). Other enzymes, such as cytochrome P450 (e.g., CYP2E1), metabolize a small fraction of the ingested ethanol (Edenberg, 2007). Some drugs may inhibit the activity of aldehyde dehydrogenase leading to the accumulation of acetaldehyde during ethanol ingestion, which is associated with flushing, nausea and vomiting, palpitations and dyspnea. The well-known interaction is between disulfiram and ethanol. Because of its ability to cause these extremely unpleasant symptoms, disulfiram may be used to effectively treat alcohol dependence (Kitson, 1977). Other drugs that can cause disulfiram-like effects when administered concurrently with ethanol include chloramphenicol, furazolidone (Karamanakos et al., 2007) and some of cephalosporin antibiotics (Ren et al., 2014).
Overview of biological mechanisms of human carcinogens
Published in Journal of Toxicology and Environmental Health, Part B, 2019
Nicholas Birkett, Mustafa Al-Zoughool, Michael Bird, Robert A. Baan, Jan Zielinski, Daniel Krewski
‘Although alcoholic beverages may contain several potentially carcinogenic compounds, this synthesis focuses on the role of ethanol and acetaldehyde in the carcinogenesis associated with alcoholic beverages … … . The role of ethanol metabolism in tumour initiation is implied by the associations observed between different forms of cancer and polymorphisms in genes involved in the oxidation of ethanol. Whether, or to what degree, these associations are explained by redox changes, formation of radicals, effects on intermediary metabolism and/or effects on other pro-carcinogens cannot be established from current findings … . Acetaldehyde is a cytotoxic, genotoxic, mutagenic and clastogenic compound. It is carcinogenic in experimental animals’ (IARC 2012e, 470-1).