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Basic Chemical Hazards to Human Health and Safety — I
Published in Jack Daugherty, Assessment of Chemical Exposures, 2020
Epoxides are extremely nucleophilic and chemical reactive. Many are carcinogens. Epoxide hydrolases detoxify epoxides. Amines, R–NH2, are oxidized to aldehydes and acids and conjugated to hydrophilic derivatives. Industrial nitro-derivatives, R-NO2, are reduced by hydroxylation. Aromatic hydrocarbons, halogenated aromatic hydrocarbons, and polycyclic hydrocarbons are detoxified by reaction with acetyl mercapturic acid, –SCH2CHCOOH. Inorganic and organic cyanides are neutralized by producing thiocyanate, RCNS. Glycine, –NHCH2COOH, metabolizes aromatic acids, aromatic-aliphatic acids, furane carboxylic acids, thiophene carboxylic acids, and polycyclic carboxylic acids (the Bile acids). Primary, secondary, and tertiary aliphatic and aromatic hydroxyl compounds are metabolized by glucuronate. Hydrazine derivatives are neutralized by glucose hydrazone.
Biomarkers in Occupational Neurotoxicology
Published in Lucio G. Costa, Luigi Manzo, Occupatinal Neurotoxicology, 2020
A number of enzymes involved in xenobiotic metabolism, for example, several members of the cytochrome P450 (CYP), glutathione transferase (GST) and N-acetyltransferase (NAT) families, display genetic polymorphisms.35,36 Many studies have revealed associations between a certain genotype and increased risk for smoking- or other xenobiotic-related cancers. For example, mutants of CYP1A1 and GSTM1 have been associated with an increased incidence of lung cancer, while slow acetylators (NAT2 mutants) have an increased risk for bladder cancer. Presumably, these individuals have an altered ability to metabolize polycyclic aromatic hydrocarbons and arylamines, respectively. Genetic polymorphisms have also been identified for other enzymes involved in xenobiotic metabolism, such as epoxide hydrolase, alcohol and aldehyde dehydrogenases, various esterases, and methyltrans-ferases.35,36
Hydrolytic Enzymes for the Synthesis of Pharmaceuticals
Published in Peter Grunwald, Pharmaceutical Biocatalysis, 2019
Sergio González-Granda, Vicente Gotor-Fernández
Microbial epoxide hydrolases (EHs) catalyse the addition of one molecule of water to epoxides, allowing their hydrolysis for the formation of the corresponding vicinal diols (Widersen et al., 2010; Bala and Chimni, 2010). The EH from Candida viswanathii has been reported to be an effective enzyme for the non-selective hydrolysis of 2-(phenoxymethyl)oxirane to form the racemic 3-phenoxy-1,2-propanediol, which is a useful precursor of β-adrenoblockers, cardiovascular drugs and anti-bacterial agents, among others (Meena and Banerjee, 2010). Whole cell form of the microorganism provided over 90% conversion after 15 h at 30°C using a mixture of a buffer pH 7 and ethanol (Scheme 9.16). Hydrolysis of 2-(phenoxymethyl)oxirane with a whole cell EH from Candida viswanathii
Xenobiotic metabolism and transport in Caenorhabditis elegans
Published in Journal of Toxicology and Environmental Health, Part B, 2021
Jessica H. Hartman, Samuel J. Widmayer, Christina M. Bergemann, Dillon E. King, Katherine S. Morton, Riccardo F. Romersi, Laura E. Jameson, Maxwell C. K. Leung, Erik C. Andersen, Stefan Taubert, Joel N. Meyer
Hydrolysis reactions use water to break a chemical bond. Enzymes that perform hydrolysis reactions are referred to as hydrolases. Xenobiotic-metabolizing hydrolases include esterases, amidases, and epoxide hydrolases. Of those, only epoxide hydrolases were studied in detail in C. elegans. Although humans express four epoxide hydrolase isoforms including both membrane-bound (microsomal) and soluble (cytosolic) forms, C. elegans possesses only two isoforms, ceeh-1 and ceeh-2 (Harris et al. 2008). These are most orthologous with the EH3 and EH4 human isoforms, which are the most recently discovered and least well characterized among human isoforms but are postulated to predominantly metabolize lipids. The C. elegans enzymes were confirmed to exhibit endobiotic and xenobiotic metabolizing activities, with ceeh-1 displaying higher activity toward substrates compared to ceeh-2 (Harris et al. 2008). Further studies are needed to establish the substrate specificity of both isoforms, particularly for xenobiotic substrates.