Microsomal oxidations oxidative dehalogenation

The metabolism of 1,2,3-trichloropropane (11.27), an industrial solvent that undergoes biotransformation via dechlorination at C(l) and C(2) [60], is a clearer case of oxidative dehalogenation. Following incubation with human or rat liver microsomes, the compound was converted to 1,3-dichloroacetone (11.29), which could a priori be produced by oxidative dehalogenation (i. e., via 11.28) or by hydrolytic dehalogenation. In this study, evidence was found... 

Microsomal oxidations may be subdivided into aromatic hydroxylation aliphatic hydroxylation alicyclic hydroxylation heterocyclic hydroxylation N-, S-, and O-dealkylation N-oxidation N-hydroxylation S-oxidation desulfuration deamination and dehalogenation. 

Non-microsomal oxidations may be subdivided into amine oxidation, alcohol and aldehyde oxidation, dehalogenation, purine oxidation, and aromatization. 

Metabolism of the c/s and trans isomers of chlordane by humans and laboratory animals appears to be qualitatively similar (Kutz et al. 1976, 1979), although monkeys may be less efficient than rats (Khasawinah 1989), and rats may metabolize frans-nonachlor more efficiently than humans do (Tashiro and Matsumura 1978). Metabolism appears to be largely oxidative, involving hepatic microsomal cytochrome P-450 (Kawano et al. 1989). Epoxide hydrolase is probably the predominant enzyme involved in further degradation of oxychlordane, but the process appears to be slow in animals and humans. In addition, reductive dehalogenation, probably resulting in the formation of reactive free radical intermediates, may be important in the toxicity of chlordane (Brimfield and Street 1981 Kawano et al. 1989). 

Non-cytochrome P450 enzymes may also be involved in oxidative reactions. One such enzyme is alcohol dehydrogenase, whose substrates include vitamin A, ethanol, and ethylene glycol. Aldehyde dehydrogenase is another enzyme. Most reduction reactions also involve microsomal enzymes, with the exception of ketone reduction. Nitro compounds are reduced to amines, and volatile anesthetics undergo dehalogenation by microsomal enzymes. Hydrolysis reactions are involved in the metabolism of compoimds with amide bonds or ester linkages, as in the conversion of aspirin to salicylate (Brown, 2001). 

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