Oxidation xenobiotic transformations

Phosphorothioates and phosphonothioates are of particular significance as insecticides. Schematically, it can be stated that these xenobiotics undergo activation by oxidative desulfuration, and detoxification by hydrolytic cleavage. Oxidative desulfuration transforms phosphorothioates and phosphonothioates to the corresponding oxon derivatives (see Chapt. 7 in [59]), which are highly toxic as potent inactivators of acetylcholinesterase [69]. This route of toxification can be competitive with and/or followed by cleavage reactions, which can be either hydrolytic or oxidative. 

Polymerization, or conjugation, is the process in which toxic organic molecules undergo microbially mediated transformation by oxidative coupling reactions. In this case, a contaminant or its intermediate product(s) combines with itself or other organic molecules (e.g., xenobiotic residues, naturally occurring compounds) to form larger molecular polymers that can be incorporated in subsurface humic substances. 

In mammalian liver microsomes, cytochrome P-450 is not specific and catalyzes a wide variety of oxidative transformations, such as (i) aliphatic C—H hydroxylation occurring at the most nucleophilic C—H bonds (tertiary > secondary > primary) (ii) aromatic hydroxylation at the most nucleophilic positions with a characteristic intramolecular migration and retention of substituents of the aromatic ring, called an NIH shift,74 which indicates the intermediate formation of arene oxides (iii) epoxidation of alkenes and (iv) dealkylation (O, N, S) or oxidation (N, S) of heteroatoms. In mammalian liver these processes are of considerable importance in the elimination of xenobiotics and the metabolism of drugs, and also in the transformation of innocuous molecules into toxic or carcinogenic substances.75 77... 

Biotransformation refers to changes in xenobiotic compounds as a result of enzyme action. Reactions not mediated by enzymes may also be important. As examples of nonenzymatic transformations, some xenobiotic compounds bond with endogenous biochemical species without an enzyme catalyst, undergo hydrolysis in body fluid media, or undergo oxidation-reduction processes. However, the metabolic phase I and phase II reactions of xenobiotics discussed here are enzymatic. 

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