Glutathione conjugation intermediate xenobiotic

A biological difference that could increase susceptibility of fetuses and premature or perinatal infants to 1,2-dibromoethane toxicity is developmental immaturity of the P-450 (microsomal enzyme) system. Biotransformation of xenobiotics occurs predominantly by glutathione conjugation (Benet and Sheiner 1985 Sipes and Gandolfi 1986). This pathway is known to generate a number of toxic intermediate metabolites of 1,2-dibromoethane. In addition, fetal mice have selective binding of... 

The oxidation of naphthalene was one of the earliest examples of an epoxide as an intermediate in aromatic hydroxylation. As shown in Figure 7.3, the epoxide can rearrange nonenzymatically to yield predominantly 1-naphthol, or interact with the enzyme epoxide hydrolase to yield the dihydrodiol, or interact with glutathione S-transferase to yield the glutathione conjugate, which is ultimately metabolized to a mercapturic acid. These reactions are also of importance in the metabolism of other xenobiotics that contain an aromatic nucleus, such as the insecticide carbaryl and the carcinogen benzo(a)pyrene. 

Figure 7.10 Glutathione conjugate of a xenobiotic species (HX-R), followed by formation of glutathione and cysteine conjugate intermediates (both of which may be excreted in bile) and acetylation to form readily excreted mercapturic acid conjugate.

Arylpropionic acid (2-APA) nonsteroidal anti-inflammatory drugs (NSAlDs) provide one of the most studied illustrated pharmaceutical examples of inversion by conjugation through a coenzyme A (CoA) thioester intermediate. It is also possible that bioinversion of xenobiotics proceed through other conjugation mechanisms such as glutathione [1 ]. 

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