Mercapturic acid, conjugation derivatives

Atrazine, used as a selective pre- and post-emergence herbicide to control annual weeds in several crops, is the most representative compound of this group. It is also used as a non-selective herbicide in non-crop areas. After absorption, the compound is metabolized to dealkylated and deisopropy-lated derivatives. The unchanged compound and its metabolites are excreted in urine, where they can be detected by chromatography or enzyme-linked immunosorbent assay (Lucas et al., 1993). A mercapturic acid conjugate of atrazine has also been found in urine samples of workers spraying this herbicide (Lucas et al., 1993) (Table 6). 

The principal mercapturic acid derivative, N-acetyl-S-(2-hydroxyethyl-)L-cysteine, and other related metabolites are derived from the conjugation reaction of 1,2-dibromoethane with glutathione, a molecule present in mammalian cells. This suggests that the primary pathway of... 

Male Wistar rats given single oral doses of 10, 50, or 250 mg/kg of1,4-dichlorobenzene (vehicle not given) excreted the majority of derived from 1,4-dichlorobenzene in the urine as either the sulfate conjugate (60%) or the glucuronide (30%). Bile contained 5 and 30% of the total radioactivity after the low and high doses, respectively. Only minor amounts of mercapturic acid were found (Hissink et al. 1997). 

Burka et al. (1994) examined the effect of treatment of rats with phenobarbital and SKF-525A on the urinary metabolite profile of [2- - C]aciy lonitnle. Phenobarbital treatment increased the excretion of products attributed to the oxidation of acrylonitrile to CEO, while SKF-525A treatment enhanced the excretion of the mercapturic acid derived from the glutathione conjugation of acrylonitrile itself. 

Mercapturic acid derivatives have been isolated following the administration of hydrocarbons, monohalogenated benzenes,1 and cyanoben-zene124 and one may be produced from nitrobenzene.123 A relationship to perhydroxylation was anticipated in 1932 by Rhode,127 who suggested that bromobenzene is oxidized to p-bromophenol, which undergoes ring reduction and conjugation to form the intermediate XVI. 

GSH conjugation reaction. The GSH conjugate products, however, arc not metabolized to mercapturic acids but instead are converted enzymatically to the corresponding alcohol derivatives and glutathione disulFidc (GSSG). "... 

In mammals, GSH S-conjugates, the metabolites of GSH S-transferase catalyzed reactions, are subject to further metabolism by a series of three enzyme-catalyzed reactions to form the corresponding N-acetylcysteine derivative or mercapturic acid, which is excreted in urine (3). The same group of three enzymes are also involved in recycling of GSH and in amino acid transport. The first step is catalyzed by y-glutamyltransferase (EC 2.3.2.2), an enzyme localized on the outer surface of most cells. This enzyme has been detected in A. suum (57), S. mansoni (58) and T. cruzi epimastigotes (59). However, there is no evidence that parasites metabolize GSH... 

Traditionally, the hydroxylation of aromatic compounds by CYP450 has been considered to be mediated by an arene oxide (epoxide) intermediate followed by the NIH shift," as discussed previously (29,30,31) (Fig. 10.6). The formation of phenols and fhe isolation of urinary dihydrodiols, catechols, and glutathione conjugates (mercapturic acid derivatives) implicates arene oxides as intermediates in the metabolism of benzene and substituted benzenes in mammalian systems. The arene oxides... 

Acetaminophen administered to animals is excreted mainly as its glucuronide and its sulfate conjugate ( ), but a small amount of the drug is excreted as its mercapturic acid and cysteine derivatives in all animals studied including man (16) (Fig.2). 

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