Mercapturic acid, conjugation

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). 

FIGURE 7.18 Reaction scheme by which glutathione conjugates are converted to mercapturic acid conjugates. 

Apart from glucuronic acid and sulfate conjugation of hydroxycoumarins, other phase II pathways of coumarin metabolism have been identified. For example, ortho-coumaric acid may be conjugated with glycine (Lake, 1999), and a coumarin mercapturic acid conjugate has also been reported (Huwer et al., 1991). Coumarin may also be metabolized by the gastrointestinal microflora to 3,4-dihydrocoumarin and ort/io-hydroxyphenylpropionic acid under anaerobic conditions (Scheline, 1968). 

Mraz and Nohova (1992b) placed 10 volunteers (5 men, 5 women) in atmospheres of 10, 30 and 60 mg/m dimethylformamide for 8 h and measured the metabolites in urine collected for up to five days. In addition, two men and two women were exposed to 30 mg/m for 8 h per day on five consecutive days. The uptake from the respiratory tract was 90% and the various urinary metabolites examined accounted for 49% of the retained dose. The half-lives of excretion and the urinary recoveries of the metabolites were dimethylformamide, 2 h (0.3% of dose) y-hydroxymcthyl-V-mcthylformamide, 4 h (22%) jV-hydroxymethylfonnamide, 7 h (13%) and the mercapturic acid conjugate, A -acet l-.S -(V-mcthylcarbamoyl)cystcinc, 23 h (13%). 

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.

Acetylation reactions catalyzed by acetyltransferase enzymes involve the attachment of the acetyl moiety, shown as the final step in glutathione conjugation and the production of a mercapturic acid conjugate in Figure 7.10. The cofactor upon which the acetyltransferase enzyme acts in acetylation is acetyl coenzyme A ... 

L-Cysteine, N-acetyl-S-(3,4-dihydroxybutyl) mercapturic acid conjugate... 

How are mercapturic acid conjugates formed What special role do they play in biological monitoring What advantage do they afford in terms of measurement ... 

Glucuronide and sulphate conjugates, and the cysteine and mercapturic acid conjugates (formed from inactivation of NAPQI by glutathione), are excreted in the urine. 

Lamoureux and Davison (1975), investigating the metabolism of propachlor in rats, found that here too the mercapturic acid pathway plays an important role. Rats treated with -propachlor excerted 20% of the dose in the form of mercapturic acid conjugate 24 hours after treatment ... 

Structural Alerts The term refers to a metabolite that belongs to a chemical class with known toxicity, a metabolite that contains positive structural alerts for certain toxicity, or a GSH adduct/mercapturic acid conjugate indicative of a trapped reactive intermediate. 

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