Cysteine detoxication

Another type of detoxication involves the production of cysteine conjugates, which are readily excreted. (Again, organomercury compounds show their affinity for -SH groups). Methyl mercuric cysteine is an important biliary metabolite in the rat and is degraded within the gut (presumably by microorganisms) to release inorganic mercury (see IAEA Report 137, 1972). 

As in the case of propachlor mercapturic acid sulfoxide, the biological significance of xenobiotic mercapturic acids that contain oxidized sulfur is not known. Casida et al. (39) have reported that sulfoxidation of some thiocarbamate herbicides is a beneficial step in the detoxication process. However, cysteine conjugates can exhibit adverse biological activities. Smith (40) has reviewed work on the metabolism of the toxic principle in kale and has shown that C-S lyase action on S-methylcysteine sulfoxide produces the toxic principle. Virtanen ( ) has reviewed the processes in other plants that lead to the production of compounds with biological activity from -substituted cysteine sulfoxides. 

These subsequent metabolic transformations are known to be involved in the nephrotoxicity of a number of compounds such as S-(l,2-dichlorovinyl)-L cysteine and hexachlorobu-tadiene (see chap. 7). Thus, although the initial glutathione conjugation may be a detoxication step, the final product of this phase 3 reaction may prove to be toxic. 

Peptides and proteins could be efficient metal binding ligands, because they have the functional groups for metal binding in their amino acid residues, and they can be produced at low cost by recombinant technologies. While many peptides and proteins are known to work as metal transport proteins in biological systems, metallothioneins (cysteine rich proteins with molecular weight of ca. 7 kDa) have attracted researchers attention for decades because they bind heavy metals in vivo [2]. The metallothioneins are considered to be involved in detoxication and metabolism of heavy metals. 

Keywords Glutathione Redox Cysteine Drug detoxication Metabolism ... 

Polypeptides (i.e., glutathione) Enzymes SH moiety of cysteine SH and NH Moieties lowered —y reduced GSH levels detoxication enhanced toxicity enzyme — inhibition altered metabolism denaturation altered membrane structure... 

Figure 9.7 Schematic representation of herbicide detoxification in a plant cell. Both XH and XZ are herbicides entering the oxidation-glucose conjugation pathway and the glutathione-dependent pathway, respectively. XOH is the hydroxylated herbicide XOGlc, XGS and Xcys are the glucose, GSH and Cysteine conjugates respectively. [Reproduced with permission of the authors from K. Kreuz and E. Martinoia, Herbicide Metabolism in Plants Integrated Pathways of Detoxication, in G. T. Brooks and T. R. Roberts, Eds., Pesticide Chemistry and Bioscience, The Food-Environment Challenge, Serial Pub. No. 233, The Royal Society of Chemistry, Cambridge, 1999, pp. 277-287.]...

It will be convenient to consider first the detoxication of artificial hydrogenation systems containing cysteine, which was detoxicated (Maxted, 8, 12 Maxted and Marsden, 13) by inducing the change ... 

Fig. 2. Detoxication of cysteine by its conversion to a shielded derivative. The figure shows hydrogenation runs carried out (a) with the poison in its original form, (b) with the poison after detoxication, and (c) with a hydrogenation system containing no poison.

Fig. 3. Detoxication of cysteine by various metallic per acids. Relationship is shown between the amount of detoxicant added and the percentage suppression of the toxicity of the poison. The curve obtained with the reagent containing a perti-tanate is abnormal in form, and the subsequent fall in the activity of the platinum catalyst may be due to cloaking by an insoluble deposit.

The detoxication of cysteine with different metallic per acids is illustrated in Fig. 3 in which the hydrogenation rate observed after the... 

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