Mercapturic acids, biosynthesis

Conjugation UDP-glucuronosyltransferase Sulfotransferase Glutathione S-transferase Mercapturic acid biosynthesis Cysteine conjugate /i-lyase/thiomethylase W-Acetyltransferase W-Methyltransferase O-Methyltransferase... 

Although mercapturic acids are normally the major thioether products of lipophilic xenobiotics found in urine of mammals, small amounts of the corresponding S-cysteine conjugates are also frequently excreted. All four thioether products formed during mercapturic acid biosynthesis are routinely excreted in bile. 

Figure 12 Mercapturic acid biosynthesis from a naphthaiene 1,2-oxide. Oniy one of fhe isomers resuifing from reacfion of GSH wifh fhe arene oxide is shown. (1) giufafhione S-transferase, (2) y-giufamyifranspepfidase, (3) cysfeinyigiycinase acfivify (dipepfidases), and (4) A/-acefyifransferase.

Whereas the GST were studied originally because of their involvement in mercapturic acid biosynthesis, these enzymes are also currently of interest to researchers working in fields other than toxicology. Some of the research areas in which GST are of importance include tumor markers, inherited cancer susceptibility, drug resistance, biotechnology, and clinical biochemistry. 

B40. Boyland, E., and Chasseaud, L. F., The role of glutathione and glutathione S-transferases in mercapturic acid biosynthesis. Adv. Enzymol 32, 173-219 (1969). 

Fig. 3. GSH conjugation with the electrophilic compound RX, followed by mercapturic acid biosynthesis to yield the NAcCys conjugate as the final product.

D. Glutathione conjugation and mercapturic acid biosynthesis Glutathione-S-transferases Epoxides, haloalkanes, nitroalkanes, alkenes and aromatic halo-and nitro-compounds R-X + GSH R-SG + X where RX is a xenobiotic with an electrophilic centre and GSH in glutathione. Conjugates can be further metabolized to mercapturic acids... 

Kaye CM. 1973. Biosynthesis of mercapturic acids from allyl alcohol, allyl esters, and acrolein. Biochem J 134 1093-1101. 

The more complex sulphur requirements of the marine animals are met largely by cysteine, cystine, methionine, biotin, and thiamine (Young and Maw, 1958) (Fig. 4). Cysteine is a component of the tripeptide glutathione and a precursor of taurine. Methionine is as an essential amino acid involved in biosynthesis of proteins, creatine and adrenaline. Adenosylmethionine is considered to be the active part in transmethylation, e.g. of choline. Methionine is part of the pathways to homocysteine, cystathionine and methylthioadenosine (Young and Maw, 1958). Various organisms convert cysteine and/or cystine into mercapturic acids, cysteine sulphinic acid, and thiazolidine derivatives (Zobell, 1963). 

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