Mercapturic acid precursors.

Although we have demonstrated previously that tissue slices are capable of carrying out a complete synthesis of p-iodophenylmercapturic acid (l), the intermediate compounds and the mechanisms involved in forming the link between the aromatic ring and cysteine sulfur have remained obscure. Various workers have suggested that a primary step is an attachment of the hydrocarbon to the sulfur of a protein. Stekol (2), after studying the effect of dietary cystine and methionine on the yield of mercapturic acids, concluded that halogen-substituted hydrocarbons react initially with tissue sulfur. From their studies with 8Wlabeled amino acids, Gutmann and Wood (3) also arrived at the conclusion that tissue-bound rather than free amino acid sulfur is the primary source for mercapturic acids. The final step in mercapturic acid synthesis generally has been assumed to be acetylation of the amino group of an arylcysteine. Thus, in every case, the administration of an arylor alkylarylcysteine to intact animals has been followed by excretion of the corresponding mercapturic acid (4, 5). Also, tissue slices converted benzylhomocysteine and p-bromophenylcysteine to mercapturic acids (6). The present report describes the isolation of radioactive p-iodophenylcysteine as well as p-iodophenylmercapturic acid following incubation of iodobenzene-1131 with rat liver slices. After oral administration of iodobenzene-P31 to the rat, p-iodophenylcysteine was found in the liver, intestine, and kidney, but none was present in the urine. These observations establish the role of p-iodophenylcysteine as a direct precursor of p-iodophenylmercapturic acid in the metabolic detoxication of iodobenzene. Evidence has been obtained also for the presence in liver and intestine of other precursors of p-iodophenylmercapturic acid. Following oral administration of iodobenzene-1131, tissue proteins labeled with radioactivity have been isolated. Presumably the proteins contained p-iodophenyl groups attached to cysteine residues. The interpretation of these results may be considered to be equivocal because it depends upon the complete removal of absorbed radioactive molecules by standard washing procedures (7).