Formation of phenol and thiocatechol metabolites from bromobenzene premercapturic acids through pyridoxal phosphate-dependent C-S lyase activity.

K Lertratanangkoon, D Denney

Index: Biochem. Pharmacol. 45(12) , 2513-25, (1993)

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Abstract

When N-acetyl-S-(2-hydroxy-4-bromocyclohexa-3,5-dienyl)-L-cystein e (4-S-premercapturic acid) and N-acetyl-S-(2-hydroxy-5-bromocyclohexa-3,5-dienyl)-L-cystein e (3-S-premercapturic acid) were used as substrates in incubations with Hartley guinea pig kidney 9000 g supernatant preparations, the major products were the corresponding S-(2-hydroxy-4-bromocyclohexa-3,5-dienyl)-L-cysteine and S-(2-hydroxy-5-bromocyclohexa-3,5-dienyl)-L-cysteine. At the end of the incubation period, the percentage recovery of these N-deacetylate cysteine conjugates accounted for 77 +/- 2% of the substrates, 3-S- and 4-S-premercapturic acids. Removal of the N-acetyl group from premercapturic acids to form the corresponding cysteine conjugates by kidney N-deacetylase(s) showed no preference with respect to the 3-S- and 4-S-positional isomeric conjugates. Other metabolites which included the known sulfur-containing acids, mercaptolactate and mercaptoacetate, were also detected. 3- and 4-Bromophenol and 3- and 4-bromothioanisole were also formed. The addition of pyridoxal-5'-phosphate to the kidney incubation mixture resulted in a 5-fold increase in the formation of phenols and thioanisoles, along with four different isomeric O- and S-methylated 3-S-and 4-S-bromothiocatechols and two S-methylated 3-S- and 4-S-bromodihydrobenzene thiolols. This result indicated that a pyridoxal phosphate-dependent C-S lyase(s) is involved in the formation of both phenol and thiophenolic metabolites from S-(2-hydroxy-4-bromocyclohexa-3,5-dienyl)-L-cysteine and S-(2-hydroxy-5-bromocyclohexa-3,5-dienyl)-L-cysteine. Guinea pig liver 9000 g supernatant preparations did not N-deacetylate the 3-S- and 4-S-premercapturic acids to the same extent as kidney preparations, and this may account for decreased conversion of 3-S- and 4-S-premercapturic acids to 3- and 4-bromophenol and to thiophenolic products by liver preparations.