FORMATION OF PHENOL AND THIOCATECHOL METABOLITES FROM BROMOBENZENE PREMERCAPTURIC ACIDS THROUGH PYRIDOXAL PHOSPHATE-DEPENDENT C-S LYASE ACTIVITY

Citation
K. Lertratanangkoon et D. Denney, FORMATION OF PHENOL AND THIOCATECHOL METABOLITES FROM BROMOBENZENE PREMERCAPTURIC ACIDS THROUGH PYRIDOXAL PHOSPHATE-DEPENDENT C-S LYASE ACTIVITY, Biochemical pharmacology, 45(12), 1993, pp. 2513-2525
Citations number
22
Categorie Soggetti
Pharmacology & Pharmacy",Biology
Journal title
ISSN journal
00062952
Volume
45
Issue
12
Year of publication
1993
Pages
2513 - 2525
Database
ISI
SICI code
0006-2952(1993)45:12<2513:FOPATM>2.0.ZU;2-M
Abstract
When (2-hydroxy-4-bromocyclohexa-3,5-dienyl)-L-cysteine (4-S-premercap turic acid) and (2-hydroxy-5-bromocyclohexa-3,5-dienyl)-L-cysteine (3- S-premercapturic acid) were used as substrates in incubations with Har tley guinea pig kidney 9000 g supernatant preparations, the major prod ucts were the corresponding (2-hydroxy-4-bromocyclohexa-3,5-dienyl)-L- cysteine and 2-hydroxy-5-bromocyclohexa-3,5-dienyl)-L-cysteine. At the end of the incubation period, the percentage recovery of these N-deac etylate 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 nopreference with respect to the 3-S- and 4-S-positional isomeric conjugates. Other metabolites which includ ed the known sulfur-containing acids, mercaptolactate and mercaptoacet ate, were also detected. 3- and 4-Bromophenol and 3- and 4-bromothioan isole were also formed. The addition of pyridoxal-5'-phosphate to the kidney incubation mixture resulted in a 5-fold increase in the formati on 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 format ion of both phenol and thiophenolic metabolites from S-(2-hydroxy-4-br omocyclohexa-3,5)-L-cysteine and 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 exten t as kidney preparations, and this may account for decreased conversio n of 3-S- and 4-S-premercapturic acids to 3- and 4-bromophenol and to thiophenolic products by liver preparations.