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
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.