RT Journal Article
SR Electronic
T1 Enantioselective S-oxygenation of para-methoxyphenyl-1,3-dithiolane by various tissue preparations: effect of estradiol.
JF Molecular Pharmacology
JO Mol Pharmacol
FD American Society for Pharmacology and Experimental Therapeutics
SP 319
OP 327
VO 37
IS 2
A1 J R Cashman
A1 L D Olsen
A1 C E Lambert
A1 M J Presas
YR 1990
UL http://molpharm.aspetjournals.org/content/37/2/319.abstract
AB Liver, kidney, and lung microsomes prepared from nonpretreated female Sprague-Dawley rats catalyze the NADPH- and oxygen-dependent S-oxygenation of para-methoxyphenyl-1,3-dithiolane. Studies on the biochemical mechanism of dithiolane S-oxygenation in liver, kidney, and lung microsomes suggest that this reaction is catalyzed in a diastereoselective and enantioselective fashion by the flavin-containing monooxygenase and, to a lesser extent, the cytochromes P-450. This conclusion is based on results examining the effects of selective cytochrome P-450 inhibitors and positive effectors, microsome heat-inactivation treatment, and alternate substrates for the flavin-containing monooxygenase. Liver and kidney microsomes prepared from ovarectomized female rats tended to have decreased S-oxygenase activity, compared with nonpretreated female rats, whereas ovarectomized rats pretreated with estradiol had markedly lower S-oxygenase activity. In contrast, lung microsomal S-oxygenase activity, which is low in pulmonary microsomes from nonpretreated female rats, increases 2-4-fold after ovariectomization and estradiol pretreatment. In female Sprague-Dawley rats, estradiol pretreatment is mainly responsible for the large decrease (or increase) in S-oxygenase activity observed in the tissues examined, although it is unlikely that estradiol alone controls flavin-containing monooxygenase S-oxygenase activity.