Quinol-based metabolic cycle for estrogens in rat liver microsomes

Laszlo Prokai, Katalin Prokai-Tatrai, Pal Perjesi, Alevtina D. Zharikova, James W. Simpkins

Research output: Contribution to journalArticlepeer-review

24 Scopus citations

Abstract

According to a recently reported metabolic pathway, phenolic A-ring estrogens are metabolized in rat liver microsomes partially to the corresponding quinols by cytochrome P450 isoenzymes. We found that these quinols could, in turn, undergo reduction to regenerate the parent estrogens consumed during the metabolic process. Among the tested endogenous reducing agents, NADH and especially NADPH produced a significant extent of reductive conversion. Enzymes available in rat liver microsomes further catalyzed this reaction with 6.5 ± 1.5 nmol · min-1 · (mg of protein)-1 measured as the initial rate of estrone formation at 37°C, whereas the initial rate of second-order reaction for the reduction of E1-quinol by a 10-fold excess of NADPH in a microsome-free buffer solution and under identical incubation conditions was 0.62 ± 0.03 nmol · min-1. The quinol route is, therefore, unique among estrogen-metabolizing pathways for its bioreversibility due to the facile regeneration of the phenolic A-ring estrogens consumed in the preceding oxidative process.

Original languageEnglish
Pages (from-to)701-704
Number of pages4
JournalDrug Metabolism and Disposition
Volume31
Issue number6
DOIs
StatePublished - 1 Jun 2003

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