J. Biol. Chem., Vol. 261, Issue 17, 7729-7732, Jun, 1986
Absence of reactive intermediates in the formation of catechol estrogens by rat liver microsomes
PH Jellinck, EF Hahn and J Fishman
Release of 3H2O from regiospecifically labeled estradiol was measured
during 2-hydroxylation of this estrogen by rat liver microsomes. The amount
of tritium remaining in the isolated catechol estrogen was also determined.
Virtually all the tritium was removed from C-2 during the reaction
confirming the absence of an NIH shift. About 20% of the tritium at C-1 was
also lost without any such change occurring at C-4 or C-6,7 of the steroid
molecule. These findings provide evidence for the formation of an arene
oxide or o-semiquinone intermediate during the conversion of estradiol to
2-hydroxyestradiol. No indication of adduct formation at either C-1 or C-4
during this biotransformation was obtained although the 2-hydroxylated
product was able to react with a nucleophile such as glutathione. The
different regiospecificity of tritium loss in the generation of catechol
estrogens and in their subsequent reaction leads to the important
conclusion that the reactive intermediates in the two processes must be
different. The possible role of catechol estrogens in neoplastic
transformation is discussed.
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