Metabolism of estradiol by true and pseudoperoxidases.
The activation of 14C-labeled estradiol by "true" and "pseudo" peroxidases to form conjugates and other products was compared in four model systems using H2O2, glutathione, Mn2+ or irradiated riboflavin. Albumin was used as acceptor except in the glutathione system. The binding of estradiol to glutathione in the presence of the true peroxidases, lacto- or uterine peroxidase (no H2O2 added), was also examined and the conditions shown to differ from those required with the pseudoperoxidases, microperoxidase or trypsin-digested cytochrome c. The conjugates were purified by chromatography after elution from Amberlite XAD-2 and the relative amounts of these products assessed by autoradiography. The ratio of steroid to glutathione in the main water-soluble metabolite formed with lactoperoxidase was found to be approx 1:1 in a double label experiment with [14C]estradiol and [3H]glutathione. It was also shown, using estradiol labeled with 3H in different positions of the steroid molecule, that lactoperoxidase acts non-specifically in catalyzing the formation of glutathionyl conjugates as indicated by the release of 3H2O. The possible role of peroxidase and glutathione in the metabolism of estrogens and in the formation of artifactual products is discussed.
Jellinck
P H
PH
Perry
M
M
Løvsted
J
J
Newcombe
A M
AM
D000818:Animals; D002733:Chlorophenols / Q000494:pharmacology; D003574:Cytochrome c Group / Q000378:metabolism; D004958:Estradiol / Q000378:metabolism*; D005260:Female; D005978:Glutathione / Q000378:metabolism / Q000494:pharmacology; D006861:Hydrogen Peroxide / Q000494:pharmacology; D007784:Lactoperoxidase / Q000378:metabolism; D008345:Manganese / Q000494:pharmacology; D010544:Peroxidases / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D012256:Riboflavin / Q000494:pharmacology; D014599:Uterus / Q000201:enzymology
D002733:Chlorophenols; D003574:Cytochrome c Group; D008345:Manganese; D004958:Estradiol; D006861:Hydrogen Peroxide; D007784:Lactoperoxidase; D010544:Peroxidases; C021799:microperoxidase; D005978:Glutathione; C004762:2,4-dichlorophenol; D012256:Riboflavin