2-hydroxyethynyloestradiol as a substrate for catechol-O-methyltransferase--implications in the metabolism of ethynyloestradiol.
Highly purified pig catechol-O-methyltransferase catalyses the methylation of 2-hydroxyethynyloestradiol (KM - 11.0 microM, Vmax = 521.2 mU/mg protein, Vmax/KM = 47.4) more efficiently than that of 2-hydroxyoestradiol (KM = 68.5 microM, Vmax = 1056.2 mU/mg protein, Vmax/Km = 15.4), 2-hydroxyoestrone (KM = 38.0 microM, Vmax = 795.0 mU/mg protein, Vmax/KM = 20.9) or 4-hydroxyoestrone (KM = 12.8 microM, Vmax = 159.7, Vmax/KM = 12.5). This efficient methylation of the principal metabolite of ethynyloestradiol substantiates the implications of the studies of Bolt et al.[1] that O-methylation is a major route of ethynyloestradiol metabolism. Furthermore, this also implies that catechol-O-methyltransferase in involved in the protection, by S-adenoysylmethionine, against the impairment of bile secretion by ethynyloestradiol, observed in female rats [2].
D000818:Animals; D002394:Catechol O-Methyltransferase / Q000378:metabolism*; D004997:Ethinyl Estradiol / Q000031:analogs & derivatives* / Q000378:metabolism*; D006863:Hydrogen-Ion Concentration; D007700:Kinetics; D008274:Magnesium / Q000378:metabolism; D013053:Spectrophotometry; D013552:Swine
D004997:Ethinyl Estradiol; C005933:2-hydroxyethynylestradiol; D002394:Catechol O-Methyltransferase; D008274:Magnesium