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 ( k M = 11.0 μM, V max = 521.2 mU/mg protein, V max k M = 47.4) more efficiently than that of 2-hydroxyoestradiol ( k M = 68.5 μM, V max = 1056.2 mU/mg protein, V max K m = 15.4) , 2-hydroxyoestrone ( k M = 38.0 μM, V max = 795.0 mU/mg protein, V max K M = 20.9) or 4-hydroxyoestrone ( K M = 12.8 μM), V max = 159.7, V max K M = 12.5 ). This efficient methylation of the principal metabolite of ethynyloestradiol substantiates the implications of the studies of Bolt et al.[l] that O-methylation is a major route of ethynyloestradiol metabolism. Furthermore, this also implies that catechol- O-methyltransferase is involved in the protection, by S-adenosylmethionine. against the impairment of bile secretion by ethynyloestradiol, observed in female rats [2].