American Journal of Clinical Nutrition, Vol 24, 699-703, Copyright © 1971 by The American Society for Clinical Nutrition, Inc.

Abnormal tryptophan metabolism in pregnancy and with the oral contraceptive pill. I. Specific effects of an oral estrogenic contraceptive steroid on the tryptophan oxygenase and two aminotransferase activities in livers of ovariectomized-adrenalectomized rats

¹ From the Department of Biochemical Nutrition, Hoffmann-La Roche Inc., Nutley, New Jersey. This work was done partially in the Departments of Biochemistry and Medicine at the Upstate Medical Center, State University of New York, Syracuse, N.Y.

Both tryptophan oxygenase and pyruvic aminotransferase activities are reduced in rat liver by ovariectomy, and restored by feeding an estrogenic contraceptive steroid (ethinylestradiol). In the ovariectomized-adrenalectomized rat, however, the estrogenic steroid restored tryptophan oxygenase activity to normal and had no effect on the aminotransferase enzyme.

The findings explain two additional aspects of increased vitamin B₆ needs in pregnancy and in women on oral contraceptive steroids as demonstrated by abnormal tryptophan load tests. a) The direct effect of estrogenic steroids in increasing tryptophan oxygenase activity results in increased tryptophan metabolites, thereby stressing the capacity of the vitamin B₆-related enzymes to convert these substrates toward niacin. b) Induced synthesis of aminotransferase enzymes subsequent to elevated plasma glucocorticoid levels under these conditions results in increased availability of pyridoxal phosphate binding sites. At marginal pyridoxine intake this may result in partial removal of coenzyme from the vitamin B₆-requiring enzymes in the tryptophan-niacin pathway.

These findings, when coupled to c) observations of others who demonstrated a desaturation of kynurenine aminotransferase for pyridoxal phosphate following estrogen administration, and d) the compartmentalization of vitamin B₆ in the fetus, serve to provide a biochemical basis for increased pyridoxine needs in pregnancy and in women on the pill.