PHENYLALANINE METABOLISM AND FOLIC ACID ANTAGONISTS*

Abstract

Oral phenylalanine tolerance tests were performed on women before and after treatment with amethopterin for choriocarcinoma. The folic acid antagonist resulted in higher serum phenylalanine levels, slower rates of decay of serum phenylalanine, and smaller increments in serum tyrosine levels after oral administration of phenylalanine. These changes did not correlate with the therapeutic or toxic effects of the drug. Phenylpyruvic acid was not excreted in the urine when L-phenylalanine was fed. The changes in phenylalanine tolerance appeared within 12 hours of amethopterin administration, and lasted at least 2 weeks. Folic acid-deficient diets were fed to weanling rats for 7 weeks. Those which demonstrated gross folic acid deficiency and inanition had 36% lower values of cofactor for phenylalanine hydroxylase in their livers than had controls fed folic acid. The findings support a role for pteridine cofactors and their enzymatic activation in the conversion of phenylalanine to tyrosine in humans.