The role of pteroylglutamic acid in tyrosine oxidation by rat liver tissue.

In so far as their function in nutrition is defined, the vitamins have been found to be essential components of several enzyme systems (1). In this connection there is evidence that the vitamin, pteroylglutamic acid (PGA), is necessary in an enzyme system concerned with oxidation of the amino acid tyrosine. Experiments have shown that livers from rats with a PGA deficiency produced by incorporating succinylsulfathiazole in the diet have a lowered capacity to oxidize tyrosine (2), and that tyrosine metabolites disappear from the urine of vitamin C-deficient guinea pigs when PGA is administered (3). More indirect is the evidence that untreated pernicious anemia patients, who presumably are deficient in PGA (4), cannot properly oxidize tyrosine (5). It is the purpose of this paper to present in detail our experiments on the oxidation of tyrosine by liver tissue from rats with a PGA deficiency induced by succinylsulfathiazole (2). It will be shown that the rate of tyrosine oxidation for these livers is lower than for normal liver and that the rate can be increased by the addition of PGA, but not by pteroylheptaglutamic acid, a naturally occurring conjugate of PGA, or by liver extract containing the antipernicious anemia (APA) principle. These results will be compared and contrasted with those obtained in a new series of experiments in which the PGA inhibitor 4-aminopteroylglutamic acid is employed to produce a PGA deficiency state.