The effect of pteroylglutamic acid and related compounds upon tyrosine metabolism in the scorbutic guinea pig.

The ingestion of large amounts of aromatic amino acids included in diets practically devoid of ascorbic acid results in the urinary excretion of several intermediary metabolites of these substances in both guinea pigs (1, 2) and premature infants (3). The abnormal constituents of the urine following tyrosine ingestion have been identified as p-hydroxyphenylpyruvic acid, p-hydroxyphenyllactic acid, and small amounts of tyrosine (1, 3). Homogentisic acid has also been recovered from guinea pig urine (1). The degree of hydroxyphenyluria observed seems to depend upon the duration of the scorbutigenic regime as well as the amount of tyrosine ingested (2). This apparent defect in tyrosine metabolism disappears following the administration of small amounts of Z-ascorbic acid (1, 2, 4). The failure of d-isoascorbic acid to produce the same effect, except in doses 20 times that of the naturally occurring isomer (l), suggests that the vitamin C activity of this compound is the essential property involved. This hypothesis is confirmed by the observation of transitory and minimal responses following the administration of several dicarboxylic acids of the Krebs cycle (5) and liver extract (4, 6) as well as the failure of the longer recognized components of the vitamin B complex to influence the metabolic aberration. The reports that pteroylglutamic acid (PGA) increased the oxidation of tyrosine by suspensions of liver from sulfonamide-treated rats (7) and that the high excretion of phenolic compounds by patients having pernicious anemia in relapse was reduced by liver therapy (8) suggested to us that PGA might have an effect upon the tyrosine metabolism of the scorbutic guinea pig. Results have been presented demonstrating that PGA abolishes the hydroxyphenyluria of tyrosine-fed guinea pigs on a scorbutigenie diet (9). This report provides additional details of the methods employed in these studies and presents further studies showing the pre-