An in vivo function of glucagon-lnduced phenylalanine: Pyruvate transaminase in p-chlorophenylalanine-treated rats

The effect of glucagon-induced phenylalanine:pyruvate transaminase on the urinary excretion of the unconjugated metabolites of phenylalanine transamination was studied in rats. Chronic injection of glucagon induced an 18-fold increase in hepatic phenylalanine:pyruvate transaminase activity. Treatment with p-chlorophenylalanine (PCPA) blocked phenylalanine hydroxylase and caused an elevation of plasma phenylalanine following administration of an intraperitoneal loading dose of this amino acid. Gasliquid Chromatographic analysis demonstrated the presence of phenylpyruvate, phenyllactate, and O-hydroxyphenylacetate in the urine of PCPA- and PCPA-glucagontreated rats, but not control or glucagon-treated animals. Combined PCPA-glucagon treatment caused twofold increase in phenylpyruvate and phenyllactate concentrations and a fivefold increase in O-hydroxyphenylacetate concentration, when compared to urinary metabolite levels from rats receiving only PCPA treatment. A decrease in plasma phenylalanine was found together with the elevated urinary levels of the phenylalanine transamination metabolites. The results provide the first evidence that the unconjugated transamination metabolite concentrations increase when concurrent treatment with glucagon causes high-level induction of hepatic phenylalanine:pyruvate transaminase.