The major acidic metabolites of phenylalanine appearing in the urine of preweanling rats, after injection of uniformly labeled 14C-l-phenylalanine, were characterized by paper chromatography, by gas chromatography with trapping, and by mass spectrometer analysis of the metabolites separated by the gas chromatography. Very small amounts of phenyllactic acid and various phenolic acids were found. The major metabolites were hippuric acid and phenaceturic acid. Phenylalanine loading by injection of 340 mg/kg increased the metabolite excretion but did not alter the pattern. Pretreatment with pCP (60 mg/kg) did not alter the pattern of metabolites found, and only slightly altered their quantitative excretion. Similar results were found upon chronic pretreatment with a combination of pCP (60 mg/kg) and phenylalanine (340 mg/kg). On the other hand, when preweanling rats were pretreated with pCP and then given a larger dose of phenylalanine (4 g/kg), the classical unconjugated acidic products of phenylalanine appeared in the urine, the three major ones being phenyllactic acid, phenylpyruvic acid, and phenylacetic acid. The only metabolite of p-chlorophenylalanine found was p-chlorophenaceturic acid. These data indicate that the permanent neurologic damage incurred by the preweanling rat treated with pCP-plus-phenylalanine during the 21-day postnatal period is not associated with the accumulation of classical aromatic acidic metabolites.
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