title: Glucagon stimulation of phenylalanine metabolism. The effects of acute and chronic glucagon treatment.
abstract: The effects of acute and chronic glucagon treatment on phenylalanine metabolism in vivo in the rat have been investigated. A single, large dose of glucagon (2 mg/kg, i.p.) increased metabolism of a large load of phenylalanine (1.27 g/kg) via hydroxylation and transamination. The increased metabolism was associated with increased activities of hepatic phenylalanine:pyruvate aminotransferase, tyrosine aminotransferase and phenylalanine hydroxylase. In rats administered this amount of phenylalanine, the p-hydroxyphenylpyruvate dioxygenase reaction was apparently rate limiting, as indicated by increased urinary excretion of p-hydroxyphenylpyruvate and p-hydroxyphenyllactate, in addition to urinary excretion of phenylpyruvate and phenyllactate. Chronic glucagon treatment (1.25 mg/kg every 12 hr for 8 days) increased oxidation of the large phenylalanine load and urinary excretion of phenylpyruvate and phenyllactate but not p-hydroxyphenylpyruvate or p-hydroxyphenyllactate. The increased excretion of phenylpyruvate and phenyllactate was associated with an increase in hepatic phenylalanine: pyruvate aminotransferase activity. The absence of p-hydroxyphenylpyruvate in the urine and the increased oxidation of phenylalanine imply that, in rats administered glucagon chronically, flux of p-hydroxyphenylpyruvate through the p-hydroxyphenylpyruvate dioxygenase reaction was increased. A kinetic assay for phenylalanine hydroxylase based on measurement of oxygen consumption in described.
mesh_terms: D000596:Amino Acids / Q000378:metabolism; D000818:Animals; D005934:Glucagon / Q000008:administration & dosage / Q000494:pharmacology*; D007651:Keto Acids / Q000652:urine; D008099:Liver / Q000201:enzymology; D008297:Male; D008956:Models, Chemical; D010084:Oxidation-Reduction; D010649:Phenylalanine / Q000378:metabolism*; D010651:Phenylalanine Hydroxylase / Q000378:metabolism; D011773:Pyruvates / Q000378:metabolism; D051381:Rats; D013997:Time Factors; D000637:Transaminases / Q000378:metabolism; D014444:Tyrosine Transaminase / Q000378:metabolism
chemical_list: D000596:Amino Acids; D007651:Keto Acids; D011773:Pyruvates; D010649:Phenylalanine; D005934:Glucagon; D010651:Phenylalanine Hydroxylase; D000637:Transaminases; D014444:Tyrosine Transaminase; C022341:phenylalanine (histidine) aminotransferase