title: Control of phenylalanine and tyrosine metabolism by phosphorylation mechanisms.
abstract: A system for the parallel determination of enzyme phosphorylation and expressed activity in rat liver cells, and its application to studies of phenylalanine hydroxylase and tyrosine aminotransferase, is described. Phenylalanine hydroxylase is phosphorylated by agents which stimulate cyclic AMP- and Ca2+-dependent protein kinase activity. The phosphorylation site(s) appear to be the same for both kinases. Phosphorylation is accompanied by increased metabolic flux at low, physiologically relevant, substrate concentrations. Insulin and spermine both inhibit the phosphorylation of the enzyme, possibly by increasing dephosphorylation. Tyrosine aminotransferase is phosphorylated in liver cell incubations but the rate is slow and insensitive to additions to the medium. No parallel changes in flux could be detected. Both enzymes are subject to complex regulatory mechanisms, short- and long-term. Their activities may be coordinated in vivo by control exerted at the level of the plasma membrane where both amino acids share the same transport processes. Determination of the control coefficients for the several components indicates that membrane transport may be a major limitation on flux.
mesh_terms: D000818:Animals; D005934:Glucagon / Q000494:pharmacology; D066298:In Vitro Techniques; D007328:Insulin / Q000494:pharmacology; D008099:Liver / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D010649:Phenylalanine / Q000378:metabolism*; D010651:Phenylalanine Hydroxylase / Q000378:metabolism; D010766:Phosphorylation; D051381:Rats; D011919:Rats, Inbred Strains; D013096:Spermine / Q000494:pharmacology; D013566:Sympathomimetics / Q000494:pharmacology; D014443:Tyrosine / Q000378:metabolism*; D014667:Vasopressins / Q000494:pharmacology
chemical_list: D007328:Insulin; D013566:Sympathomimetics; D014667:Vasopressins; D013096:Spermine; D014443:Tyrosine; D010649:Phenylalanine; D005934:Glucagon; D010651:Phenylalanine Hydroxylase