Formation and fate of tyrosine. Intracellular partitioning of newly synthesized tyrosine in mammalian liver.
Tyrosine in an hepatocyte is transported from the plasma, synthesized from phenylalanine, or released during protein turnover. Effects of phenylalanine and tyrosine on the formation and fate (partitioning) of tyrosine from the different sources were examined in primary rat hepatocyte cultures. Rates of tyrosine degradation, transport, incorporation into and release from protein, and synthesis from phenylalanine were measured as well as the intracellular dilution of labeled tyrosine and phenylalanine incorporated into protein. We found tyrosine had little effect on phenylalanine hydroxylation over a wide range of conditions, that transported tyrosine and tyrosine from phenylalanine are in different metabolic pools, and that there appears to be channeling of newly synthesized tyrosine during degradation. In addition, under some conditions, intracellular partitioning of tyrosine is determined by tyrosine concentration. Specifically, if extracellular tyrosine is low and phenylalanine is at a normal plasma level, tyrosine use in protein synthesis takes precedence over tyrosine degradation or export. It is proposed that the mechanism controlling this is kinetic, based on relative rates of tyrosyl-tRNA formation and tyrosine degradation and export. A quantitative model of tyrosine and phenylalanine in-flow and out-flow in hepatocytes is given, incorporating tyrosine synthesis, degradation, plasma membrane transport, and tyrosine and phenylalanine use and release during protein turnover.
Shiman
R
R
Department of Biochemistry and Molecular Biology, The Pennsylvania State University College of Medicine, Hershey, Pennsylvania 17033, USA.rshiman@psu.edu
Gray
D W
DW
D000818:Animals; D001692:Biological Transport / Q000187:drug effects; D002451:Cell Compartmentation / Q000187:drug effects; D002478:Cells, Cultured; D016895:Culture Media, Serum-Free; D003907:Dexamethasone / Q000494:pharmacology; D005934:Glucagon / Q000494:pharmacology; D007328:Insulin / Q000494:pharmacology; D007700:Kinetics; D008099:Liver / Q000166:cytology / Q000378:metabolism*; D008297:Male; D008954:Models, Biological; D008956:Models, Chemical; D010649:Phenylalanine / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D014443:Tyrosine / Q000378:metabolism*; D014444:Tyrosine Transaminase / Q000032:analysis
D016895:Culture Media, Serum-Free; D007328:Insulin; D014443:Tyrosine; D010649:Phenylalanine; D003907:Dexamethasone; D005934:Glucagon; D014444:Tyrosine Transaminase