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 phenylalanin e and tyrosine on the formation and fate (partitioning) of tyrosine from th e different sources were examined in primary rat hepatocyte cultures. Rates of tyrosine degradation, transport, incorporation into and release from pr otein, and synthesis from phenylalanine were measured as well as the intrac ellular dilution of labeled tyrosine and phenylalanine incorporated into pr otein. We found tyrosine had little effect on phenylalanine hydroxylation o ver 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 determin ed by tyrosine concentration. Specifically, if extracellular tyrosine is lo w and phenylalanine is at a normal plasma level, tyrosine use in protein sy nthesis takes precedence over tyrosine degradation or export. It is propose d that the mechanism controlling this is kinetic, based on relative rates o f tyrosyl-tRNA formation and tyrosine degradation and export. A quantitativ e model of tyrosine and phenylalanine in-flow and out-flow in hepatocytes i s given, incorporating tyrosine synthesis, degradation, plasma membrane tra nsport, and tyrosine and phenylalanine use and release during protein turno ver.