In vivo metabolism of deutero-L-phenylalanine and deutero-L-tyrosine in normal and in various tumor-bearing rats

Abstract

The hydroxylation rate and rate of tyrosine catabolism are measured by injection of ring-deuterated L-phenylalanine and ring-deuterated L-tyrosine and subsequent deuterium determination in the water fraction of the blood. The hydroxylation rate was confirmed as the rate-limiting step. Whereas tyrosine catabolism yields normal Michaelis-Menten kinetics, homotropic activation is demonstrated for the hydroxylation step. In all tumor rats under study, the rates of phenylalanine hydroxylation and tyrosine catabolism are decreased. The delta-values to control increase with tumor age. In tumor rats, the hydroxylation step remains the rate-limiting one. Kinetic data indicate that the decrease in hydroxylation is due to a decreased turnover rate of the enzyme, whereas the increase in tyrosine catabolism is caused by the branching off of tyrosine or an intermediate on the route to D2O formation. The results are discussed with respect to altered levels of tetrahydrobiopterin, phenylalanine and tyrosine found during parallel investigations.