Studies on the possible mechanism of inactivation of phenylalanine hydroxylase bydestructive oxygen species

The enzymic hydroxylation of phenylalanine by phenylalanine hydroxylase (E.C. 1.14.16.1.) in vitro is dependenton the presence of hydrogen peroxide removing processes. The loss of phenylalanine hydroxylase activity can be preventedto the same extent by catalase as well as the presence of optimized amounts of both peroxidase and superoxide dismutase.Peroxidase alone exhibited only two third of the maximal protective effect of catalase whereas superoxide dismutase alone was not able to exert any protective influence on phenylalanine hydroxylase. These findings suggest that the termination of phenylalanine hydroxylation in the absence of hydrogen peroxide removing reactions is probably due to destructive oxygen species generated at the active site iron of phenylalanine hydroxylase in the presence of H₂O₂ and the tetrahydropterin cofactor.