Modulations of rat hepatic phenylalanine hydroxylase due to induced diabetes or high-protein diet

The tetrahydrobiopterin-dependent activity and apparent state of phosphorylation of rat hepatic phenylalanine hydroxylase is stimulated three days after induction of diabetes by the administration of streptozotocin. This response can be inhibited by concurrent treatment with insulin. Animals that are subjected to the diabetic state for five to seven days show an apparent increase in the amount of hydroxylase present. In addition, rats fed on a high-protein diet for one week have elevated tetrahydrobiopterin-dependent hydroxylase activity and an altered distribution of the multiple forms of this enzyme. These observations support the conclusion that rat hepatic phenylalanine hydroxylase can be modulated in vivo both by transient and sustained mechanisms that are responsive to an altered physiological status.