In vivo inhibition of rat liver phenylalanine hydroxylase by p-chlorophenylalanine and esculin : Experimental model of phenylketonuria

Abstract

The effect of p-chlorophenylalanine ( p-CPA) and esculin on the rat liver phenylalanine hydroxylase activity have been investigated. Results have demonstrated that both compounds are good inhibitors of the enzyme in vivo, the p-CPA being the strongest, and that esculin reinforces the inhibition produced by the former when both are administered together. l-Phenylalanine administration to rats treated with p-CPA plus esculin results in an enhancement of the levels of liver phenylalanine and its metabolites, which reach values similar to those found in tissues of phenylketonuric patients while tyrosine concentrations remain near the control values. All these results suggest that the use of the p-CPA plus esculin combination supplies an improved experimental model of phenylketonuria, which can be useful for biochemical studies.