Purine-Nucleoside Phosphorylase and Adenosine Aminohydrolase Activities in Fibroblasts with the Leschnyhan Mutation

Abstract

The Lesch-Nyhan syndrome is an X-linked disease (Lesch, Nyhan, 1964) characterized by a nearly total deficiency of the hypoxanthine-guanine phosphoribosyltransferase activity in several tissues including the fibroblasts (Seegmiller et al., 1967; Rosenbloom et al., 1967, 1968). The de novo synthesis of purine nucleotides is greatly enhanced, and the levels of hypoxanthine and xanthine are considerably increased (Rosenbloom et al., 1967; Balis et al., 1967). It has been postulated (Lee et al., 1973) that there is some coordinate control of the activities of the enzymes participating in the purine metabolic pathway; this control is suggested to be related to the levels of the intermediate metabolites. Barankiewicz et al. (1975) have found that in the mammary glands of mice the direction of changes in hypoxanthine-guanine phosphoribosyltransferase and purine-nucleoside phosphorylase activities was the same for both enzymes, i.e. they both either increased or dropped at the same time. Therefore, it was of interest to determine whether the activities of purine-nucleoside phosphorylase and adenosine aminohydrolase in the fibroblasts lacking hypoxanthine-guanine phosphoribosyltransferase are altered.