Erythrocyte adenine phosphoribosyltransferase in the Lesch Nyhan syndrome

Lesch Nyhan syndrome, a neurological disease found in children is associated with increased purine production. It is caused by an almost complete deficiency of the X linked enzyme, hypoxanthine guanine phosphoribosyltransferase. In dialyzed hemolysates from affected children, adenine phosphoribosyltransferase (APRT), a separate autosomally determined enzyme, exhibits increased activity and relative stability to thermal inactivation. APRT in the hemolysates of two children with Lesch Nyhan syndrome was studied. The enzyme was normally sensitive to destabilization against heat inactivation by adenine, but resistant to destabilization by hypoxanthine. Other properties of the enzyme, including K(m) for substrates, optimal magnesium concentration, electrophoretic mobility, pH profile, and sensitivity to inhibition and to stabilization by 5 phosphoribosyl 1 pyrophosphate against thermal inactivation, were normal. The mechanisms underlying the abnormalities of APRT in the dialyzed hemolysates are discussed.