SummaryActivities of phosphoribosyltransferase for hypoxanthine and adenine were investigated in erythrocytes and human tissues of fetuses and adults as well as in cultivated fibroblasts and amniotic fluid cells. Kinetic characteristics of these enzymes were also studied in patients with the Lesch-Nyhan syndrome and with partial deficiency for hypoxanthine phosphoribosyltransferase (HGPRTase), and their obligate heterozygotes. The affinity of HGPRTase for both substrates in partial deficiency decreased to 13 to 20% of normal and by a less degree in its heterozygotes (50 to 65% of normal). A slight decrease in the Kmfor phosphoribosylpyrophosphate was observed in the case of heterozygotes for the Lesch-Nyhan syndrome.Elevated erythrocytic adenine phosphoribosyltransferase (APRTase) activity was found in fetuses, patients with the Lesch-Nyhan syndrome or with partial deficiency, and in some heterozygotes as well. However, the Kmof APRTase for hypoxanthine in these subjects was the same as that in the normal adults. The HGPRTase activity in liver increased almost 4 times during the developmental period, whereas the APRTase activity remained approximately the same. In fetal liver, the APRTase activity was almost two times higher than the HGPRTase activity, whereas in fetal brain the HGPRTase activity was higher. The Kmof HGPRTase for hypoxanthine in cultivated cells and human tissues were similar to that in erythrocytes and leukocytes. On the other hand, the HGPRTase affinity for phosphoribosylpyrophosphate in these cells was considerably larger than in erythrocytes or in leukocytes.SpeculationAberration in active sites of hypoxanthine phosphoribosyltransferase may be one of the causes for the decrease in enzyme activity in patients with partial deficiency. Phosphoribosylpyrophosphate may stabilize adenine phosphoribosyltransferase but not affect the stability of hypoxanthine phosphoribosyltransferase. Residual activity is often observed in cultivated cells and liver of patients with the Leach-Nyhan syndrome but rarely in their erythrocytes. This may be either due to the lower affinity of erythrocytic enzyme for phosphoribosylpyrophosphate or to the existence of a quite different enzyme in erythrocytes and leukocytes to that in cultivated cells and liver.