Inosinate pyrophosphorylase activity in immature blood cells in X-linked congenital hyperuricosuria.

Abstract

Radioautographic examination of the bone marrow of three patients with X-linked congenital hyperuricosuria (Lesch-Nyhan's disease), after incubation with radioactive hypoxanthine, revealed no labeling even in extremely immature blood cells. An adequacy of the cosubstrate, phosphoribosepyrophosphate, in these cells was demonstrated by the appearance of labeling following incubation with tritiated adenine. It is concluded that the enzyme IMP pyrophosphorylase (inosinate: pyrophosphate phosphoribosyltransferase E.C.2.4.2.8) is deficient in young blood cells as well as in peripheral blood elements. The possibility that the enzyme deficiency in the peripheral blood results from the rapid degradation of an unstable enzyme is thereby excluded. Absence of radioactive labeling of terminal cells—erythrocytes, granulocytes, and platelets—is attributed to an insufficiency of the cosubstrate, phosphoribosepyrophosphate.