An alternate metabolic route for the synthesis of inosine 5'-phosphate (IMP) in the Lesch-Nyhan erythrocyte.

Abstract

The cells of the Lesch-Nyhan individual, which are deficient in hypoxanthine-guanine phosphoribosyltransferase (HGPRT) activity, lack the ability to convert the 6-keto purines, hypoxanthine and guanine, to the corresponding nucleotides (1). Mammalian cells, in general, lack appreciable kinase activity for the 6-keto purine nucleosides, inosine and guanosine (2,3). Thus, the major route to IMP and GMP in the Lesch- Nyhan cell is via the overall pathway of de novo purine nucleotide synthesis in which the purine ring of IMP is built up on carbon 1 of a molecule of ribose 5-phosphate (4), The IMP is readily converted to GMP in normal human and Lesch-Nyhan cells.