Metabolism of purines in cultured normal and HPRT-deficient human fibroblasts

Very low erythrocyte hypoxanthine phosphoribosyl transferase activity was found in a 6-month-old child with microcephaly, hyperuricemia, and retardation of central nervous development, who subsequently developed self-mutilation. Fibroblast cell extracts from this patient showed less than 6% of normal activity of HPRT. Major metabolic products of adenine-8-C¹⁴ by extracts from both the patient and normal subjects were identified by high-voltage electrophoresis and paper chromatography as adenosine 5-monophosphate, adenosine, and inosine. Inosine was the principal product of the fibroblast cell extracts from the first biopsy of the patient, whereas the normal fibroblast cell extracts produced predominantly adenosine. These results suggest that interconversion of the purine nucleotides plays a significant role in metabolism of these fibroblast cell extracts.This project received support from the M.R.C. grant MA-3331 and the Canadian Arthritis and Rheumatism Society.