title: Altered purine and pyrimidine metabolism in erythrocytes with purine nucleoside phosphorylase deficiency.
abstract: Purine and pyrimidine metabolism was compared in erythrocytes from three patients from two families with purine nucleoside phosphorylase deficiency and T-cell immunodeficiency, one heterozygote subject for this enzyme deficiency, one patient with a complete deficiency of hypoxanthine-guanine phosphoribosyltransferase, and two normal subjects. The erythrocytes from the heterozygote subject were indistinguishable from the normal erythrocytes. The purine nucleoside phosphorylase deficient erythrocytes had a block in the conversion of inosine to hypoxanthine. The erythrocytes with 0.07% of normal purine nucleoside phosphorylase activity resembled erythrocytes with hypoxanthine-guanine phosphoribosyltransferase deficiency by having an elevated intracellular concentration of PP-ribose-P, increased synthesis of PP-ribose-P, and an elevated rate of carbon dioxide release from orotic acid during its conversion to UMP. Two hypotheses to account for the associated immunodeficiency--that the enzyme deficiency leads to a block of PP-ribose-P synthesis or inhibition of pyrimidine synthesis--could not be supported by observations in erythrocytes from both enzyme-deficient families.
mesh_terms: D002648:Child; D002675:Child, Preschool; D003853:Deoxyribonucleosides / Q000494:pharmacology; D004912:Erythrocytes / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism*; D006801:Humans; D007041:Hypoxanthine Phosphoribosyltransferase / Q000172:deficiency; D007153:Immunologic Deficiency Syndromes / Q000209:etiology / Q000378:metabolism; D007926:Lesch-Nyhan Syndrome / Q000378:metabolism; D008297:Male; D010430:Pentosyltransferases / Q000172:deficiency*; D010754:Phosphoribosyl Pyrophosphate / Q000096:biosynthesis; D011683:Purine-Nucleoside Phosphorylase / Q000172:deficiency*; D011687:Purines / Q000378:metabolism*; D011743:Pyrimidines / Q000378:metabolism*
chemical_list: D003853:Deoxyribonucleosides; D011687:Purines; D011743:Pyrimidines; D010754:Phosphoribosyl Pyrophosphate; D010430:Pentosyltransferases; D011683:Purine-Nucleoside Phosphorylase; D007041:Hypoxanthine Phosphoribosyltransferase