Hemolytic anemia in hereditary pyrimidine 5'-nucleotidase deficiency. II. Effect of pyrimidine nucleotides and their derivatives on glycolytic and pentose phosphate shunt enzyme activity.
We evaluated the glycolytic intermediate concentrations from the erythrocytes of a patient with hereditary pyrimidine 5'-nucleotidase (P5'N) deficiency. Conclusive evidence for a metabolic block was not found. We evaluated the effects of the pyrimidine (cytidine and uridine) tri- and diphosphate nucleotides (CTP, CDP, UTP, UDP) and the choline and ethanolamine derivatives of CDP (CDP-choline, CDP-ethanolamine) on the activities of key enzymes of the Embden-Meyerhof pathway. CTP and UTP inhibited fructose-6-phosphate competitively for phosphofructokinase and phosphoenolpyruvate competitively for pyruvate kinase. In both cases, the Ki of the pyrimidine nucleotide and Km of the glycolytic substrate were above their intraerythrocytic concentrations. CTP was a competitive inhibitor of ADP for pyruvate kinase with a Ki near its intraerythrocytic concentration. CDP-choline and CDP-ethanolamine had no effect on the activities of Embden-Meyerhof or pentose phosphate shunt enzymes. Thus, the nature of the hemolytic anemia in hereditary P5'N deficiency remains enigmatic.
D015720:5'-Nucleotidase; D000255:Adenosine Triphosphate / Q000494:pharmacology; D000745:Anemia, Hemolytic, Congenital / Q000188:drug therapy / Q000201:enzymology*; D001667:Binding, Competitive; D003570:Cytidine Triphosphate / Q000494:pharmacology; D004912:Erythrocytes / Q000187:drug effects / Q000201:enzymology; D005954:Glucosephosphate Dehydrogenase / Q000037:antagonists & inhibitors; D006019:Glycolysis / Q000187:drug effects*; D006801:Humans; D009708:Nucleotidases / Q000172:deficiency*; D010427:Pentose Phosphate Pathway / Q000187:drug effects*; D010732:Phosphofructokinase-1 / Q000037:antagonists & inhibitors; D010734:Phosphogluconate Dehydrogenase / Q000097:blood; D010735:Phosphoglycerate Kinase / Q000097:blood; D011742:Pyrimidine Nucleotides / Q000494:pharmacology*; D011770:Pyruvate Kinase / Q000037:antagonists & inhibitors; D014544:Uridine Triphosphate / Q000494:pharmacology
D011742:Pyrimidine Nucleotides; D003570:Cytidine Triphosphate; D000255:Adenosine Triphosphate; D010734:Phosphogluconate Dehydrogenase; D005954:Glucosephosphate Dehydrogenase; D010732:Phosphofructokinase-1; D011770:Pyruvate Kinase; D010735:Phosphoglycerate Kinase; D009708:Nucleotidases; D015720:5'-Nucleotidase; D014544:Uridine Triphosphate