Altered erythrocyte pyrimidine activity in vitamin B12 or folate deficiency.
The net activity of orotidylic pyrophosphorylase and decarboxylase, sequential enzymes which catalyse the formation of uridine monophosphate from orotic acid in de novo pyrimidine biosynthesis, has been evaluated in erythrocytes of patients with folate or cobalamin deficiency. In patients with normoblastic haemopoiesis and normal cobalamin and folate status a direct relationship exists between the maturity of the peripheral blood erythrocyte population, as indicated by G6PD activity, and net orotidylic activity. In contrast in cobalamin or folate deficiency this co-ordinate relationship is not observed and net orotidylic activity is relatively reduced. Fractionation of erythrocytes by centrifugation demonstrates that this inordinately low orotidylic activity consistently occurs in the young erythrocyte population and is reversed by specific replacement therapy. In vitamin B12 or folate deficiency an impressive array of evidence now exists to implicate altered folate metabolism for the observed alterations in purine and pyrimidine metabolism (Das & Herbert, 1976). Of these changes the cornerstone defect resulting in megaloblastic maturation is impaired methylation of deoxyuridine monophosphate to thymidine monophosphate (Hoffbrand et al, 1976). In this context the reduced serum uridine plus uracil levels in patients with vitamin B12 deficiency (Parry & Blackmore, 1976) and the haematological response of these patients to orotic acid therapy (Rundles & Brewer, 1958) are not readily explicable. Since the conversion of orotic acid to uridine monophosphate depends on the integrity of the coupled activities of orotidylic pyrophosphorylase and decarboxylase, this study has quantitated this capacity in peripheral blood erythrocytes in patients with vitamin B12 or folate deficiency.
D004912:Erythrocytes / Q000201:enzymology / Q000378:metabolism*; D005260:Female; D005494:Folic Acid Deficiency / Q000097:blood* / Q000201:enzymology; D005954:Glucosephosphate Dehydrogenase / Q000097:blood; D006801:Humans; D008297:Male; D009962:Orotate Phosphoribosyltransferase / Q000097:blood; D009964:Orotidine-5'-Phosphate Decarboxylase / Q000097:blood; D011743:Pyrimidines / Q000097:blood*; D014805:Vitamin B 12 / Q000627:therapeutic use; D014806:Vitamin B 12 Deficiency / Q000097:blood* / Q000188:drug therapy / Q000201:enzymology
D011743:Pyrimidines; D005954:Glucosephosphate Dehydrogenase; D009962:Orotate Phosphoribosyltransferase; D009964:Orotidine-5'-Phosphate Decarboxylase; D014805:Vitamin B 12