The effect of folate analogues and vitamin B12 on provision of thymine nucleotides for DNA synthesis in megaloblastic anemia

作者: MR Taheri , RG Wickremasinghe , BF Jackson , AV Hoffbrand

DOI: 10.1182/BLOOD.V59.3.634.634

关键词: HydroxocobalaminBiosynthesisDNA synthesisVitamin B12Thymidylate synthaseBiochemistryMegaloblastic anemiaChemistryAnemiaInternal medicineEndocrinologyDeoxyuridine

摘要: The role of vitamin B12 in the folate dependent biosynthesis thymidine nucleotides is controversial. In an attempt to clarify this, three methods have been used assess relative efficacy (hydroxocobalamin) and various analogues titrated concentrations at correcting 'de novo' thymidylate synthesis by megaloblastic human marrow cells: (1) deoxyuridine (dU) suppression test which analyses reduction (3H)-thymidine labeling DNA unlabeled dU. Marrow cells were also labeled with (6-3H)-dU assessment (2) its incorporation into (3) accumulation (6-3H)-deoxyuridine monophosphate (3H-dUMP). gave similar results. both, N6-formyl tetrahydrofolate (formyl-FH4) was most effective agent anemia due or deficiency. Vitamin corrected lesion deficiency but not Tetrahydrofolate (FH4) folic acid folate, although both deficiencies they less than formyl-FH4. Methyl-FH4 These results confirm failure methyl-FH4 utilisation They suggest that if needed formylation FH4, this a minor provision correct coenzyme for compared major FH4 from methyl-FH4.

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