Impaired utilization of serum folate in pernicious anemia

Abstract

The possible role of cobalamins in the utilization of serum methyltetrahydrofolate has been investigated by means of radiolabeled methyltetrahydrofolate in subjects suffering from pernicious anemia. After intravenous administration, methyltetrahydrofolate-³H (SA 11,500 Ci/mole; dose 0.05 μg/kg) was cleared from the serum to tissues of B₁₂-deficient subjects half as fast as after the same subjects had received vitamin B₁₂ therapy. B₁₂ deficiency was also associated with an increased rate of renal excretion of methyltetrahydrofolate or its derivatives, and a decreased rate of renal metabolism of methyltetrahydrofolate to other urinary folate derivatives. Intravenously administered methyl-¹⁴C-tetrahydrofolate-³H at a higher dose (5 μg/kg) caused a severalfold elevation of the total serum folate concentration and, in B₁₂-deficient subjects, it did not disappear from the serum significantly more slowly although its urinary excretion was significantly increased. These results indicate that there is some cobalamin requirement for the utilization of serum methyltetrahydrofolate and verify one prediction of the “methyltetrahydrofolate trap” explanation for the megaloblastosis of B₁₂ deficiency.