Relative Folate Deficiency of Erythrocytes in Pernicious Anemia and its Correction with Cyanocobalamin

1. A relationship has been observed between the serum and erythrocyte folate in normal subjects.

2. Patients with folate deficiency were more readily differentiated from normal subjects by determinations of serum folate activity than by determinations of erythrocyte folate activity.

3. In pernicious anemia in relapse, accumulation of serum folate and/or depletion of erythrocyte folate was observed in all patients, resulting in a disturbance of the normal relationship between the serum and erythrocyte folate activity. This altered relationship was corrected following the reticulocytosis induced by vitamin B₁₂ therapy.

4. Patients receiving amethopterin therapy appear to incorporate the folate antagonist into maturing erythroid cells, since the erythroid cells so formed showed anti-bacterial activity for several weeks following the administration of the antagonist.

5. Preliminary fractionation of folate co-enzymes in erythroid cells of a patient with pernicious anemia before and after therapy revealed no significant difference in the distribution of the co-enzymes induced by therapy. A significant proportion of the folate activity of the erythroid cells was found in a fraction eluted from the DEAE column by sodium hydroxide.

6. The data presented are consistent with a direct effect of vitamin B₁₂ on folate transport into the erythroblast.