The biochemical basis of cobalamin deficiency.

OBJECTIVE: In this report, our goal was to summarize the current knowledge of the biochemical basis for the impaired DNA synthesis and neuropathy associated with vitamin B12 deficiency.

MATERIAL AND METHODS: We reviewed the pertinent literature and our clinical experience with cobalamin deficiency.

RESULTS: Studies have established that the megaloblastic hematopoiesis associated with vitamin B12 and folate deficiency is secondary to impaired DNA synthesis. Two mechanisms of impairment of DNA synthesis have been proposed: the "methylfolate trap hypothesis" and the "formate starvation hypothesis." One possibility is that both hypotheses may be contributory--that is, incoming dietary folate may be inaccessible for polyglutamation in accordance with the methylfolate trap hypothesis, whereas the formate starvation hypothesis may explain the failure to use already polyglutamated forms of folate.

CONCLUSION: Although the pathophysiologic mechanisms of vitamin B12 and folate deficiency are not completely understood, nutritional anemias offer suitable models for the study of the biochemical basis of disease.