THE BIOCHEMICAL BASIS OF COBALAMIN DEFICIENCY

Objective: In this report, our goal was to summarize the current knowl edge of the biochemical basis for the impaired DNA synthesis and neuro pathy associated with vitamin B-12 deficiency. Material and Methods: W e reviewed the pertinent literature and our clinical experience with c obalamin deficiency. Results: Studies have established that the megalo blastic blastic hematopoiesis associated with vitamin B-12 and folate deficiency is secondary to impaired DNA synthesis. Two mechanisms of i mpairment of DNA,synthesis have been proposed: the ''methylfolate trap hypothesis'' and the ''formate starvation hypothesis.'' One possibili ty is that both hypotheses may be contributory-that is, incoming dieta ry folate may be inaccessible for polyglutamation in accordance with t he methylfolate trap hypothesis, whereas the formate starvation hypoth esis may explain the failure to se already polyglutamated forms of fol ate. Conclusion: Although the pathophysiologic mechanisms of vitamin B -12 and folate deficiency are not completely understood, nutritional a nemias offer suitable models for the study of the biochemical basis of disease.