STUDIES ON THE FUNCTION OF VITAMIN A IN METABOLISM

Abstract

Vitamin A, one of the earliest vitamins to be discovered, has so far eluded attempts to uncover its function in metabolism.Its role in vision, brilliantly elucidated by Wald and his group, though important, cannot be its only function, since an animal dies from vitamin A deficiency but not necessarily from blindness.A great deal of effort and research has been expended in the field of the morphological changes caused by a deficiency of the vitamin, such as epithelial keratinization.However, this work has not led to any clues concerning the changes occurring on the molecular level, and indeed the observed morphological lesions may be only the final and distant manifestations of an originally molecular lesion.Comparatively little is known about the metabolic effects of vitamin A deficiency, Oxygen uptake in.vitro was shown to be lowered somewhat in vitamin A deficiency (1).Total carcass fat was found to be decreased in vitamin A-deficient rats compared to that of pair-fed rats (2) ; cholesterol levels were shown to be unaffected (3).Rather than study the change in level of a particular metabolite, a more dynamic approach to the problem was sought in the present work.The level of incorporation of radioactivity from administered radioactive substrates into the members of a known chain of intermediary metabolites was determined in order to discover a possible block caused by the vitamin deficiency.In this way, the enzymatic step requiring the vitamin may be located.Ideally, in a reaction sequence A 4 B -+ C -+ D, if a vitamin is required for step B + C, then, starting with radioactive A, in deficiency, radioactivity will appear in B, but not in C and D. Starting with radioactive B, no radioactivity will appear in C and D, but with radioactive C radioactivity will appear in D, in spite of the deficiency.