Absorption and malabsorption of folates

Abstract

Folic acid is one of the 'younger' vitamins, yet it has attracted intensive study in the thirty years since the identification of pteroylglutamic acid and its polyglutamyl conjugates. The absorption and malabsorption of folates, natural, purified and synthetic, in disease has been studied more than any other vitamin and indeed folate absorption has become one clinical test of intestinal function. We know little about the release of folate from protein complexes, but we have learned, with the help of synthetic radiolabelled pteroylpolyglutamates that polyglutamyl folates are hydrolysed at or near the luminal border of the intestine and the released folate is efficiently absorbed. The rate limiting stage of folate absorption appears to be the transport of the monoglutamyl folate. In disease, and with drugs, folate malabsorption occurs primarily when monoglutamyl transport is depressed. The specific components of the folate transport system, listed in Table 4, are receiving increased attention. The mechanism of uptake is still a topic of controversy but a dual system including both a saturable and a diffusion component would explain most of the data. Reduction and methyl or formyl addition occur in the intestine but such metabolism is not obligatory for transport. The nature of folate binding within the cell and the function of specific folate binding proteins requires further study. At present we have little or no information about the mechanism of folate release from the epithelial cell to the circulation but this step also could influence the rate and specificity of overall process. The tools are now at hand to complete our understanding of the steps in folate absorption and metabolism. Such an understanding should facilitate the management of folate deficiency whenever it complicates gastrointestinal disease or drug therapy.