Transport of Folic Acid and Related Compounds Across the Small Intestine

Abstract

The intestinal transport of folic acid (pteroyl-L-glutamic acid) was investigated using in vitro preparations of rat jejunum. It was established that folic acid is accumulated in the gut wall and transported into the serosal compartment by a saturable mechanism. The kinetic parameters and the temperature dependence of the process were calculated, and it was shown that the transport mechanism had a limited dependence on aerobic metabolism. When the folic acid derivative 10-formylfolic acid was present in the incubation medium at a 10:1 molar ratio with labelled folic acid the tissue accumulation was significantly reduced though the serosal transfer was not significantly changed. It was also shown that the efflux of pre-loaded folic acid from the gut wall was stimulated in the presence of a high mucosal concentration of pteroyl­ L-glutamic acid, 10-formylfolic acid and methotrexate. Pteroyl-D-glutamic acid had a less significant effect, and pteroic acid produced no displacement. Folic acid was not present at a high concentration, in free solution, within the gut wall after a loading incubation, and it was concluded that the stimulated efflux arose as the result of displacement of labelled folic acid from binding sites within the tissue. It was shown that the displacement phenomenon was localised in the proximal region of the small intestine. The uptake of folic acid by a preparation of isolated jejuna! mucosal cells was studied, together with some aspects of their morphology. The interpretation of these results is discussed at some length in the light of the previous literature, and having regard to the known physico-chemical properties of folic acid. A mechanism for folate absorption is proposed in which absorption occurs by passive, non-ionic diffusion. It is suggested that the uptake of folic acid is enhanced in the jejunum by a "microclimate" at the mucosa! surface having a pH more acidic than the bulk luminal phase.