A PH-DEPENDENT, CARRIER-MEDIATED SYSTEM FOR TRANSPORT OF 5-METHYLTETRAHYDROFOLATE IN RAT JEJUNUM

Abstract

The intestinal transport of the naturally occurring folate coenzyme, 5-methyltetrahydrofolate, was studied using everted sacs of rat jejunum. The study provides evidence that intestinal transport of 5-methyltetrahydrofolate is composed of 2 systems: an active, carrier-mediated system which is demonstrable at low concentrations; and a diffusion system which is demonstrable at high concentrations. The active system is characterized by the following: saturation kinetics with Km .simeq. 0.3 .mu.M: accumulation against a concentration gradient with a serosal-to-mucosal ratio of 1.8; inhibition by metabolic poisons; inhibition by oxidized and reduced folate analogs; temperature dependence; Na dependence; glucose dependence; and specificity for the jejunum. These features are strongly pH-dependent, and demonstration of active transport of 5-methyltetrahydrofolate requires a buffer pH of 6, glucose in the incubation medium and a substrate concentration of less than 10-6 M. The diffusion process is characterized by the following: linear increase in the mucosal-to-serosal transport of 5-methyltetrahydrofolate with increasing mucosal concentration to 10-6 M and above; energy independence; pH independence; and temperature independence. These studies clarify the mechanism of intestinal transport of 5-methyltetrahydrofolate, show the similarities to transport of other folate compounds and provide a unified concept of intestinal folate transport.