A pH-dependent, carrier-mediated system for transport of 5-methyltetrahydrofolate in rat jejunum.
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 two systems: 1) an active, carrier-mediated system which is demonstrable at low concentrations; and 2) a diffusion system which is demonstrable at high concentrations. The active system is characterized by: 1) saturation kinetics with Km congruent to 0.3 microM; 2) accumulation against a concentration gradient with a serosal-to-mucosal ratio of 1.8; 3) inhibition by metabolic poisons; 4) inhibition by oxidized and reduced folate analogs; 5) temperature dependence; 6) sodium dependence; 7) glucose dependence; and 8) 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: 1) linear increase in the mucosal-to-serosal transport of 5-methyltetrahydrofolate with increasing mucosal concentration to 10(-6) M and above; 2) energy independence; 3) pH independence; and 4) 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.
D000818:Animals; D001693:Biological Transport, Active / Q000187:drug effects; D004058:Diffusion; D004305:Dose-Response Relationship, Drug; D005947:Glucose / Q000494:pharmacology; D006863:Hydrogen-Ion Concentration; D007583:Jejunum / Q000378:metabolism*; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D012964:Sodium / Q000494:pharmacology; D013696:Temperature; D013763:Tetrahydrofolates / Q000378:metabolism*
D013763:Tetrahydrofolates; D012964:Sodium; D005947:Glucose; C005984:5-methyltetrahydrofolate