Mechanism of pH-Modulated Transport of 5-Methyltetrahydrofolate in Rat Jejunal Everted Sacs

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Absorption and transport of 5-methyltetrahydrofolate, the dietary form of the vitamin after intestinal hydrolysis, was studied in rat everted small intestinal segments. The folate transport from the mucosal to the serosal compartment was pH dependent and optimal at experimental pH4.0, and the transport was only 40-50% of that level at the physiological pH of the gut, i.e., 6.5-7.0. The methyltetrahydrofolate transport to the serosal site was not linked with any cotransport with H⁺, but the optimum transport was dependent on the mucosal acidic pH of 4 irrespective of the serosal pH. Methyltetrahydrofolates were, however, bound to their mucosal cell receptor optimally at pH6.5. Addition of ATP at the mucosal site enhanced mucosal to serosal folate transport at pH6.5 of the gut. A role for an intestinal mucosal Mg⁺-ATPase in the hydrolysis of ATP and formation of an acidic microclimate were observed. Sodium azide, an inhibitor of Mg⁺-ATPase, hindered methyltetrahydrofolate transport at pH6.5 but not at pH4.0. The overall results suggest that 5-methyltetrahydrofolate is absorbed in the intestine by a passive process in an acid microclimate at pH4.0 generated by intestinal mucosal brush-border Mg⁺-ATPase.