Folate transport.

Although a matter of some controversy in the face of differing experimental systems employing a wide range of substrate concentrations and conditions, there is a growing consensus that monoglutamyl folates are taken up by the intestinal epithelial cell by a structure-specific and energy-mediated transport process coded-for genetically. This "carrier-mediated" transport system can be demonstrated in several mammalian species in vitro and can be shown to be the property of the intestinal microvillus membrane in studies of isolated membrane vesicles. The transport system is highly pH-dependent with an optimum slightly below pH 6 which is very close to the pH of the proximal small intestine. At or near optimal pH the folate transport system exhibits saturation kinetics, competition among different forms of monoglutamyl folates and methotrexate, counter transport, and sensitivity to metabolic inhibitors. This system is functional in the physiological range of folate concentration under 10 microM. At high concentrations of folate in the intestine which can be achieved by folate therapy, folate uptake by diffusion is demonstrable. This latter process predominates at pharmacologic concentrations of folate above 10 microM.