Folic acid transport in organ-cultured mucosa of human intestine. Evidence for distinct carriers.
The transport of folic acid was investigated in organ-cultured endoscopic biopsy specimens of intestinal mucosa from normal subjects. In the proximal small intestine at pH 5.5 and 6.5, [3H]folic acid accumulated to concentrations 2.64- and 2.17-fold higher than those of the medium, respectively, but at pH 7.5 the concentration was same as that of the medium. Saturability of initial rates of uptake was demonstrable with respect to luminal concentrations of [H+] and folic acid. Two proton-dependent transport mechanisms were evident: (a) a carrier with a low affinity for H+ and a low capacity for folic acid, and (b) a high-affinity, high-capacity carrier (Km, 635 and 54.6 nmol/L [H+]; Vmax, 0.066 and 2.583 pmol folic acid/microL intracellular water per 10 minutes, respectively). Kinetic studies of folic acid uptake at pH 5.5 and 7.5 revealed a difference in Km for folic acid (15.76 and 34.38 mumol/L, respectively) with no change in Vmax. In the colon, folic acid did not accumulate against a concentration gradient, and the initial rate of uptake was not affected by luminal pH. The accumulation of folic acid in colonic mucosa was significantly higher at pH 5.5 than at 7.5 and showed significant regional variation, with optimal uptake in the sigmoid colon. Methotrexate inhibited folic acid uptake competitively both in the proximal small intestine and in the cecum (inhibition constant 6.9 and 54 mumol/L, respectively, at pH 5.5). These data indicate the presence of a proton-dependent, active transport of folic acid in the proximal small intestine at pH 5.0-6.5. At pH 7.5 and in the mucosa of the colon, uptake of folic acid proceeds by facilitated diffusion through a low-affinity carrier.
Department of Gastroenterology, Hadassah University Hospital, Jerusalem, Israel.
J
J
Zimmerman
D001693:Biological Transport, Active / Q000502:physiology; D002352:Carrier Proteins / Q000378:metabolism*; D003470:Culture Media; D058973:Folate Receptors, GPI-Anchored; D005492:Folic Acid / Q000378:metabolism*; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007408:Intestinal Absorption / Q000502:physiology; D007413:Intestinal Mucosa / Q000378:metabolism*; D008727:Methotrexate / Q000494:pharmacology; D009924:Organ Culture Techniques / Q000379:methods; D011956:Receptors, Cell Surface
D002352:Carrier Proteins; D003470:Culture Media; D058973:Folate Receptors, GPI-Anchored; D011956:Receptors, Cell Surface; D005492:Folic Acid; D008727:Methotrexate