Folate transport by human intestinal brush-border membrane vesicles.
Transport of folic acid (Pte-Glu) across the brush-border membrane of human intestine was studied using brush-border membrane vesicle (BBMV) technique. The transport of Pte-Glu was higher in BBMV prepared from the jejunum than those prepared from the ileum (0.70 +/- 0.05 and 0.14 +/- 0.02 pmol X mg protein-1 X 10 s-1, respectively). The transport of Pte-Glu appeared to be carrier mediated and was pH dependent and increased with decreasing incubation buffer pH; saturable (Kt = 1.69 microM, Vmax = 4.72 pmol X mg protein-1 X 10 s-1); inhibited in a competitive manner by the structural analogues 5-methyltetrahydrofolate, methotrexate, and 5-formyltetrahydrofolate (Ki = 2.2, 1.4 and 1.4 microM, respectively); not affected by inducing a relatively positive or negative intravesicular compartment; independent of Na+ gradient; and inhibited by 4,4'-diisothiocyanatostlibene-2,2'-disulfonic acid (DIDS), an anion exchange inhibitor. The increase in Pte-Glu transport on decreasing incubation buffer pH appeared to be in part mediated through a direct effect of acidic pH on the transport carrier and in part through the pH gradient imposed by activating Pte-Glu-:OH- exchange and/or Pte-Glu-:H+ co-transport mechanisms. The important role of an acidic extravesicular environment in Pte-Glu transport is consistent with a role for the intestinal surface acid microclimate in folate transport. These results demonstrate that Pte-Glu transport in human BBMV occurs by a carrier-mediated system that is similar to that described for rat and rabbit intestinal BBMV.
D017878:4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid; D012856:4-Acetamido-4'-isothiocyanatostilbene-2,2'-disulfonic Acid / Q000031:analogs & derivatives / Q000494:pharmacology; D001692:Biological Transport / Q000187:drug effects; D005492:Folic Acid / Q000031:analogs & derivatives / Q000378:metabolism*; D005493:Folic Acid Antagonists / Q000494:pharmacology; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007082:Ileum / Q000648:ultrastructure; D007422:Intestines / Q000648:ultrastructure*; D007425:Intracellular Membranes / Q000378:metabolism; D007583:Jejunum / Q000648:ultrastructure; D008297:Male; D008564:Membrane Potentials; D008871:Microvilli / Q000378:metabolism*; D008875:Middle Aged; D009994:Osmolar Concentration; D012964:Sodium / Q000494:pharmacology
D005493:Folic Acid Antagonists; D012856:4-Acetamido-4'-isothiocyanatostilbene-2,2'-disulfonic Acid; D005492:Folic Acid; D012964:Sodium; D017878:4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid