The mechanism of Na+-dependent D-glucose transport.
The mechanism of Na+-dependent D-glucose transport was investigated by kinetic means in rabbit small intestinal and renal brush border membranes. The rate of glucose transport was measured under equilibrium exchange conditions as a function of its own concentration and of the Na+ concentration. Likewise, the rate of Na+ transport was measured as a function of the D-glucose concentration. Noteworthy characteristics of the Na+-dependent glucose transport system are: 1) linear dependence of the glucose transport rate on Na+ concentration up to 0.1 M (at constant ionic strength), indicating a 1:1 stoichiometry of Na+-D-glucose cotransport under net flux conditions; 2) virtual Na+ independence of the apparent affinity of the transport system for D-glucose; 3) a stimulation-inhibition pattern if the transport rate of either substrate (D-glucose, Na+) is measured as function of increasing concentrations of its co-substrate; 4) a varying flux ratio of D-glucose to Na+ which can be either above or below 1, depending on the concentration ratio of the two substrates; 5) a rate constant for translocation of the loaded carrier which is faster than that for the dissociation of Na+. Treating Na+-D glucose co-transport analogous to an enzyme reaction, these features are consistent with an iso-ordered-bi-bi kinetic model, whereby the first solute that binds to the transport system at one membrane interface is the one that is released first at the other interface (first-in-first-out characteristics). The kinetic model is explained by a gated pore mechanism, whereby the translocation of the transported solutes across the permeability barrier is achieved by a rocker-type conformational change of the transport system (presumed to be a protein) which moves the permeability barrier past the solutes.
D000818:Animals; D001693:Biological Transport, Active / Q000187:drug effects; D002462:Cell Membrane / Q000378:metabolism*; D005947:Glucose / Q000378:metabolism*; D007413:Intestinal Mucosa / Q000378:metabolism; D007421:Intestine, Small / Q000378:metabolism*; D007672:Kidney Cortex / Q000378:metabolism*; D007700:Kinetics; D008433:Mathematics; D008871:Microvilli / Q000378:metabolism*; D008954:Models, Biological; D010695:Phlorhizin / Q000494:pharmacology; D011817:Rabbits; D012964:Sodium / Q000494:pharmacology*
D012964:Sodium; D010695:Phlorhizin; D005947:Glucose