Na⁺-Dependent Transport of Carbohydrates through Intestinal Epithelium

Abstract

Several years ago, my colleagues and I presented a concept of the brush border membrane of the epithelial cell as a digestive-absorptive surface in which the elements responsible for digestion and absorption were postulated to be arranged in ordered proximity to one another (Crane, Miller and Bihler 1961, Crane 1962). The disaccharidases were represented as being an integral part of the outer protein coat of the membrane and the diffusion barrier to the entry of monosaccharides into the epithelial cells was assumed, in line with current concepts of membrane function, to be the lipid leaflet. As a consequence of experiments carried out under conditions of limited tissue energy supplies, we believed that the entry of sugars across the brush border membrane was identified as the primary site ofNa⁺ involvement in the overall process of active transport, and we interpreted our experiments to have “established the existence of a substrate-specific, Na⁺-dependent and energy-independent process mediating the rapid equilibration of sugars between the cells and the medium” (Bihler, Hawkins and Crane 1962). Interaction of glucose and its analogs with a specific binding site on a mobile carrier was ‘postulated to account for the specificity of the overall process (Crane 1960) and for the competitive nature of phlorizin inhibition (Alvarado and Crane 1962). Interaction of Na⁺ with a second specific binding site was also postulated, and it was concluded that binding of Na⁺ to this site was essential to the ability of the carrier to equilibrate sugar across the brush border membrane. Simultaneous movement of Na⁺ and sugar were assumed to occur as a direct consequence of these postulated interactions. As we have visualized it, the Na⁺-dependent sugar carrier system is, per se,capable only of equilibration; the asymmetry required to achieve uphill accumulation of sugar is attributed to the movement of Na⁺ into the cell down a gradient of concentration maintained by the operation of an outwardly-directed, energy-dependent Na⁺-pump present at a different locus in the same membrane. The position of the Na⁺-pump, however, is not of prime importance; it is essential only that the local internal Na⁺ concentration in the region of the equilibrating carrier be maintained low relative to the medium.