The chemical and steric determinants governing sugar interactions with renal tubular membranes

Abstract

Abstract 1. 1. The multiple indicator dilution technique in vivo has been used to study the specificity of interaction of pyranoside derivatives with renal tubular surfaces in dog kidney. The substances used include [ 14 C]-methyl-α- d -glucose, [ 3 H] methyl-β- d -glucoside, d -[ 14 C]mannosamine, d -[ 14 C]fructose, l -[6- 14 C]iodose, d -[ 3 H]-allose, [2- 3 H] myo -inositol, [ 14 C]glucosamine-HCl and d -[6- 3 H]mannosamine hydrochloride. 2. 2. For the luminal (brush border) membrane the specificity characteristics consist of: (i) a pyranose ring in a chair conformation (ii) OH groups on carbons 3 and 6 oriented as in configuration of d -glucose. 3. 3. For the antiluminal membrane the specificity characteristics are (i) a pyranose ring in a chair conformation (ii) hydroxyl groups on carbons 1 and 2 (iii) OH groups if present on carbons 3 and 6 should be oriented equatorially as in the configurations of d -glucose. 4. 4. These data are compatible with the specificity of inhibition of high affinity phlorizin receptors in vitro, and suggest that these receptors are identical to the sites associated with the glucose-transport mechanism. 5. 5. The results also suggest that the dominant feature controlling the dynamics of the interaction between sugars and membrane-bound transport receptors is the position of certain functional hydroxyl groups relative to the plane of the pyranose chair (Cl or 1C), defined by carbons 2, 3, 5, and the ring oxygen. In this regard the axial orientation of a single OH group on the pyranoside may be of special importance to the sugar-receptor interaction.