Conformational Specificity in a Biological Sugar Transport System

The ‘carrier’ system in the surface of the human erythrocyte, facilitating passage of monosaccharides through the cell membrane, reacts preferentially with those sugars in which the pyranose ring tends to assume the particular ‘chair’ shape designated by Reeves as the ‘C1’ conformation. This novel type of steric specificity was revealed in a comparative study of fourteen aldoses (6 pentoses, 5 hexoses, and 3 deoxyhexoses), in which the dissociation constants of the carrier-sugar complexes were derived from the kinetics of the transfer process and of the competitive inhibition by phloretin. The sequence of increasing affinities thus determined paralleled the sequence of increasing relative stability in the C1 conformation as dictated by the distribution of substituent groups between axial and equatorial positions on the ring. Sugars predominantly stable in the other chair conformation (1C) showed extremely low affinity. Since no instance of biological utilization of the latter sugars has apparently yet been found, it is suggested that the necessity for the C1 ring-shape is basic in all enzymic reactions with pyranoses. However, most systems show further special requirements for particular side-group arrangements, which are superimposed on the primary ring specificity seen in the red cell's sugar transport system.