A model for the mode of action of cytochalasin B inhibition of D-glucose transport in the human erythrocyte.

Abstract

By an optical method, cytochalasin B is shown to be a competitive inhibitor of D-glucose transport across the human erythrocyte membrane with Ki of 1.2 x 10(-7) M. A Drieding molecular model of cytochalasin B reveals an almost identical spatial distribution of four oxygen atoms to those found in the C1-conformation of beta-D-glucopyranose and implicated in hydrogen bonding to the carrier protein associated with D-glucose transport. The stereochemistry of this transport model is discussed. On the basis of the interoxygen distances found in cytochalasin B, hydrocortisone, prednisolone, corticosterone, and phenolphthalein are considered as analogues and are shown to be competitive inhibitors of D-glucose transport with Ki values of 2.2 x 10(-4) M, 3.0 x 10(-4) M, 4.0 x 10(-4) M, and 2.5 x 10(-5) M, respectively. These results are considered to be consistent with the proposed mode of action of cytochalasin B and also provide further support for the model of D-glucose stereospecifically hydrogen-bonded to a carrier protein.