CADMIUM INCREASES GLUT1 SUBSTRATE-BINDING AFFINITY IN-VITRO WHILE REDUCING ITS CYTOCHALASIN-B BINDING-AFFINITY

Cadmium stimulates glucose transport in fibroblasts, apparently by inc reasing the intrinsic activity of GLUT1 [Harrison, S. A., Burton, J. M ., Clancy, B. M., & Czech, M. P. (1991) J. Biol. Chem. 266, 19438-1944 9]. In the present study, we examined whether cadmium affects the bind ing in vitro of purified GLUT1 to glucose and cytochalasin B. Cadmium inhibited cytochalasin B binding to GLUT1 competitively by reducing it s binding affinity with an apparent inhibition constant of approximate ly 0.2 mM. However, D-glucose displaced cytochalasin B bound to GLUT1 as effectively in the presence of cadmium as in its absence, and detai led analysis of this displacement revealed that cadmium in fact increa ses the substrate binding affinity significantly. These findings sugge st that cadmium induces a specific conformational change in GLUT1 that interferes with cytochalasin B binding but enhances substrate binding , This is the first clear demonstration in which the substrate and cyt ochalasin B binding activities of GLUT1 are differentially affected, w hich may offer insight into the workings of the glucose transporter.