M. Lachaal et al., CADMIUM INCREASES GLUT1 SUBSTRATE-BINDING AFFINITY IN-VITRO WHILE REDUCING ITS CYTOCHALASIN-B BINDING-AFFINITY, Biochemistry, 35(47), 1996, pp. 14958-14962
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.