The binding of trivalent chromium to low-molecular-weight chromium-bindingsubstance (LMWCr) and the transfer of chromium from transferrin and chromium picolinate to LMWCr

A recent model for the role of chromium in insulin signaling requires that the oligopeptide low-molecular-weight chromium-binding substance (LMWCr) ti ghtly bind four chromic ions before the oligopeptide obtains a conformation required for binding to the tyrosine kinase active site of the insulin rec eptor. To test this model, the chromium-binding constant of LMWCr was deter mined, and the ability of LMWCr to remove chromium from Cr-2-transferrin an d the nutritional supplement chromium picolinate, Cr(pic)(3), was examined. These results are consistent with the model of the mode of action of LMWCr ; a Hill study indicates the four chromic ions bind to apoLMWCr in a highly cooperative fashion (n=3.47) with a binding constant of 1.54 x 10(21). Chr omium is readily transferred from transferrin to apoLMWCr at near neutral p H. The results also suggest that reduction of the chromic center of Cr(pic) (3) may be required for the supplement to release chromium; thus, release o f chromium is related to a mechanism by which Cr(pic)(3) may generate hydro xyl radicals in cells.