Mechanisms of chromium action: Low-molecular-weight chromium-binding substance

Chromium has long been known to be-essential for proper lipid and carbohydr ate metabolism in mammals, with chromium deficiency leading to symptoms ass ociated with adult-onset diabetes and cardiovascular disease. Elucidating t he structure, function, and mode of action of the biologically active form of chromium has proved enigmatic. However, a naturally-occurring oligopepti de, low-molecular-weight chromium-binding substance (LMWCr), has been found in our laboratory to activate insulin receptor kinase activity up to 7-fol d with a dissociation constant of 250 picomolar in the presence of 100 nano molar insulin, and it has been partially characterized in terms of structur al and spectroscopic properties. LMWCr may function in a manner similar to that of-the calcium-binding signal protein calmodulin. In other words, LMWC r is maintained in its active apo-oligopeptide form; in response to a chrom ium flux, LMWCr binds 4 chromic ions. The holoprotein is then capable of bi nding to insulin receptor (and perhaps other enzymes) activating the enzyme . Establishing a link between the nutrient chromium, LMWCr's activation of insulin receptor kinase activity, and adult-onset diabetes and related cond itions could result in a new treatment for these conditions.