Mechanisms of chromium action: low-molecular-weight chromium-binding substance.

Chromium has long been known to be essential for proper lipid and carbohydrate metabolism in mammals, with chromium deficiency leading to symptoms associated with adult-onset diabetes and cardiovascular disease. Elucidating the structure, function, and mode of action of the biologically active form of chromium has proved enigmatic. However, a naturally-occurring oligopeptide, low-molecular-weight chromium-binding substance (LMWCr), has been found in our laboratory to activate insulin receptor kinase activity up to 7-fold with a dissociation constant of 250 picomolar in the presence of 100 nanomolar insulin, and it has been partially characterized in terms of structural and spectroscopic properties. LMWCr may function in a manner similar to that of the calcium-binding signal protein calmodulin. In other words, LMWCr is maintained in its active apo-oligopeptide form; in response to a chromium flux, LMWCr binds 4 chromic ions. The holoprotein is then capable of binding 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 conditions could result in a new treatment for these conditions.