Vincent J B
Department of Chemistry and Coalition for Biomolecular Products, The University of Alabama Tuscaloosa, 35487-0336, USA.
J Am Coll Nutr. 1999 Feb;18(1):6-12. doi: 10.1080/07315724.1999.10718821.
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.
长期以来，人们已知铬对于哺乳动物正常的脂质和碳水化合物代谢至关重要，铬缺乏会导致与成人发病型糖尿病和心血管疾病相关的症状。然而，阐明铬的生物活性形式的结构、功能和作用方式一直是个谜。不过，在我们实验室中发现了一种天然存在的寡肽，即低分子量铬结合物质（LMWCr），在存在100纳摩尔胰岛素的情况下，它能将胰岛素受体激酶活性激活高达7倍，解离常数为250皮摩尔，并且已经对其结构和光谱性质进行了部分表征。LMWCr的作用方式可能类似于钙结合信号蛋白钙调蛋白。换句话说，LMWCr以其活性脱辅基寡肽形式存在；响应铬通量时，LMWCr会结合4个铬离子。然后全蛋白能够与胰岛素受体（也许还有其他酶）结合，激活该酶。在营养物质铬、LMWCr对胰岛素受体激酶活性的激活以及成人发病型糖尿病和相关病症之间建立联系，可能会为这些病症带来新的治疗方法。
