In vitro and animal studies show that vanadate and other Because most cellular components contain hydroxyl and/or vanadium compounds increase glucose transport activity and phosphate groups, vanadate reacts as shown in eq. 1, and 2 normalize glucose metabolism [1-5]. Furthermore, these with a variety of metabolites. For example, the reaction of insulin-mimetic compounds can be administered orally. Vana- vanadate with the 2'-hydroxyl group of the cofactor NAD date enhances the phosphoprotein formation which is attrib- generates an NADP analog, NADV (path b) [22]. NADV is uted to either the activation of protein kinases or inhibition an excellent cofactor for enzymes such as glucose-6-phos- of protein phosphatases. Despite the interest in document- phate dehydrogenase, 6-phosphogluconate dehydrogenase, ing the effects of vanadate on protein kinases, most reports and alcohol dehydrogenase [22]. The presence ofNADV have used indirect methods and studies with purified kinases could affect the levels of reducing equivalents in the cell, im- show weak, if any, interaction of vanadate with kinases as portant in maintaining a normal glucose metabolism. This a group of enzymes (reviewed in Refs. [6-8]). Vanadate type of mechanism is distinct from the vanadate-induced interacts potently with phosphatases and the inhibition is NADH oxidation by plasma membranes [23]. Organic attributed to a five-coordinate vanadate complex which vanadates have been shown to substitute for organic phos- mimics the transition state of the phosphate ester hydroly- phates in many of the enzymes related to glucose metabolism sis reaction (reviewed in Refs. [7,9]).
