Vol. 58, Issue 4, 738-746, October 2000

Organic Vanadium Chelators Potentiate Vanadium-Evoked Glucose Metabolism In Vitro and In Vivo: Establishing Criteria for Optimal Chelators

Itzhak Goldwaser, Sun Qian, Eytan Gershonov, Mati Fridkin, and Yoram Shechter

Departments of Biological Chemistry (I.G., S.Q., Y.S.) and Organic Chemistry (I.G., E.G., M.F.), The Weizmann Institute of Science, Rehovot, Israel

Several ligands, when complexed with vanadium, potentiate its insulinomimetic activity both in vivo and in vitro. We have recently found that L-Glu--monohydroxamate (HXM) and L-Asp()HXM were especially potent in this regard. In the present study, we used vanadium-enriched adipose cells and cell-free experimental systems to determine the features of L-Glu()HXM and L-Asp()HXM that turn these ligands into optimal-synergizing vanadium chelators. We found that L-Glu()HXM and L-Asp()(HXM) possess the following characteristics: 1) They associate with vanadium(+5) at pH 7.2 within a narrow range of an apparent formation constant of 1.3 to 1.9 × 10² M¹; 2) they have nearly the same binding affinity for the vanadyl(+4) cation and the vanadate(+5) anion at physiological pH values; and 3) they form intense ultraviolet absorbing complexes upon associating with vanadium(+4) at 1 and 3 M stoichiometry, respectively, at pH 3.0. Vanadium ligands lacking any of these three defined criteria synergize less effectively with vanadium to activate glucose metabolism.