TY - JOUR T1 - Organic Vanadium Chelators Potentiate Vanadium-Evoked Glucose Metabolism In Vitro and In Vivo: Establishing Criteria for Optimal Chelators JF - Molecular Pharmacology JO - Mol Pharmacol SP - 738 LP - 746 DO - 10.1124/mol.58.4.738 VL - 58 IS - 4 AU - Itzhak Goldwaser AU - Sun Qian AU - Eytan Gershonov AU - Mati Fridkin AU - Yoram Shechter Y1 - 2000/10/01 UR - http://molpharm.aspetjournals.org/content/58/4/738.abstract N2 - Several ligands, when complexed with vanadium, potentiate its insulinomimetic activity both in vivo and in vitro. We have recently found that l-Glu-γ-monohydroxamate (HXM) andl-Asp(β)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 ofl-Glu(γ)HXM and l-Asp(β)HXM that turn these ligands into optimal-synergizing vanadium chelators. We found thatl-Glu(γ)HXM and l-Asp(β)(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 M−1; 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. ER -