title: Organic vanadium chelators potentiate vanadium-evoked glucose metabolism in vitro and in vivo: establishing criteria for optimal chelators.
abstract: Several ligands, when complexed with vanadium, potentiate its insulinomimetic activity both in vivo and in vitro. We have recently found that L-Glu-gamma-monohydroxamate (HXM) and L-Asp(beta)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(gamma)HXM and L-Asp(beta)HXM that turn these ligands into optimal-synergizing vanadium chelators. We found that L-Glu(gamma)HXM and L-Asp(beta)(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 x 10(2) 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.
authors.affiliation: Department of Biological Chemistry, The Weizmann Institute of Science, Rehovot, Israel.
authors.forename: I
authors.initials: I
authors.lastname: Goldwaser
authors.forename: S
authors.initials: S
authors.lastname: Qian
authors.forename: E
authors.initials: E
authors.lastname: Gershonov
authors.forename: M
authors.initials: M
authors.lastname: Fridkin
authors.forename: Y
authors.initials: Y
authors.lastname: Shechter
mesh_terms: D017667:Adipocytes / Q000187:drug effects* / Q000378:metabolism; D000818:Animals; D002474:Cell-Free System; D004357:Drug Synergism; D004578:Electron Spin Resonance Spectroscopy; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005947:Glucose / Q000378:metabolism*; D005971:Glutamates / Q000494:pharmacology*; D006863:Hydrogen-Ion Concentration; D006877:Hydroxamic Acids / Q000494:pharmacology*; D066298:In Vitro Techniques; D008024:Ligands; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D012441:Saccharomyces cerevisiae / Q000187:drug effects; D014639:Vanadium / Q000494:pharmacology*
chemical_list: D004791:Enzyme Inhibitors; D005971:Glutamates; D006877:Hydroxamic Acids; D008024:Ligands; D014639:Vanadium; C050614:glutamate-gamma-hydroxamic acid; D005947:Glucose