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The behaviour of myo-inositol hexakisphosphate in the presence of magnesium(II) and calcium(II): Protein-free soluble InsP6 is limited to 49 μM under cytosolic/nuclear conditions

  • Nicolás Veiga
  • Julia Torres
  • Sixto Domínguez
  • Alfredo Mederos
  • Robin F. Irvine
  • Alvaro Díaz
  • Carlos Kremer
Publication Date
Nov 01, 2006
  • Biology


Progress in the biology of myo-inositol hexakisphosphate (InsP6) has been delayed by the lack of a quantitative description of its multiple interactions with divalent cations. Our recent initial description of these [J. Torres, S. Dominguez, M.F. Cerda, G. Obal, A. Mederos, R.F. Irvine, A. Diaz, C. Kremer, J. Inorg. Biochem. 99 (2005) 828–840] predicted that under cytosolic/nuclear conditions, protein-free soluble InsP6 occurs as Mg5(H2L), a neutral complex that exists thanks to a significant, but undefined, window of solubility displayed by solid Mg5(H2L) · 22H2O (L is fully deprotonated InsP6). Here we complete the description of the InsP6–Mg2+–Ca2+ system, defining the solubilities of the Mg2+ and Ca2+ (Ca5(H2L) · 16H2O) solids in terms of Ks0 = [M2+]5[H2L10−], with pKs0 = 32.93 for M = Mg and pKs0 = 39.3 for M = Ca. The concentration of soluble Mg5(H2L) at 37 °C and I = 0.15 M NaClO4 is limited to 49 μM, yet InsP6 in mammalian cells may reach 100 μM. Any cytosolic/nuclear InsP6 in excess of 49 μM must be protein- or membrane-bound, or as solid Mg5(H2L) · 22H2O, and any extracellular InsP6 (e.g. in plasma) is surely protein-bound.

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