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

Progress in the biology of myo-inositol hexakisphosphate (InsP(6)) 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 InsP(6) occurs as Mg-5(H2L), a neutral complex that exists thanks to a significant, but undefined, window of solubility displayed by solid Mg-5(H2L) center dot 22H(2)O (L is fully deprotonated InsP(6)). Here we complete the description of the InsP(6)-Mg2+-Ca2+ system, defining the solubilities of the Mg2+ and Ca2+ (Ca-5(H2L) - 16H(2)O) solids in terms of K-s0 = [M2+](5)[H2L10-], with pKs0 = 32.93 for M = Mg and pK(s0) = 39.3 for M =: Ca. The concentration of soluble Mg-5(H2L) at 37 degrees C and I = 0.15 M NaClO4 is limited to 49 mu M, yet InsP(6) in mammalian cells may reach 100 mu M. Any cytosolic/nuclear InsP(6) in excess of 49 mu M must be protein- or membrane-bound, or as solid Mg-5(H2L) center dot 22H(2)O, and any extracellular InsP(6) (e.g. in plasma) is surely protein-bound. (c) 2006 Elsevier Inc. All rights reserved.