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

Abstract

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.

Synthesis and biological actions of diphosphoinositol phosphates (inositol pyrophosphates), regulators of cell homeostasis

“…In fact, many cellular total InsP 6 measurements revealed values below 50 μ m , but in other cells also higher total concentrations up to 100 μ m were found (Table 2), in particular when correcting for a cytosolic plus nuclear water content of only 70 % of the wet weight of cells (see references in Veiga et al , 2006 3 H] myo-inositol demonstrated that a fraction of InsP 6 comprising > 50 % of the total prelabeled amount is apparently soluble and rapidly released. A smaller fraction effusing slower is a clear indication of limited diffusion or scavenging, respectively, of part of the prelabeled InsP 6 (Stuart et al , 1994 ).…”

“…Inside cells (pH 7.0 -7.1), where resting Ca 2 + is below micromolar and cellular Mg 2 + is the prevailing free cation varying between 0.5 and 1.5 m m free concentration, according to the calculations of Kremer and coworkers (Veiga et al , 2006 ), a solubility window of the dominant hydrated (Mg) 5 H 2 InsP 6 complex of up to 49 μ m should exist. In fact, many cellular total InsP 6 measurements revealed values below 50 μ m , but in other cells also higher total concentrations up to 100 μ m were found (Table 2), in particular when correcting for a cytosolic plus nuclear water content of only 70 % of the wet weight of cells (see references in Veiga et al , 2006 3 H] myo-inositol demonstrated that a fraction of InsP 6 comprising > 50 % of the total prelabeled amount is apparently soluble and rapidly released.…”

Effect of phytic acid etchant on the structural stability of demineralized dentine and dentine bonding

“…1a) thus having the ability to chelate with minerals (multivalent cations), such as calcium. 23,24 More interestingly, IP6 can bind to some kinds of protein, forming direct and indirect complexes ( Fig. 1b and 1c) 23,28 and has a cross-linking effect on protein nanofibers.…”

Malignant H1299 tumour cells preferentially internalize iron-bound inositol hexakisphosphate

“…In plant cells, InsP 6 (inositol hexakisphosphate) mainly acts as a phosphate source and as a store of multivalent cations, because it binds Mg 2+ , Ca 2+ , Zn 2+ and Fe 3+ with high affinity [1]. Plant seeds express phytases during germination to get access to phosphate and multivalent cations, and mature plants use secreted phytases of rhizosphere bacteria and fungi to dephosphorylate soil InsP 6 [2,3].…”