The behaviour of inositol 1,3,4,5,6-pentakisphosphate in the presence of the major biological metal cations

The inositol phosphates are ubiquitous metabolites in eukaryotes, of which the most abundant are inositol hexakisphosphate (InsP(6)) and inositol 1,3,4,5,6-pentakisphosphate [Ins(1,3,4,5,6)P(5))]. These two compounds, poorly understood functionally, have complicated complexation and solid formation behaviours with multivalent cations. For InsP(6), we have previously described this chemistry and its biological implications (Veiga et al. in J Inorg Biochem 100:1800, 2006; Torres et al. in J Inorg Biochem 99:828, 2005). We now cover similar ground for Ins(1,3,4,5,6)P(5), describing its interactions in solution with Na(+), K(+), Mg(2+), Ca(2+), Cu(2+), Fe(2+) and Fe(3+), and its solid-formation equilibria with Ca(2+) and Mg(2+). Ins(1,3,4,5,6)P(5) forms soluble complexes of 1:1 stoichiometry with all multivalent cations studied. The affinity for Fe(3+) is similar to that of InsP(6) and inositol 1,2,3-trisphosphate, indicating that the 1,2,3-trisphosphate motif, which Ins(1,3,4,5,6)P(5) lacks, is not absolutely necessary for high-affinity Fe(3+) complexation by inositol phosphates, even if it is necessary for their prevention of the Fenton reaction. With excess Ca(2+) and Mg(2+), Ins(1,3,4,5,6)P(5) also forms the polymetallic complexes [M(4)(H(2)L)] [where L is fully deprotonated Ins(1,3,4,5,6)P(5)]. However, unlike InsP(6), Ins(1,3,4,5,6)P(5) is predicted not to be fully associated with Mg(2+) under simulated cytosolic/nuclear conditions. The neutral Mg(2+) and Ca(2+) complexes have significant windows of solubility, but they precipitate as [Mg(4)(H(2)L)]·23H(2)O or [Ca(4)(H(2)L)]·16H(2)O whenever they exceed 135 and 56 μM in concentration, respectively. Nonetheless, the low stability of the [M(4)(H(2)L)] complexes means that the 1:1 species contribute to the overall solubility of Ins(1,3,4,5,6)P(5) even under significant Mg(2+) or Ca(2+) excesses. We summarize the solubility behaviour of Ins(1,3,4,5,6)P(5) in straightforward plots. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s00775-009-0510-z) contains supplementary material, which is available to authorized users.