The biological relevance of the binding of calcium ions by inositol phosphates.
The binding of Ca2+ (chelation) by myo-inositol polyphosphates at pH 7.0 was studied using a Ca(2+)-sensitive electrode. Glucose 6-phosphate (used as a model for a monophosphate) bound Ca2+ with an affinity of 152 +/- 31 liters/mol and a molar ratio of 0.94 +/- 0.02. Inositol 3,4-bisphosphate, inositol 1,4,5-trisphosphate, inositol 1,3,4,5-tetrakisphosphate, and inositol hexakisphosphate showed affinities of 9.0 +/- 2.1 x 10(3), 6.3 +/- 1.5 x 10(3), 6.2 x 10(4), and 1.92 +/- 0.47 x 10(5) liters/mol, respectively, and molar ratios of 0.92 +/- 0.49, 0.95 +/- 0.10, 0.75, and 2.5 +/- 0.5. In general, the affinity increased with the number of phosphate substituents on the inositol ring, although the stereochemistry is also expected to be important. This suggests that for the physiologically relevant inositol phosphates (tris-, tetrakis-, pentakis-, and hexakis-) half-maximal Ca2+ binding will occur in the Ca2+ concentration range of approximately 5 x 10(-6) to 2 x 10(-4) M. This range lies between the basal intracellular and the fee extracellular Ca2+ levels (10(-7) and 10(-3) M), respectively, and may therefore be of physiological importance. Chelation provides a possible simple explanation for the inhibition by Ca2+ of inositol 1,4,5-trisphosphate binding to its receptor in rat cerebellum and other tissues. It may also have a role in limiting inositol phosphate-mediated increases in intracellular Ca2+.
Luttrell
B M
BM
Department of Endocrinology, Royal North Shore Hospital, St. Leonards, New South Wales, Australia.
D001665:Binding Sites; D002118:Calcium / Q000378:metabolism*; D004566:Electrodes; D019298:Glucose-6-Phosphate; D005958:Glucosephosphates / Q000378:metabolism; D006863:Hydrogen-Ion Concentration; D015544:Inositol 1,4,5-Trisphosphate / Q000378:metabolism; D007295:Inositol Phosphates / Q000737:chemistry / Q000378:metabolism*; D008968:Molecular Conformation; D013329:Structure-Activity Relationship
D005958:Glucosephosphates; D007295:Inositol Phosphates; C081655:inositol-1,3,4,5-tetrakisphosphate; C051854:inositol 3,4-bisphosphate; D019298:Glucose-6-Phosphate; D015544:Inositol 1,4,5-Trisphosphate; D002118:Calcium