Stepwise phosphorylation of myo-inositol leading to myo-inositol hexakisphosphate in Dictyostelium

Abstract

ALTHOUGH myo-inositol hexakisphosphate (InsP₆; phytate) is the most abundant inositol phosphate in nature¹ and probably has a wide variety of functions^2–8, neither the route of its synthesis from myo-inositol nor its metabolic relationships with other inositol-containing compounds (such as the second messenger inositol 1,4,5-trisphosphate, Ins(l,4,5)P₃) are known⁹. Here we report that the pathway by which InsP₆ is synthesized in the cellular slime mould Dictyostelium, and in cell-free preparations derived from them, is catalysed by a series of soluble ATP-dependent kinases independently of the metabolism of both phosphatidylinositol and Ins(l,4,5)P₃ (refs 10,11). The intermediates between myo-inositol and InsP₆ are Ins3P, Ins(3,6)P₂, Ins(3,4,6)P₃, Ins(l,3,4,6)P₄ and Ins(l,3,4,5,6)P₅. The 3- and 5-phosphates of InsP₆ take part in futile cycles in which Ins(l,2,4,5,6)P₅ and Ins(l,2,3,4,6)P₅ are rapidly formed by dephosphorylation of InsP₆, only to be rephosphorylated to yield their precursor.