STEPWISE PHOSPHORYLATION OF MYOINOSITOL LEADING TO MYOINOSITOL HEXAKISPHOSPHATE IN DICTYOSTELIUM

ALTHOUGH myo-inositol hexakisphosphate (InsP6; phytate) is the most abundant inositol phosphate in nature1 and probably has a wide variety of functions2-8, 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. © 1990 Nature Publishing Group.