Stepwise phosphorylation of myo-inositol leading to myo-inositol hexakisphosphate in Dictyostelium.
Although myo-inositol hexakisphosphate (InsP6; phytate) is the most abundant inositol phosphate in nature and probably has a wide variety of functions, 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(1,4,5)P3) are known. 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(1,4,5)P3. The intermediates between myo-inositol and InsP6 are Ins3P, Ins(3,6)P2, Ins(3,4,6)P3, Ins(1,3,4,6)P4 and Ins(1,3,4,5,6)P5. The 3- and 5-phosphates of InsP6 take part in futile cycles in which Ins(1,2,4,5,6)P5 and Ins(1,2,3,4,6)P5 are rapidly formed by dephosphorylation of InsP6, only to be rephosphorylated to yield their precursor.
Stephens
L R
LR
Biochemistry Department, AFRC Institute of Animal Physiology & Genetics Research, Cambridge Research Station, UK.
Irvine
R F
RF
D004023:Dictyostelium / Q000378:metabolism*; D007294:Inositol / Q000378:metabolism*; D007295:Inositol Phosphates / Q000302:isolation & purification / Q000378:metabolism; D008954:Models, Biological; D010761:Phosphorus Radioisotopes; D010766:Phosphorylation; D010833:Phytic Acid / Q000096:biosynthesis*; D011865:Radioisotope Dilution Technique; D014316:Tritium
D007295:Inositol Phosphates; D010761:Phosphorus Radioisotopes; D014316:Tritium; D007294:Inositol; D010833:Phytic Acid