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.
Biochemistry Department, AFRC Institute of Animal Physiology & Genetics Research, Cambridge Research Station, UK.
L R
LR
Stephens
R F
RF
Irvine
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