Synthesis and metabolism of the myo-inositol pentakisphosphates

All six isomeric myo-inositol pentakisphosphates (InsP₅), consisting of the two meso compounds myo-inositol 1,3,4,5,6-pentakisphosphate [Ins(1,3,4,5,6)P₅] (18) and myo-inositol 1,2,3,4,6-pentakisphosphate [Ins(1,2,3,4,6)P₅] (22) and two pairs of enantiomers myo-inositol 1,2,4,5,6-pentakisphosphate [Ins(1,2,4,5,6)P₅] (15) myo-inositol 2,3,4,5,6-pentakisphosphate [Ins(2,3,4,5,6)P₅] (ent-15) and myo-inositol 1,2,3,5,6-pentakisphosphate [Ins(1,2,3,5,6)P₅] (20) myo-inositol 1,2,3,4,5-pentakisphosphate [Ins(1,2,3,4,5)P₅] (ent-20), respectively, were synthesized. These compounds have been found in tissue, and although not resolved as pure enantiomers, their primary metabolism in a cytosolic extract from fetal calf thymus was therefore investigated by analytical HPLC. Four isomers were dephosphorylated to singly defined inositol tetrakisphosphates, while Ins(1,2,4,5,6)P₅ was phosphorylated to myo-inositol hexakisphosphate (InsP₆). Interestingly, Ins(2,3,4,5,6)P₅ was the only isomer which was not metabolized. These data demonstrate that chemically synthesized, enantiomerically pure inositol pentakisphosphate isomers are valuable tools for the unravelling of the metabolic pathways of InsP₅ turnover in living cells.