Inositol phosphates: proliferation, metabolism and function

Abstract

After the initial discovery of receptor-linked generation of inositol(1,4,5)trisphosphate (Ins(1,4,5)P3) it was generally assumed that Ins(1,4,5)P3 and its proposed breakdown products inositol(1,4)bisphosphate (Ins(1,4)P2) and Ins1P, along with cyclic inositol monophosphate, were the only inositol phosphates found in significant amounts in animal cells. Since then, three levels of complexity have been introduced. Firstly, Ins(1,4,5)P3 can be phosphorylated to Ins(1,3,4,5)P4, and the subsequent metabolism of these two compounds has been found to be intricate and probably different between various tissues. The functions of Ins(1,4,5)P3 and Ins(1,3,4,5)P4 are almost certainly to regulate cytosolic Ca2+ concentrations, but the reasons for the labyrinth of the metabolic pathways after their deactivation by a specific 5-phosphatase remain obscure. Secondly, inositol pentakis- and hexakisphosphates have been found in many animal cells other than avian erythrocytes. It has been shown that their synthesis pathway is entirely separate from the inositol phosphates discussed above, both in terms of many of the isomers involved and probably in the subcellular localization; some possible functions of InsP5 and InsP6 are discussed here. Thirdly, cyclic inositol polyphosphates have been reported in stimulated tissues; the evidence for their occurrence in vivo and their possible physiological significance are also discussed.