Heterogeneity Amongst Myo-Inositol Derivatives: Metabolism of Second Messengers and Synthesis of Co-Signals

Abstract

Myo-inositol is one of nine possible isomers of hexahydroxy cyclohexane in which the 2-hydroxyl is axial to the plane of the 6 membered ring with the remaining hydroxyl groups all being equatorial (Cosgrove, 1980). This configuration ensures that simple derivatives of myo-inositol, such as inositol phosphates, can occur in a variety of isomeric forms e.g. there are 20 possible inositol trisphosphate isomers. Recent studies have uncovered a bewildering complexity of cellular inositol metabolism, much of which is concerned with metabolism of the Ca²⁺-mobilising second messenger, inositol 1,4,5-trisphosphate (Ins1,4,5P₃ ³). On the other hand, certain inositol phosphates isomers appear to be involved with the synthesis of inositol polyphosphates such as inositol pentakis- and hexakisphosphate (InsP₅ and InsP₆) whose function and metabolic relationships to the fast signalling events triggered by receptor stimulated cleavage of phosphatidylinositol 4,5-bisphosphate (PtdIns4,5P₂) are not yet understood (see Downes, 1988 and references therein). In addition a novel inositol phospholipid (phosphatidylinositol 3-phosphate, PtdIns3P) has recently been described (Whitman et al, 1988; Stephens et al 1989b) whose synthesis may be regulated by the association of a Ptdlns 3-kinase with activated tyrosine kinases such as the receptor for platelet derived growth factor (PDGF; Whitman et al, 1987).