Neuropharmacology & Neurotherapeutics
Eteplirsen
Sep. 16, 2021
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Outline of pathways for synthesis of inositol phosphates and phosphoinositides
Inositol can be obtained from dietary sources or synthesized from D-glucose by the sequential action of hexokinase (HK), myo-inositol-1-phosphate synthase (MIPS), and inositol monophosphatase (IMPas). The structures of myo-inositol and phosphatidylinositol (inositol lipids are shaded gray) form the backbone for synthesis of inositol phosphate (IP) and phosphoinositide (PI) molecules through the action of multiple kinases and/or phosphatases. Phosphorylation/dephosphorylation steps can be mediated by several enzymes (kinases in blue text, phosphatases in purple text). Some kinases exist in multiple isoforms (eg, PIP5K and PI3K [PI3-kinase]), whereas several phosphatases can act to dephosphorylate PI(3,4,5)P3 (eg, INPP5E, SHIP1, and SHIP2). Some enzymes act at multiple steps (eg, IPMK acts to phosphorylate inositol at several steps). Downstream functional effects of key molecules are indicated in italics (green text). Abbreviations: PLC: phospholipase C; DAG: diacylglycerol; PKC: protein kinase C; IPMK: inositol phosphate multikinase; ITPK1: inositol 1,3,4-triphosphate 5/6 kinase. (Source: Greene ND, Leung KY, Copp AJ. Inositol, neural tube closure and the prevention of neural tube defects. Birth Defects Res 2017;109[2]:68-80. Creative Commons Attribution [CC BY 4.0] license, creativecommons.org/licenses/by/4.0.)