Membrane phosphatidylinositol cycle and downstream signaling. PI(4,5)P2 is cleaved by PLC (phospholipase C, Gq-coupled or RTK-coupled) into IP3 (releases ER Ca2+ via IP3R) and DAG (activates PKC). IP3 is degraded by sequential phosphatases — inositol monophosphatase (IMPA1) is the proposed LITHIUM TARGET for bipolar disorder ("inositol depletion hypothesis"). Lithium also inhibits GSK-3β; the relative contribution of each to mood-stabilization is debated. Inositol supplementation has been investigated for PCOS, depression, and lithium-augmentation strategies (with mixed evidence). PI(3,4,5)P3 (made from PI(4,5)P2 by PI3K) is a separate signaling axis driving AKT — see mtor_signaling pathway.
Organ Systems
nervous
endocrine
Pathway Steps
phosphatidylinositol-4-5-bisphosphate → inositol-trisphosphate — via PLC β (Gq) or PLC γ (RTK) — cleaves PIP2 into IP3 + DAG. Gq-coupled receptors activate phospholipase C, which cleaves the membrane lipid PIP2 into two second messengers: inositol-1,4,5-trisphosphate (IP3) and diacylglycerol (DAG). IP3 is the soluble arm that mobilizes calcium, while DAG stays in the membrane to activate PKC — splitting one signal into two.
inositol-trisphosphate → inositol — via sequential phosphatases; IMPA1 dephosphorylates IP1 — LITHIUM TARGET. IP3 diffuses to the ER and opens IP3 receptors, releasing stored Ca²⁺ into the cytosol — the calcium signal behind secretion, contraction, and gene expression. IP3 is then dephosphorylated stepwise back to free inositol, terminating the signal.
inositol → phosphatidylinositol — via PI synthase + CDP-DAG reincorporation; closes cycle. Free inositol is recycled to rebuild phosphatidylinositol and replenish the PIP2 pool. Lithium inhibits inositol monophosphatase in this recycling pathway — the leading “inositol-depletion” hypothesis for its mood-stabilizing action in bipolar disorder.