IP₃ and DAG are generated by the cleavage of which phospholipid by phospholipase C?

Explanation

## Phospholipase C and the IP₃/DAG Pathway **Key Point:** Phospholipase C (PLC) cleaves phosphatidylinositol 4,5-bisphosphate (PIP₂) to generate the two critical second messengers: inositol 1,4,5-trisphosphate (IP₃) and diacylglycerol (DAG). ### The PLC-Mediated Cleavage Reaction ```mermaid flowchart TD A[Hormone binds Gq-coupled GPCR]:::outcome --> B[Gq protein activated]:::action B --> C[Phospholipase C activated]:::action C --> D[PIP₂ cleaved]:::action D --> E[IP₃ released into cytosol]:::outcome D --> F[DAG remains in membrane]:::outcome E --> G[IP₃ binds IP₃ receptor on ER]:::action G --> H[Ca²⁺ release from ER]:::outcome F --> I[DAG activates PKC]:::action ``` ### Structural Details of the Reaction PIP₂ is a phosphorylated form of phosphatidylinositol located in the inner leaflet of the plasma membrane. PLC catalyzes hydrolysis of the phosphodiester bond between the inositol head group and the glycerol backbone: - **Product 1**: Inositol 1,4,5-trisphosphate (IP₃) — a water-soluble molecule that diffuses through the cytosol - **Product 2**: Diacylglycerol (DAG) — a lipophilic molecule that remains anchored in the membrane **High-Yield:** The simultaneous generation of two distinct second messengers (IP₃ and DAG) from a single phospholipid allows coordinated signaling: IP₃ mobilizes intracellular Ca²⁺, while DAG activates protein kinase C (PKC). ### Comparison of Second Messenger Pathways | Feature | cAMP Pathway | IP₃/DAG Pathway | |---------|--------------|------------------| | **Trigger** | Gs-coupled GPCR | Gq-coupled GPCR | | **Enzyme** | Adenylyl cyclase | Phospholipase C | | **Substrate** | ATP | PIP₂ | | **Second messengers** | cAMP only | IP₃ + DAG | | **Primary effect** | PKA activation | Ca²⁺ release + PKC activation | | **Duration** | Transient (cAMP degraded by phosphodiesterase) | Transient (IP₃ dephosphorylated, DAG phosphorylated) | **Clinical Pearl:** Mutations in genes encoding PLC or its regulators can impair IP₃/DAG signaling, affecting processes as diverse as immune cell activation, muscle contraction, and neuronal plasticity. **Mnemonic:** **PIP₂ → IP₃ + DAG** — "**P**hosphate **I**nositol **P**roduces **I**nositol-**P**hosphate and **D**iacyl**G**lycerol"