Q.15 Phospholipase C cleaves phosphatidyl-inositol 4, 5, bisphosphate into the following:
(1) Phosphatidyl-choline and Phosphatidic acid
(2) Phosphatidic acid and Choline
(3) Inositol 1, 4, 5-triphosphate and diacylglycerol
(4) Triacylglycerol and Inositol-triphosphate
Phospholipase C (PLC) plays a central role in cell signaling by hydrolyzing a key membrane lipid. The question “Phospholipase C cleaves phosphatidyl-inositol 4,5-bisphosphate into the following:” tests this classic biochemistry reaction with options (1) Phosphatidyl-choline and Phosphatidic acid, (2) Phosphatidic acid and Choline, (3) Inositol 1,4,5-triphosphate and diacylglycerol, (4) Triacylglycerol and Inositol-triphosphate.
Correct Answer: (3) Inositol 1,4,5-triphosphate and diacylglycerol
PLC-β (activated by Gq-coupled receptors) specifically cleaves the phosphodiester bond in PIP2 (phosphatidylinositol 4,5-bisphosphate), yielding IP3 and DAG as second messengers.
PLC-PIP2 Reaction Mechanism
PIP2 resides in the inner plasma membrane leaflet. Upon GPCR activation → Gq → PLC-β, the enzyme attacks the glycerol-phosphoinositol bond:
PIP2 → IP3 (soluble, Ca²⁺ release) + DAG (lipid, PKC activation)
IP3 diffuses to ER/IP3R channels, releasing Ca²⁺. DAG recruits PKC to membrane with elevated Ca²⁺, amplifying signals like contraction, secretion, and gene expression.
Why IP3 + DAG? Signaling Power
This dual second messenger system creates synergy: Ca²⁺ spikes from IP3 synergize with DAG-activated PKC for robust downstream effects. It’s evolutionarily conserved across eukaryotes.
Option Analysis: Incorrect Products
(1) Phosphatidyl-choline and Phosphatidic acid
Phosphatidylcholine (PC) hydrolysis by Phospholipase C (PLC on PC) yields diacylglycerol + phosphocholine—not PIP2’s natural substrate. Phosphatidic acid comes from Phospholipase D (PLD) or Phospholipase A2 pathways.
(2) Phosphatidic acid and Choline
Phospholipase D (PLD) cleaves PC headgroup, producing phosphatidic acid + choline. PLC never generates free choline from PIP2.
(4) Triacylglycerol and Inositol-triphosphate
Triacylglycerols (TAGs) are neutral lipid droplets, not membrane phospholipids. No phospholipase produces TAGs; lipases handle that. IP3 nomenclature is also imprecise here.
Phospholipase Pathways: Comparison Table
| Enzyme | Substrate | Products | Signaling Role |
|---|---|---|---|
| PLC | PIP2 | IP3 + DAG | Ca²⁺ release, PKC activation |
| PLD | PC | Phosphatidic acid + Choline | Membrane curvature, mTOR |
| PLA2 | PC/PE | Lysophospholipid + Fatty acid | Arachidonic acid, eicosanoids |
| PC-PLC | PC | DAG + Phosphocholine | Alternative PKC pathway |
Biochemical Relevance for Exams
Mastering Phospholipase C cleaves reactions clarifies GPCR → second messenger cascades, drug targets (e.g., antipsychotics blocking PLC), and lipid signaling in physiology/pathology.
