## Pancreatic Lipase: The Primary Fat-Digesting Enzyme ### Role of Pancreatic Lipase **Key Point:** **Pancreatic lipase** is the main enzyme responsible for dietary triglyceride digestion. It hydrolyzes triglycerides at the **1 and 3 positions** (terminal positions), producing **2-monoglycerides and free fatty acids**. ### Mechanism of Action 1. **Substrate:** Dietary triglycerides (triacylglycerols) 2. **Products:** 2-monoglycerides + 2 free fatty acids per triglyceride molecule 3. **Location:** Duodenum and proximal jejunum 4. **pH optimum:** Slightly alkaline (pH 7–8), maintained by bicarbonate from pancreatic secretion 5. **Cofactor:** **Colipase** (not an enzyme itself) — essential cofactor that anchors lipase to the lipid droplet surface and prevents bile salt inhibition ### Comparison of Pancreatic Fat-Digesting Enzymes | Enzyme | Substrate | Products | Role | |--------|-----------|----------|------| | **Pancreatic lipase** | Triglycerides | 2-Monoglycerides + 2 FFAs | Primary fat digestion (90%) | | **Phospholipase A₂** | Phospholipids | Lysophospholipids + FFAs | Phospholipid digestion | | **Cholesterol esterase** | Cholesterol esters | Free cholesterol + FFAs | Cholesterol ester hydrolysis | **High-Yield:** Pancreatic lipase accounts for **~90% of fat digestion**. Gastric lipase (secreted by chief cells) contributes only ~10% and works in the acidic stomach environment. **Mnemonic:** **COLA** — **Co**lipase is the **L**ipase **A**ctivator. Colipase is essential for lipase function in the presence of bile salts. **Clinical Pearl:** In **pancreatic insufficiency** (chronic pancreatitis, cystic fibrosis), reduced pancreatic lipase leads to **steatorrhea** (fatty stools). Pancreatic enzyme replacement therapy includes lipase supplementation. **Warning:** Colipase is NOT an enzyme — it is a **cofactor/coenzyme** that facilitates lipase binding to lipid droplets. Students often confuse it with an active enzyme. [cite:Guyton & Hall 13e Ch 64]
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