Pancreatic triacylglycerol lipase (PTL)

Pancreatic triacylglycerol lipase is an enzyme secreted by the pancreas that plays a central role in dietary fat digestion. It catalyzes the hydrolysis of triglycerides at positions 1 and 3 on glycerol backbones within emulsified lipid droplets in the small intestine—producing mainly monoglycerides and free fatty acids that can be absorbed by enterocytes. This process requires colipase for optimal activity at lipid-water interfaces. The enzyme’s structure features a catalytic triad typical of serine hydrolases with an active site covered by a lid domain that undergoes conformational change upon substrate binding/interfacial activation. Clinically, it serves both as a drug target for anti-obesity agents like orlistat—which block its function—and as a biomarker for acute pancreatitis when found elevated in serum.

Other names

Pancreatic lipaseTriacylglycerol acyl hydrolaseTriglyceride lipaseSteapsinPLPTLEC 3.1.1.3

Inhibition of enzymatic activity to reduce hydrolysis/absorption of dietary fats; e.g., orlistat covalently binds to the active site serine residue, blocking substrate access and thus fat digestion/absorption