Pancreatic triacylglycerol lipase–colipase complex (PTL-CLPS)

The pancreatic lipase–colipase complex is the primary enzymatic unit responsible for the hydrolysis of dietary triglycerides in the human digestive system. It consists of pancreatic triacylglycerol lipase (PNLIP), a member of the serine hydrolase family, and its essential protein cofactor, colipase (CLPS). In the duodenum, bile salts normally inhibit lipase by displacing it from the lipid-water interface; however, colipase overcomes this inhibition by anchoring the lipase to the lipid droplets and stabilizing its active, open-lid conformation. This complex specifically cleaves the sn-1 and sn-3 ester bonds of triglycerides to produce free fatty acids and 2-monoacylglycerols, which are then packaged into micelles for absorption. Because it is the rate-limiting step in lipid assimilation, the complex is a significant therapeutic target for managing obesity and hyperlipidemia. Pharmacological inhibitors like orlistat bind covalently to the active site serine of the lipase, preventing fat digestion and thereby reducing caloric absorption. While effective for weight loss, these drugs often cause gastrointestinal side effects such as steatorrhea due to the presence of undigested fats in the colon.

Other names

Pancreatic lipase–co-lipase complexPancreatic triacylglycerol lipaseColipasePTLPNLIPCLPSSteapsinPancreatic lipase

Covalent inhibition of the active site serine (Ser152) within the lipase, preventing the hydrolysis of dietary fats into absorbable components.