Gastric and pancreatic triacylglycerol lipases (GL/PL)

Gastric and pancreatic triacylglycerol lipases are essential digestive enzymes that catalyze the hydrolysis of dietary fats into free fatty acids and monoglycerides (UniProt P04054, 2024). Gastric lipase is secreted by the gastric chief cells and initiates the breakdown of triglycerides in the acidic environment of the stomach, which is particularly critical for lipid processing in neonates (UniProt P07098, 2024). Pancreatic lipase is the primary enzyme for fat digestion in adults, secreted by the exocrine pancreas into the duodenum where it performs the majority of fat hydrolysis in conjunction with its cofactor, colipase (UniProt P04054, 2024). These enzymes are significant therapeutic targets for the management of obesity; pharmacological inhibition by drugs such as Orlistat prevents the absorption of approximately 30% of dietary fat by covalently binding to the active site serine of the enzymes (StatPearls, 2023). In addition to being targets for inhibition, these enzymes are administered as pancreatic enzyme replacement therapy (PERT) for conditions such as cystic fibrosis or chronic pancreatitis to manage malabsorption (NIH, 2023). Therapeutic use or inhibition of these lipases requires careful monitoring of nutritional status and gastrointestinal side effects.

Other names

Gastric lipasePancreatic triacylglycerol lipasePancreatic lipaseLIPFPNLIPSteapsinTributyraseGastric triacylglycerol lipase

Orlistat and similar agents act via covalent inhibition of the active site serine residue of both gastric and pancreatic lipases within the gastrointestinal lumen. This prevents the enzymes from hydrolyzing dietary triglycerides into absorbable free fatty acids and monoglycerides, thereby reducing caloric intake from fats (StatPearls, 2023; PubChem CID 3034034, 2024).