What is lipase?

What is Lipase?

Lipase is a digestive enzyme secreted primarily by the pancreas that catalyzes the hydrolysis of triglycerides (fats) into fatty acids and glycerol, playing a critical role in fat digestion and serving as the most sensitive and specific laboratory marker for diagnosing acute pancreatitis. 1, 2

Biochemical Structure and Properties

• Lipase is a glycoprotein consisting of 420-449 amino acid residues with a molecular weight of 46,000-56,000 for pancreatic lipase and 32,000-39,000 for serum lipase 3
• The enzyme contains a catalytic triad (Asp-His-Ser) where serine serves as the nucleophilic residue essential for catalysis 3
• Lipase has an optimal pH between 7.5 and 10.0, depending on reaction conditions 3
• The enzyme exhibits a unique α/β-hydrolase fold structure with a core domain and a cap domain that includes a "lid" covering the active site in its closed conformation 4

Sources and Distribution

• Pancreatic lipase is the primary source, secreted by pancreatic acinar cells and representing the major lipolytic enzyme for dietary fat digestion 1, 4
• The concentration gradient between pancreatic tissue and serum is approximately 20,000-fold 3
• Lipase is also present in gastric tissue (gastric lipase), intestines, liver (hepatic lipase), and various other tissues including adipose tissue and skeletal muscle 1, 5
• Human gastric lipase is secreted by chief cells in the fundic part of the stomach and plays an important preparatory role before pancreatic lipase action 4

Physiological Function

• The primary function is digestion of dietary fats, with pancreatic lipase responsible for hydrolyzing over 80% of total dietary triglycerides 6, 1
• Lipase requires cofactors for optimal activity: colipase (a water-soluble, heat-stable protein), bile salts, and calcium ions 3
• The enzyme acts at the lipid-water interface, where it can hydrolyze fats into fatty acids and glycerol, and can reverse this reaction in non-aqueous media 7
• Gastric lipase initiates fat digestion in the acidic stomach environment and continues to act in the duodenum in synergy with pancreatic lipase 4
• Humans lack alternative mechanisms for fat digestion, making lipase uniquely critical compared to protein and carbohydrate digestive enzymes 1

Clinical Significance in Diagnosis

• Serum lipase is the preferred first-line laboratory test for diagnosing acute pancreatitis, demonstrating superior sensitivity (79-91%) compared to amylase (62-72%) 1, 2, 8
• The diagnostic threshold is ≥3 times the upper limit of normal, which provides optimal specificity for acute pancreatitis 2, 8
• Lipase remains elevated for 8-14 days after onset, compared to amylase's 3-7 days, providing a larger diagnostic window for patients presenting later in their disease course 1, 2
• Serum lipase rises within 4-8 hours of acute pancreatitis onset, peaks at 24 hours, and normalizes over 8-14 days 1

Important Clinical Caveats

• Pancreatic lipase is less stable than other pancreatic enzymes against acid denaturation in the duodenum and is rapidly destroyed by pancreatic proteases, particularly chymotrypsin, making lipid digestion vulnerable in pathologic conditions 1
• In chronic pancreatitis, lipase production may be significantly reduced due to pancreatic tissue destruction, potentially resulting in normal or only mildly elevated levels during acute exacerbations 9
• Lipase elevation can occur in non-pancreatic diseases including renal disease, appendicitis, acute cholecystitis, and bowel obstruction, though pancreatic pathology remains the primary cause 1
• The degree of enzyme elevation does not correlate with disease severity—patients can have severe pancreatitis with modest enzyme elevations 8

Therapeutic Applications

• Pancreatic enzyme replacement therapy (PERT) uses exogenous lipase to treat exocrine pancreatic insufficiency, with all FDA-approved formulations being of porcine origin and labeled based on USP lipase content 1
• PERT dosing focuses on lipase content, with initial treatment requiring at least 40,000 USP units of lipase during each meal in adults and half that amount with snacks 1
• Lipase activity in PERT ranges from 10-120 U/mL in the stomach and 80-7000 U/mL in the duodenal tract under physiologic conditions 1
• Pancrelipase (a combination of lipase, protease, and amylase) can be used to aid digestion of cornstarch in glycogen storage disease type III 1