Pancreatic lipase

Not to be confused with Bile salt-dependent lipase (CEL).

PNLIP
Identifiers
Aliases	PNLIP, PNLIPD, PTL, PL, pancreatic lipase
External IDs	OMIM: 246600; MGI: 97722; GeneCards: PNLIP
Available structures PDB Ortholog search: PDBe RCSB List of PDB id codes 1LPA, 1LPB, 1N8S
Enzyme activity EC # BRENDA ExPASy KEGG MetaCyc 3.1.1.3 ↗ ↗ ↗ ↗
Gene location (Human) Chr. Chromosome 10 (human) Band 10q25.3 Start 116,545,931 bp End 116,567,855 bp
Gene location (Mouse) Chr. Chromosome 19 (mouse) Band 19 D2|19 54.46 cM Start 58,640,930 bp End 58,670,220 bp
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in body of pancreas islet of Langerhans testicle beta cell right coronary artery ectocervix right lobe of liver Descending thoracic aorta canal of the cervix right uterine tube Top expressed in pyloric antrum islet of Langerhans lumbar spinal ganglion duodenum gastrula esophagus spleen right ventricle sternocleidomastoid muscle superior frontal gyrus More reference expression data BioGPS n/a
Gene ontology Molecular function triglyceride lipase activity carboxylic ester hydrolase activity hydrolase activity metal ion binding lipase activity protein binding Cellular component extracellular region extracellular space Biological process lipid catabolic process positive regulation of triglyceride lipase activity intestinal cholesterol absorption lipid metabolism retinoid metabolic process lipid digestion Sources:Amigo / QuickGO
Orthologs Databases NCBI: entry; OMA: entry Species Human Mouse Entrez 5406 69060 Ensembl ENSG00000175535 ENSMUSG00000046008 UniProt P16233 Q6P8U6 RefSeq (mRNA) NM_000936 NM_026925 RefSeq (protein) NP_000927 NP_081201 Location (UCSC) Chr 10: 116.55 – 116.57 Mb Chr 19: 58.64 – 58.67 Mb PubMed search
Wikidata
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Pancreatic lipase, also known as pancreatic triacylglycerol lipase, is an enzyme that in humans is encoded by the PNIP gene. It is secreted from the pancreas, and is one of the primary lipase enzymes that hydrolyzes (breaks down) dietary fat molecules in the human digestive system.

Function

Hydrolysis of a triglyceride 1

Pancreatic lipase is one of the main digestive enzymes, ultimately converting triglyceride substrates found in ingested oils to monoglycerides and free fatty acids.

Triacylglycerol + 2 H₂O $\rightleftharpoons$ 2-monoacylglycerol + 2 fatty acid anions

Bile salts secreted from the liver and stored in gallbladder are released into the duodenum, where they coat and emulsify large fat droplets into smaller droplets, thus increasing the overall surface area of the fat, which allows the lipase to break apart the fat more effectively. The resulting monomers (2 free fatty acids and one 2-monoacylglycerol) are then moved by way of peristalsis along the small intestine to be absorbed into the lymphatic system by a specialized vessel called a lacteal. This protein belongs to the pancreatic lipase family.

Unlike some pancreatic enzymes that are activated by proteolytic cleavage (e.g., trypsinogen), pancreatic lipase is secreted in its final form. However, it becomes efficient only in the presence of colipase in the duodenum.

Medical significance

Diagnostic value

Pancreatic lipase is secreted from acinar cells into the duodenum through the duct system of the pancreas. Its concentration in serum is normally very low. Under extreme disruption of pancreatic function, such as pancreatitis or pancreatic adenocarcinoma, the pancreas may begin to autolyse and release pancreatic enzymes including pancreatic lipase into serum. Thus, through measurement of serum concentration of pancreatic lipase, acute pancreatitis can be diagnosed.

Inhibitors

Lipase inhibitors such as orlistat have been used as a treatment for obesity.

Further reading

• Crandall WV, Lowe ME (2001). "Colipase residues Glu64 and Arg65 are essential for normal lipase-mediated fat digestion in the presence of bile salt micelles". J. Biol. Chem. 276 (16): 12505–12. doi:10.1074/jbc.M009986200. PMID 11278590.
• Freie AB, Ferrato F, Carrière F, Lowe ME (2006). "Val-407 and Ile-408 in the beta5'-loop of pancreatic lipase mediate lipase-colipase interactions in the presence of bile salt micelles". J. Biol. Chem. 281 (12): 7793–800. doi:10.1074/jbc.M512984200. PMC 3695395. PMID 16431912.
• Hegele RA, Ramdath DD, Ban MR, Carruthers MN, Carrington CV, Cao H (2001). "Polymorphisms in PNLIP, encoding pancreatic lipase, and associations with metabolic traits". J. Hum. Genet. 46 (6): 320–4. doi:10.1007/s100380170066. PMID 11393534.
• Chahinian H, Sias B, Carrière F (2000). "The C-terminal domain of pancreatic lipase: functional and structural analogies with c2 domains". Curr. Protein Pept. Sci. 1 (1): 91–103. PMID 12369922.
• Ranaldi S, Belle V, Woudstra M, Rodriguez J, Guigliarelli B, Sturgis J, Carriere F, Fournel A (2009). "Lid opening and unfolding in human pancreatic lipase at low pH revealed by site-directed spin labeling EPR and FTIR spectroscopy". Biochemistry. 48 (3): 630–8. doi:10.1021/bi801250s. PMID 19113953.
• Grupe A, Li Y, Rowland C, Nowotny P, Hinrichs AL, Smemo S, Kauwe JS, Maxwell TJ, Cherny S, Doil L, Tacey K, van Luchene R, Myers A, Wavrant-De Vrièze F, Kaleem M, Hollingworth P, Jehu L, Foy C, Archer N, Hamilton G, Holmans P, Morris CM, Catanese J, Sninsky J, White TJ, Powell J, Hardy J, O'Donovan M, Lovestone S, Jones L, Morris JC, Thal L, Owen M, Williams J, Goate A (2006). "A scan of chromosome 10 identifies a novel locus showing strong association with late-onset Alzheimer disease". Am. J. Hum. Genet. 78 (1): 78–88. doi:10.1086/498851. PMC 1380225. PMID 16385451.
• Thomas A, Allouche M, Basyn F, Brasseur R, Kerfelec B (2005). "Role of the lid hydrophobicity pattern in pancreatic lipase activity". J. Biol. Chem. 280 (48): 40074–83. doi:10.1074/jbc.M502123200. PMID 16179352.
• van Tilbeurgh H, Egloff MP, Martinez C, Rugani N, Verger R, Cambillau C (1993). "Interfacial activation of the lipase-procolipase complex by mixed micelles revealed by X-ray crystallography". Nature. 362 (6423): 814–20. doi:10.1038/362814a0. PMID 8479519.
• Lessinger JM, Arzoglou P, Ramos P, Visvikis A, Parashou S, Calam D, Profilis C, Férard G (2003). "Preparation and characterization of reference materials for human pancreatic lipase: BCR 693 (from human pancreatic juice) and BCR 694 (recombinant)". Clin. Chem. Lab. Med. 41 (2): 169–76. doi:10.1515/CCLM.2003.028. PMID 12667003.
• Colin DY, Deprez-Beauclair P, Allouche M, Brasseur R, Kerfelec B (2008). "Exploring the active site cavity of human pancreatic lipase". Biochem. Biophys. Res. Commun. 370 (3): 394–8. doi:10.1016/j.bbrc.2008.03.043. PMID 18353248.
• Ramos P, Coste T, Piémont E, Lessinger JM, Bousquet JA, Chapus C, Kerfelec B, Férard G, Mély Y (2003). "Time-resolved fluorescence allows selective monitoring of Trp30 environmental changes in the seven-Trp-containing human pancreatic lipase". Biochemistry. 42 (43): 12488–96. doi:10.1021/bi034900e. PMID 14580194.
• Yang Y, Lowe ME (1998). "Human pancreatic triglyceride lipase expressed in yeast cells: purification and characterization". Protein Expr. Purif. 13 (1): 36–40. doi:10.1006/prep.1998.0874. PMID 9631512.
• Sims HF, Jennens ML, Lowe ME (1993). "The human pancreatic lipase-encoding gene: structure and conservation of an Alu sequence in the lipase gene family". Gene. 131 (2): 281–5. doi:10.1016/0378-1119(93)90307-O. PMID 8406023.
• Grandval P, De Caro A, De Caro J, Sias B, Carrière F, Verger R, Laugier R (2004). "Critical evaluation of a specific ELISA and two enzymatic assays of pancreatic lipases in human sera". Pancreatology. 4 (6): 495–503, discussion 503-4. doi:10.1159/000080246. PMID 15316225.
• Belle V, Fournel A, Woudstra M, Ranaldi S, Prieri F, Thomé V, Currault J, Verger R, Guigliarelli B, Carrière F (2007). "Probing the opening of the pancreatic lipase lid using site-directed spin labeling and EPR spectroscopy". Biochemistry. 46 (8): 2205–14. doi:10.1021/bi0616089. PMID 17269661.
• Lowe ME (1997). "Structure and function of pancreatic lipase and colipase". Annu. Rev. Nutr. 17: 141–58. doi:10.1146/annurev.nutr.17.1.141. PMID 9240923.
• Bourbon-Freie A, Dub RE, Xiao X, Lowe ME (2009). "Trp-107 and trp-253 account for the increased steady state fluorescence that accompanies the conformational change in human pancreatic triglyceride lipase induced by tetrahydrolipstatin and bile salt". J. Biol. Chem. 284 (21): 14157–64. doi:10.1074/jbc.M901154200. PMC 2682864. PMID 19346257.
• Ranaldi S, Belle V, Woudstra M, Bourgeas R, Guigliarelli B, Roche P, Vezin H, Carrière F, Fournel A (2010). "Amplitude of pancreatic lipase lid opening in solution and identification of spin label conformational subensembles by combining continuous wave and pulsed EPR spectroscopy and molecular dynamics". Biochemistry. 49 (10): 2140–9. doi:10.1021/bi901918f. PMID 20136147.