Pancreatic lipase

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
Gene location (Human)
Chr.	Chromosome 10 (human)
End	116,567,855 bp
Gene location (Mouse)
Chr.	Chromosome 19 (mouse)
End	58,670,220 bp
RNA expression pattern
	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
	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
	5406
	69060
	ENSG00000175535
	ENSMUSG00000046008
	P16233
	Q6P8U6
	NM_000936
	NM_026925
	NP_000927
	NP_081201
	Wikidata
View/Edit Human	View/Edit Mouse

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

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.

References

1 2 3 GRCh38: Ensembl release 89: ENSG00000175535 – Ensembl, May 2017
1 2 3 GRCm38: Ensembl release 89: ENSMUSG00000046008 – Ensembl, May 2017
↑ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
↑ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
↑ Davis RC, Diep A, Hunziker W, Klisak I, Mohandas T, Schotz MC, Sparkes RS, Lusis AJ (December 1991). "Assignment of human pancreatic lipase gene (PNLIP) to chromosome 10q24-q26". Genomics. 11 (4): 1164–6. doi:10.1016/0888-7543(91)90048-J. PMID 1783385.
↑ "Entrez Gene: pancreatic lipase".
↑ Koop H (September 1984). "Serum levels of pancreatic enzymes and their clinical significance". Clin Gastroenterol. 13 (3): 739–61. PMID 6207965.
↑ "US orlistat label" (PDF). FDA. August 2015. Archived from the original (PDF) on February 28, 2017. Retrieved 18 April 2018. For label updates see FDA index page for NDA 020766

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.

[refGRCh38Ensembl-1] 1 2 3 GRCh38: Ensembl release 89: ENSG00000175535 – Ensembl, May 2017

[refGRCm38Ensembl-2] 1 2 3 GRCm38: Ensembl release 89: ENSMUSG00000046008 – Ensembl, May 2017

[3] "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.

[4] "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.

[pmid1783385-5] Davis RC, Diep A, Hunziker W, Klisak I, Mohandas T, Schotz MC, Sparkes RS, Lusis AJ (December 1991). "Assignment of human pancreatic lipase gene (PNLIP) to chromosome 10q24-q26". Genomics. 11 (4): 1164–6. doi:10.1016/0888-7543(91)90048-J. PMID 1783385.

[entrez-6] "Entrez Gene: pancreatic lipase".

[pmid6207965-7] Koop H (September 1984). "Serum levels of pancreatic enzymes and their clinical significance". Clin Gastroenterol. 13 (3): 739–61. PMID 6207965.

[USlabel-8] "US orlistat label" (PDF). FDA. August 2015. Archived from the original (PDF) on February 28, 2017. Retrieved 18 April 2018. For label updates see FDA index page for NDA 020766

v t e Enzymes
Activity	Active site Binding site Catalytic triad Oxyanion hole Enzyme promiscuity Diffusion-limited enzyme Cofactor Enzyme catalysis
Regulation	Allosteric regulation Cooperativity Enzyme inhibitor Enzyme activator
Classification	EC number Enzyme superfamily Enzyme family List of enzymes
Kinetics	Enzyme kinetics Eadie–Hofstee diagram Hanes–Woolf plot Lineweaver–Burk plot Michaelis–Menten kinetics
Types	EC1 Oxidoreductases (list) EC2 Transferases (list) EC3 Hydrolases (list) EC4 Lyases (list) EC5 Isomerases (list) EC6 Ligases (list) EC7 Translocases (list)