fbpx
Wikipedia

Pancreatic lipase family

February 15, 2024

Triglyceride lipases (EC 3.1.1.3) are a family of lipolytic enzymes that hydrolyse ester linkages of triglycerides.[1] Lipases are widely distributed in animals, plants and prokaryotes.

Complex of human pancreatic lipase with colipase
Identifiers
SymbolLipase
PfamPF00151
InterProIPR013818
PROSITEPDOC00110
SCOP21lpa / SCOPe / SUPFAM
OPM superfamily127
OPM protein1lpa
Available protein structures:
Pfam  structures / ECOD  
PDBRCSB PDB; PDBe; PDBj
PDBsumstructure summary

At least three tissue-specific isozymes exist in higher vertebrates, pancreatic, hepatic and gastric/lingual. These lipases are closely related to each other and to lipoprotein lipase (EC 3.1.1.34), which hydrolyses triglycerides of chylomicrons and very low density lipoproteins (VLDL).[2]

The most conserved region in all these proteins is centred on a serine residue which has been shown[3] to participate, with a histidine and an aspartic acid residue, in a charge relay system. Such a region is also present in lipases of prokaryotic origin and in lecithin-cholesterol acyltransferase (EC 2.3.1.43) (LCAT),[4] which catalyzes fatty acid transfer between phosphatidylcholine and cholesterol.

Human pancreatic lipase edit

Pancreatic lipase, also known as pancreatic triacylglycerol lipase or steapsin, is an enzyme secreted from the pancreas. As the primary lipase enzyme that hydrolyzes (breaks down) dietary fat molecules in the human digestive system, it is one of the main digestive enzymes, converting triglyceride substrates like 1 found in ingested oils to monoglycerides 3 and free fatty acids 2a and 2b.[5]

 
Hydrolysis of a triglyceride 1

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.

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.

In humans, pancreatic lipase is encoded by the PNLIP gene.[6][7]

Human proteins containing this domain edit

Diagnostic importance edit

Pancreatic lipase is secreted 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.[8]

Inhibitors edit

Lipase inhibitors such as orlistat can be used as a treatment for obesity.[9]

One peptide selected by phage display was found to inhibit pancreatic lipase.[10]

See also edit

  • Orlistat (a pancreatic lipase inhibitor marketed as an anti-obesity medication)

References edit

  1. ^ Chapus C, Rovery M, Sarda L, Verger R (1988). "Minireview on pancreatic lipase and colipase". Biochimie. 70 (9): 1223–1234. doi:10.1016/0300-9084(88)90188-5. PMID 3147715.
  2. ^ Persson B, Bengtsson-Olivecrona G, Enerback S, Olivecrona T, Jornvall H (1989). "Structural features of lipoprotein lipase. Lipase family relationships, binding interactions, non-equivalence of lipase cofactors, vitellogenin similarities and functional subdivision of lipoprotein lipase". Eur. J. Biochem. 179 (1): 39–45. doi:10.1111/j.1432-1033.1989.tb14518.x. PMID 2917565.
  3. ^ Blow D (1990). "Enzymology. More of the catalytic triad". Nature. 343 (6260): 694–695. Bibcode:1990Natur.343..694B. doi:10.1038/343694a0. PMID 2304545. S2CID 4281247.
  4. ^ McLean J, Fielding C, Drayna D, Dieplinger H, Baer B, Kohr W, Henzel W, Lawn R (1986). "Cloning and expression of human lecithin-cholesterol acyltransferase cDNA". Proc. Natl. Acad. Sci. U.S.A. 83 (8): 2335–2339. Bibcode:1986PNAS...83.2335M. doi:10.1073/pnas.83.8.2335. PMC 323291. PMID 3458198.
  5. ^ Peter Nuhn: Naturstoffchemie, S. Hirzel Wissenschaftliche Verlagsgesellschaft, Stuttgart, 2. Auflage, 1990, S. 308−309, ISBN 3-7776-0473-9.
  6. ^ 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.
  7. ^ "Entrez Gene: pancreatic lipase".
  8. ^ Koop H (September 1984). "Serum levels of pancreatic enzymes and their clinical significance". Clin Gastroenterol. 13 (3): 739–61. doi:10.1016/S0300-5089(21)00756-2. PMID 6207965.
  9. ^ "US orlistat label" (PDF). FDA. August 2015. Retrieved 18 April 2018. For label updates see FDA index page for NDA 020766
  10. ^ Lunder, M.; Bratkovič, T.; Kreft, S.; Štrukelj, B. (2005). "Peptide inhibitor of pancreatic lipase selected by phage display using different elution strategies". Journal of Lipid Research. 46 (7): 1512–1516. doi:10.1194/jlr.M500048-JLR200. PMID 15863836.

Further reading edit

  • Roussel A, Yang Y, Ferrato F, Verger R, Cambillau C, Lowe M (November 1998). "Structure and activity of rat pancreatic lipase-related protein 2". J. Biol. Chem. 273 (48): 32121–8. doi:10.1074/jbc.273.48.32121. PMID 9822688.
  • 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. doi:10.2174/1389203003381487. 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. Bibcode:1993Natur.362..814V. doi:10.1038/362814a0. PMID 8479519. S2CID 4305832.
  • 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. S2CID 28593258.
  • 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. S2CID 39583651.
  • 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.
This article incorporates text from the public domain Pfam and InterPro: IPR013818

February 15, 2024
pancreatic, lipase, family, triglyceride, lipases, family, lipolytic, enzymes, that, hydrolyse, ester, linkages, triglycerides, lipases, widely, distributed, animals, plants, prokaryotes, complex, human, pancreatic, lipase, with, colipaseidentifierssymbollipas. Triglyceride lipases EC 3 1 1 3 are a family of lipolytic enzymes that hydrolyse ester linkages of triglycerides 1 Lipases are widely distributed in animals plants and prokaryotes Complex of human pancreatic lipase with colipaseIdentifiersSymbolLipasePfamPF00151InterProIPR013818PROSITEPDOC00110SCOP21lpa SCOPe SUPFAMOPM superfamily127OPM protein1lpaAvailable protein structures Pfam structures ECOD PDBRCSB PDB PDBe PDBjPDBsumstructure summaryAt least three tissue specific isozymes exist in higher vertebrates pancreatic hepatic and gastric lingual These lipases are closely related to each other and to lipoprotein lipase EC 3 1 1 34 which hydrolyses triglycerides of chylomicrons and very low density lipoproteins VLDL 2 The most conserved region in all these proteins is centred on a serine residue which has been shown 3 to participate with a histidine and an aspartic acid residue in a charge relay system Such a region is also present in lipases of prokaryotic origin and in lecithin cholesterol acyltransferase EC 2 3 1 43 LCAT 4 which catalyzes fatty acid transfer between phosphatidylcholine and cholesterol Contents 1 Human pancreatic lipase 1 1 Human proteins containing this domain 1 2 Diagnostic importance 1 3 Inhibitors 2 See also 3 References 4 Further readingHuman pancreatic lipase editPancreatic lipase also known as pancreatic triacylglycerol lipase or steapsin is an enzyme secreted from the pancreas As the primary lipase enzyme that hydrolyzes breaks down dietary fat molecules in the human digestive system it is one of the main digestive enzymes converting triglyceride substrates like 1 found in ingested oils to monoglycerides 3 and free fatty acids 2a and 2b 5 nbsp Hydrolysis of a triglyceride 1Bile 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 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 In humans pancreatic lipase is encoded by the PNLIP gene 6 7 Human proteins containing this domain edit LIPC LIPG LIPH LIPI LPL PLA1A PNLIP PNLIPRP1 PNLIPRP2 PNLIPRP3Diagnostic importance edit Pancreatic lipase is secreted 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 8 Inhibitors edit Lipase inhibitors such as orlistat can be used as a treatment for obesity 9 One peptide selected by phage display was found to inhibit pancreatic lipase 10 See also editOrlistat a pancreatic lipase inhibitor marketed as an anti obesity medication References edit Chapus C Rovery M Sarda L Verger R 1988 Minireview on pancreatic lipase and colipase Biochimie 70 9 1223 1234 doi 10 1016 0300 9084 88 90188 5 PMID 3147715 Persson B Bengtsson Olivecrona G Enerback S Olivecrona T Jornvall H 1989 Structural features of lipoprotein lipase Lipase family relationships binding interactions non equivalence of lipase cofactors vitellogenin similarities and functional subdivision of lipoprotein lipase Eur J Biochem 179 1 39 45 doi 10 1111 j 1432 1033 1989 tb14518 x PMID 2917565 Blow D 1990 Enzymology More of the catalytic triad Nature 343 6260 694 695 Bibcode 1990Natur 343 694B doi 10 1038 343694a0 PMID 2304545 S2CID 4281247 McLean J Fielding C Drayna D Dieplinger H Baer B Kohr W Henzel W Lawn R 1986 Cloning and expression of human lecithin cholesterol acyltransferase cDNA Proc Natl Acad Sci U S A 83 8 2335 2339 Bibcode 1986PNAS 83 2335M doi 10 1073 pnas 83 8 2335 PMC 323291 PMID 3458198 Peter Nuhn Naturstoffchemie S Hirzel Wissenschaftliche Verlagsgesellschaft Stuttgart 2 Auflage 1990 S 308 309 ISBN 3 7776 0473 9 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 doi 10 1016 S0300 5089 21 00756 2 PMID 6207965 US orlistat label PDF FDA August 2015 Retrieved 18 April 2018 For label updates see FDA index page for NDA 020766 Lunder M Bratkovic T Kreft S Strukelj B 2005 Peptide inhibitor of pancreatic lipase selected by phage display using different elution strategies Journal of Lipid Research 46 7 1512 1516 doi 10 1194 jlr M500048 JLR200 PMID 15863836 Further reading editRoussel A Yang Y Ferrato F Verger R Cambillau C Lowe M November 1998 Structure and activity of rat pancreatic lipase related protein 2 J Biol Chem 273 48 32121 8 doi 10 1074 jbc 273 48 32121 PMID 9822688 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 Carriere 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 Carriere F 2000 The C terminal domain of pancreatic lipase functional and structural analogies with c2 domains Curr Protein Pept Sci 1 1 91 103 doi 10 2174 1389203003381487 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 Vrieze 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 Bibcode 1993Natur 362 814V doi 10 1038 362814a0 PMID 8479519 S2CID 4305832 Lessinger JM Arzoglou P Ramos P Visvikis A Parashou S Calam D Profilis C Ferard 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 S2CID 28593258 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 Piemont E Lessinger JM Bousquet JA Chapus C Kerfelec B Ferard G Mely 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 Carriere 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 S2CID 39583651 Belle V Fournel A Woudstra M Ranaldi S Prieri F Thome V Currault J Verger R Guigliarelli B Carriere 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 Carriere 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 This article incorporates text from the public domain Pfam and InterPro IPR013818 Portal nbsp Biology Retrieved from https en wikipedia org w index php title Pancreatic lipase family amp oldid 1175254269 Human pancreatic lipase, wikipedia, wiki, book, books, library,

article

, read, download, free, free download, mp3, video, mp4, 3gp, jpg, jpeg, gif, png, picture, music, song, movie, book, game, games.