Triglyceride lipases (EC3.1.1.3) are a family of lipolytic enzymes that hydrolyse ester linkages of triglycerides.[1] Lipases are widely distributed in animals, plants and prokaryotes.
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 (EC3.1.1.34), 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 (EC2.3.1.43) (LCAT),[4] which catalyzes fatty acid transfer between phosphatidylcholine and cholesterol.
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 PNLIPgene.[6][7]
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
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
Orlistat (a pancreatic lipase inhibitor marketed as an anti-obesity medication)
^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. PMID6207965.
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. PMID12369922.
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. PMID19113953.
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. PMID8479519. S2CID4305832.
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. PMID12667003. S2CID28593258.
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. PMID18353248.
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. PMID14580194.
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. PMID9631512.
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. PMID8406023.
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. PMID15316225. S2CID39583651.
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. PMID17269661.
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. PMID20136147.
