Lipase

{{Short description|Class of enzymes which cleave fats via hydrolysis}} {{Distinguish|Ligase}} {{Infobox diagnostic | name = Lipase | image = Lipase PLRP2.png | alt = | caption = A computer-generated image of a type of pancreatic lipase (PLRP2) from the guinea pig. {{PDB|1GPL}} | pronounce = {{IPAc-en|ˈ|l|aɪ|p|eɪ|s|,_|ˈ|l|aɪ|p|eɪ|z}} {{respell|LY|payss|,_|LY|payz}} | purpose = | test of = Pancreatitis | based on = | synonyms = | reference_range = | DiseasesDB =  | ICD10 =  | ICD9 = | ICDO = | MedlinePlus =  | eMedicine =  | MeshID = | OPS301 =  | LOINC =  | calculator = {{Lipase conversion}} | video1 = }} '''Lipase''' is a class of enzymes that catalyzes the hydrolysis of fats. Some lipases display broad substrate scope including esters of cholesterol, phospholipids, and of lipid-soluble vitamins<ref name=bile/><ref>{{cite journal |author1=Diaz, B.L. |author2=J. P. Arm. |title=Phospholipase A(2) |journal=Prostaglandins Leukot Essent Fatty Acids |volume= 69|pages=87–97|year=2003 |pmid=12895591 |doi=10.1016/S0952-3278(03)00069-3 |issue=2–3}}</ref> and sphingomyelinases;<ref>{{cite journal |vauthors=Goñi F, Alonso A |title=Sphingomyelinases: enzymology and membrane activity |journal=FEBS Lett |volume=531 |issue=1 |pages=38–46 |year=2002 |pmid=12401200 |doi=10.1016/S0014-5793(02)03482-8|doi-access= |bibcode=2002FEBSL.531...38G }}</ref> however, these are usually treated separately from "conventional" lipases. Unlike esterases, which function in water, lipases "are activated only when adsorbed to an oil–water interface".<ref name=Sharma>{{cite journal |doi=10.1016/S0734-9750(01)00086-6|title=Production, purification, characterization, and applications of lipases|year=2001|last1=Sharma|first1=Rohit|last2=Chisti|first2=Yusuf|last3=Banerjee|first3=Uttam Chand|journal=Biotechnology Advances|volume=19|issue=8|pages=627–662|pmid=14550014|s2cid=18615547 |citeseerx=10.1.1.319.7729}}</ref> Lipases perform essential roles in digestion, transport and processing of dietary lipids in most, if not all, organisms.

==Structure and catalytic mechanism== Classically, lipases catalyse the hydrolysis of triglycerides:{{cn|date=January 2025}} <math chem display=block>\begin{align} \text{triglyceride} + \ce{H2O} &\longrightarrow \text{fatty acid} + \text{diacylglycerol} \\[4pt] \text{diacylglycerol} + \ce{H2O} &\longrightarrow \text{fatty acid} + \text{monacylglycerol} \\[4pt] \text{monacylglycerol} + \ce{H2O} &\longrightarrow \text{fatty acid} + \text{glycerol} \end{align}</math>

Lipases are serine hydrolases, i.e. they function by transesterification generating an acyl serine intermediate. Most lipases act at a specific position on the glycerol backbone of a lipid substrate (A1, A2 or A3). For example, human pancreatic lipase (HPL),<ref name=Wink/> converts triglyceride substrates found in ingested oils to monoglycerides and two fatty acids.

A diverse array of genetically distinct lipase enzymes are found in nature, and they represent several types of protein folds and catalytic mechanisms. However, most are built on an alpha/beta hydrolase fold<ref name="Winkler FK, D'Arcy A, and W Hunziker 1990 771–774">{{cite journal |author1=Winkler FK |author2=D'Arcy A |author3=W Hunziker |year=1990 |title=Structure of human pancreatic lipase |journal=Nature |volume=343 |issue=6260 |pages=771–774 |bibcode=1990Natur.343..771W |doi=10.1038/343771a0 |pmid=2106079 |s2cid=37423900}}</ref><ref>{{cite book |vauthors=Schrag J, Cygler M |chapter=Lipases and hydrolase fold |title=Lipases, Part A: Biotechnology |volume=284 |pages=85–107 |year= 1997|pmid=9379946 |doi=10.1016/S0076-6879(97)84006-2 |series=Methods in Enzymology |isbn=978-0-12-182185-2}}</ref><ref>{{cite book |author1=Egmond, M. R. |author2=C. J. van Bemmel |chapter=Impact of structural information on understanding lipolytic function |title=Lipases, Part A: Biotechnology |volume=284 |pages=119–129 |year= 1997 |pmid=9379930 |doi=10.1016/S0076-6879(97)84008-6 |series=Methods in Enzymology |isbn=978-0-12-182185-2}}</ref><ref>{{cite journal |author1=Withers-Martinez C |author2=Carriere F |author3=Verger R |author4=Bourgeois D |author5=C Cambillau |title=A pancreatic lipase with a phospholipase A1 activity: crystal structure of a chimeric pancreatic lipase-related protein 2 from guinea pig|journal=Structure|volume=4|issue=11 |pages= 1363–74 |year=1996 |pmid=8939760|doi=10.1016/S0969-2126(96)00143-8|doi-access=free }}</ref> and employ a chymotrypsin-like hydrolysis mechanism using a catalytic triad consisting of a serine nucleophile, a histidine base, and an acid residue, usually aspartic acid.<ref>{{cite journal |author=Brady, L. |author2=A. M. Brzozowski |author3=Z. S. Derewenda |author4=E. Dodson |author5=G. Dodson |author6=S. Tolley |author7=J. P. Turkenburg |author8=L. Christiansen |author9=B. Huge-Jensen |author10=L. Norskov |title=A serine protease triad forms the catalytic centre of a triacylglycerol lipase |journal=Nature |volume=343 |issue=6260 |pages=767–70 |year=1990 |pmid=2304552 |doi=10.1038/343767a0|bibcode=1990Natur.343..767B |s2cid=4308111 |display-authors=etal}}</ref><ref>{{cite journal |author=Lowe ME |title=The catalytic site residues and interfacial binding of human pancreatic lipase |journal=J Biol Chem |volume=267 |issue=24 |pages=17069–73 |year=1992 |doi=10.1016/S0021-9258(18)41893-5 |pmid=1512245|doi-access=free }}</ref>

==Physiological distribution== Lipases are involved in diverse biological processes which range from routine metabolism of dietary triglycerides to cell signaling<ref>{{cite journal |author1=Spiegel S |author2=Foster D |author3=R Kolesnick |title=Signal transduction through lipid second messengers|journal=Current Opinion in Cell Biology|volume=8|issue=2 |pages=159–67 |year=1996 |pmid=8791422 |doi=10.1016/S0955-0674(96)80061-5|doi-access=free }}</ref> and inflammation.<ref>{{cite journal |author1=Tjoelker LW |author2=Eberhardt C |author3=Unger J |author4=Trong HL |author5=Zimmerman GA |author6=McIntyre TM |author7=Stafforini DM |author8=Prescott SM |author9=PW Gray |title=Plasma platelet-activating factor acetylhydrolase is a secreted phospholipase A2 with a catalytic triad |journal=J Biol Chem |volume=270 |issue=43 |pages=25481–7 |year=1995 |pmid=7592717 |doi=10.1074/jbc.270.43.25481|doi-access=free }}</ref> Thus, some lipase activities are confined to specific compartments within cells while others work in extracellular spaces. * In the example of lysosomal lipase, the enzyme is confined within an organelle called the lysosome. * Other lipase enzymes, such as pancreatic lipases, are secreted into extracellular spaces where they serve to process dietary lipids into more simple forms that can be more easily absorbed and transported throughout the body. * Fungi and bacteria may secrete lipases to facilitate nutrient absorption from the external medium (or in examples of pathogenic microbes, to promote invasion of a new host). * Certain wasp and bee venoms contain phospholipases that enhance the effects of injury and inflammation delivered by a sting. * As biological membranes are integral to living cells and are largely composed of phospholipids, lipases play important roles in cell biology. * ''Malassezia globosa'', a fungus thought to be the cause of human dandruff, uses lipase to break down sebum into oleic acid and increase skin cell production, causing dandruff.<ref>[http://news.bbc.co.uk/2/hi/health/7080434.stm Genetic Code of Dandruff Cracked – BBC News]</ref>

Genes encoding lipases are even present in certain viruses.<ref>{{cite journal |vauthors=Afonso C, Tulman E, Lu Z, Oma E, Kutish G, Rock D |title=The Genome of Melanoplus sanguinipes Entomologists |journal=J Virol |volume=73 |issue=1 |pages=533–52 |year=1999 |doi=10.1128/JVI.73.1.533-552.1999 |pmid=9847359 |pmc=103860}}</ref><ref>{{cite journal |vauthors=Girod A, Wobus C, Zádori Z, Ried M, Leike K, Tijssen P, Kleinschmidt J, Hallek M |title=The VP1 capsid protein of adeno-associated virus type 2 is carrying a phospholipase A2 domain required for virus infectivity |journal=J Gen Virol |volume=83 |issue=Pt 5 |pages=973–8 |year=2002 |pmid=11961250 |doi=10.1099/0022-1317-83-5-973|doi-access= }}</ref>

Some lipases are expressed and secreted by pathogenic organisms during an infection. In particular, ''Candida albicans'' has many lipases, possibly reflecting broad-lipolytic activity, which may contribute to the persistence and virulence of ''C. albicans ''in human tissue.<ref>{{cite journal |vauthors=Hube B, Stehr F, Bossenz M, Mazur A, Kretschmar M, Schafer W |title=Secreted lipases of Candida albicans: cloning, characterisation and expression analysis of a new gene family with at least ten members |journal=Arch. Microbiol. |volume=174 |issue=5 |pages=362–374 |year=2000 |pmid=11131027 |doi=10.1007/s002030000218|bibcode=2000ArMic.174..362H |s2cid=2231039 }}</ref>

===Human lipases===

{| class="wikitable" ! Name !! Gene !! Location !! Description !! Disorder |- | bile salt-dependent lipase || BSDL || pancreas, breast milk || aids in the digestion of fats<ref name=bile>{{cite journal |doi=10.1016/S1388-1981(01)00130-5|title=Bile salt-dependent lipase: its pathophysiological implications|year=2001|last1=Lombardo|first1=Dominique|journal=Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of Lipids|volume=1533|issue=1 |pages=1–28|pmid=11514232}}</ref> || |- | pancreatic lipase || {{Gene|PNLIP}} || digestive juice || Human pancreatic lipase (HPL) is the main enzyme that breaks down dietary fats in the human digestive system.<ref name=Wink>{{cite journal |author1=Winkler FK |author2=D'Arcy A |author3=W Hunziker |title=Structure of human pancreatic lipase |journal=Nature|volume=343 |issue=6260 |pages=771–774 |year= 1990 |pmid=2106079 |doi=10.1038/343771a0|bibcode=1990Natur.343..771W |s2cid=37423900 }}</ref> To exhibit optimal enzyme activity in the gut lumen, PL requires another protein, colipase, which is also secreted by the pancreas.<ref>{{cite journal |author=Lowe ME |title=The triglyceride lipases of the pancreas |journal= J Lipid Res |volume=43 |issue=12 |pages=2007–16 |year=2002 |pmid=12454260 |doi=10.1194/jlr.R200012-JLR200 |doi-access= free}}</ref> || |- | lysosomal lipase || {{Gene|LIPA}} || interior space of organelle: lysosome || Also referred to as lysosomal acid lipase (LAL or LIPA) or acid cholesteryl ester hydrolase || Cholesteryl ester storage disease (CESD) and Wolman disease are both caused by mutations in the gene encoding lysosomal lipase.<ref>[https://web.archive.org/web/20090509200200/http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=278000 Omim – Wolman Disease]</ref> |- | hepatic lipase || {{Gene|LIPC}} || endothelium || Hepatic lipase acts on the remaining lipids carried on lipoproteins in the blood to regenerate LDL (low density lipoprotein). || – |- | lipoprotein lipase || {{Gene|LPL}} or "LIPD" || endothelium || Lipoprotein lipase functions in the blood to act on triacylglycerides carried on VLDL (very low density lipoprotein) so that cells can take up the freed fatty acids. || Lipoprotein lipase deficiency is caused by mutations in the gene encoding lipoprotein lipase.<ref>[https://archive.today/20120708111635/http://ghr.nlm.nih.gov/condition=lipoproteinlipasedeficiencyfamilial Familial lipoprotein lipase deficiency – Genetics Home Reference]</ref><ref>{{cite journal |vauthors=Gilbert B, Rouis M, Griglio S, de Lumley L, Laplaud P |title=Lipoprotein lipase (LPL) deficiency: a new patient homozygote for the preponderant mutation Gly188Glu in the human LPL gene and review of reported mutations: 75 % are clustered in exons 5 and 6 |journal=Ann Genet |volume=44 |issue=1 |pages=25–32 |year= 2001|pmid=11334614 |doi=10.1016/S0003-3995(01)01037-1}}</ref> |- | hormone-sensitive lipase || {{Gene|LIPE}} || intracellular || – || – |- | gastric lipase || {{Gene|LIPF}} || digestive juice || Functions in the infant at a near-neutral pH to aid in the digestion of lipids || – |- | endothelial lipase || {{Gene|LIPG}} || endothelium || – || – |- | pancreatic lipase related protein 2 || {{Gene|PNLIPRP2}} or "PLRP2" – || digestive juice|| – || – |- | pancreatic lipase related protein 1 || {{Gene|PNLIPRP1}} or "PLRP1" || digestive juice|| Pancreatic lipase related protein 1 is very similar to PLRP2 and PL by amino acid sequence (all three genes probably arose via gene duplication of a single ancestral pancreatic lipase gene). However, PLRP1 is devoid of detectable lipase activity and its function remains unknown, even though it is conserved in other mammals.<ref>{{cite journal |vauthors=Crenon I, Foglizzo E, Kerfelec B, Verine A, Pignol D, Hermoso J, Bonicel J, Chapus C |title=Pancreatic lipase-related protein type I: a specialized lipase or an inactive enzyme|journal=Protein Eng|volume=11|issue=2 |pages= 135–42 |year=1998 |pmid=9605548 |doi=10.1093/protein/11.2.135|doi-access=free }}</ref><ref>{{cite journal |vauthors=De Caro J, Carriere F, Barboni P, Giller T, Verger R, De Caro A |title=Pancreatic lipase-related protein 1 (PLRP1) is present in the pancreatic juice of several species|journal=Biochim Biophys Acta|volume=1387|issue=1–2 |pages= 331–41 |year=1998 |pmid=9748646 |doi=10.1016/S0167-4838(98)00143-5}}</ref> || - |- | lingual lipase || ? || saliva || Active at gastric pH levels. Optimum pH is about 3.5-6. Secreted by several of the salivary glands (Ebner's glands at the back of the tongue (lingua), the sublingual glands, and the parotid glands) || – |}

Other lipases include {{Gene|LIPH}}, {{Gene|LIPI}}, {{Gene|LIPJ}}, {{Gene|LIPK}}, {{Gene|LIPM}}, {{Gene|LIPN}}, {{Gene|MGLL}}, {{Gene|DAGLA}}, {{Gene|DAGLB}}, and {{Gene|CEL}}.

==Uses== In the commercial sphere, lipases are widely used in laundry detergents. Several thousand tons per year are produced for this role.<ref name=Sharma/>

Lipases are catalysts for hydrolysis of esters and are useful outside of the cell, a testament to their wide substrate scope and ruggedness. The ester hydrolysis activity of lipases has been well evaluated for the conversion of triglycerides into biofuels or their precursors.<ref>{{cite journal |vauthors=Gupta R, Gupta N, Rathi P |title=Bacterial lipases: an overview of production, purification and biochemical properties|journal=Appl Microbiol Biotechnol|volume=64|issue=6 |pages=763–81 |year=2004 |pmid=14966663 |doi=10.1007/s00253-004-1568-8|s2cid=206934353}}</ref><ref>{{cite journal |vauthors=Ban K, Kaieda M, Matsumoto T, Kondo A, Fukuda H |title=Whole cell biocatalyst for biodiesel fuel production utilizing ''Rhizopus oryzae'' cells immobilized within biomass support particles|journal=Biochem Eng J|volume=8|issue=1|pages=39–43|year=2001|pmid=11356369 |doi=10.1016/S1369-703X(00)00133-9|bibcode=2001BioEJ...8...39B }}</ref><ref>{{cite journal |doi=10.1016/j.jclepro.2007.07.003 |title=A life-cycle comparison between inorganic and biological catalysis for the production of biodiesel |journal=Journal of Cleaner Production |volume=16 |issue=13 |pages=1368–78 |year=2008 |last1=Harding |first1=K.G |last2=Dennis |first2=J.S |last3=von Blottnitz |first3=H |last4=Harrison |first4=S.T.L |bibcode=2008JCPro..16.1368H }}</ref><ref>{{cite journal |vauthors=Guo Z, Xu X |title=New opportunity for enzymatic modification of fats and oils with industrial potentials|journal=Org Biomol Chem|volume=3|issue=14 |pages=2615–9 |year=2005 |pmid=15999195 |doi=10.1039/b506763d}}</ref>

Lipases are chiral, which means that they can be used for the enantioselective hydrolysis prochiral diesters.<ref>{{cite journal|doi=10.1021/cr00038a017|title=Lipase-Supported Synthesis of Biologically Active Compounds|year=1995|last1=Theil|first1=Fritz|journal=Chemical Reviews|volume=95|issue=6|pages=2203–2227}}</ref> Several procedures have been reported for applications in the synthesis of fine chemicals.<ref>{{cite journal|journal=Org. Synth.|year=1990|volume=69|page=10|doi=10.15227/orgsyn.069.0010|title=Enantiomerically Pure Ethyl (R)- And (S)- 2-Fluorohexanoate by Enzyme-Catalyzed Kinetic Resolution|author=P. Kalaritis, R. W. Regenye}}</ref><ref>{{cite journal |title=(4R)-(+)-tert-Butyldimethylsiloxy-2-cyclopenten-1-one|author= Leo A. Paquette, Martyn J. Earle, Graham F. Smith|journal=Org. Synth.|year=1996|volume=73|page=36|doi=10.15227/orgsyn.073.0036}}</ref><ref>{{cite journal|doi=10.15227/orgsyn.073.0036|title=(4R)-(+)-tert-BUTYLDIMETHYLSILOXY-2-CYCLOPENTEN-1-ONE |journal=Organic Syntheses |year=1996 |volume=73 |page=36 }}</ref>

Lipases are generally animal sourced, but can also be sourced microbially.{{citation needed|date=May 2020}}

===Biomedicine=== Blood tests for lipase may be used to help investigate and diagnose acute pancreatitis and other disorders of the pancreas.<ref>{{cite web|title=Lipase – TheTest|url=http://labtestsonline.org/understanding/analytes/lipase/tab/test/|work=Lab Tests Online|access-date=12 May 2014}}</ref> Measured serum lipase values may vary depending on the method of analysis.{{Citation needed|date=January 2021}}

Lipase assist in the breakdown of fats in those undergoing pancreatic enzyme replacement therapy (PERT). It is a component in Sollpura (Liprotamase).<ref>"Anthera Pharmaceuticals – Sollpura." Anthera Pharmaceuticals – Sollpura. N.p., n.d. Web. 21 July 2015. <http://www.anthera.com/pipeline/science/sollpura.html {{Webarchive|url=https://web.archive.org/web/20150718042137/http://www.anthera.com/pipeline/science/sollpura.html |date=2015-07-18 }}>.</ref><ref>{{cite journal |doi=10.3109/14756366.2010.525509 |pmid=21028941 |title=Pancreatic lipase inhibition activity of trilactone terpenes of ''Ginkgo biloba'' |journal=Journal of Enzyme Inhibition and Medicinal Chemistry |volume=26 |issue=4 |pages=453–9 |year=2010 |last1=Bustanji |first1=Yasser |last2=Al-Masri |first2=Ihab M |last3=Mohammad |first3=Mohammad |last4=Hudaib |first4=Mohammad |last5=Tawaha |first5=Khaled |last6=Tarazi |first6=Hamada |last7=Alkhatib |first7=Hatim S |s2cid=23597738 |doi-access=free }}</ref>

==References== {{Reflist|2}}

25. Gulzar, Bio-degradation of hydrocarbons using different bacterial and fungal species. Published in international conference on biotechnology and neurosciences. CUSAT (cochin university of science and technology), 2003

==External links== * {{MeshName|Lipase}}

Category:Hydrolases Category:Peripheral membrane proteins Category:EC 3.1