View source for Lipase

{{Short description|Class of enzymes which cleave fats via hydrolysis}}
[[File:Lipase PLRP2.png|right|thumb|300px|A computer-generated image of a type of pancreatic lipase (PLRP2) from the guinea pig. {{PDB|1GPL}}.]]

In [[biochemistry]], '''lipase''' ({{IPAc-en|ˈ|l|aɪ|p|eɪ|s|,_|ˈ|l|aɪ|p|eɪ|z}} {{respell|LY|payss|,_|LY|payz}}) refers to a class  of [[enzyme]]s that [[catalyze]]s the [[hydrolysis]] of [[fat]]s. Some lipases display broad substrate scope including [[ester]]s of [[cholesterol]], [[phospholipid]]s, and of lipid-soluble [[vitamin]]s<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 [[sphingomyelinase]]s;<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 [[esterase]]s, 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 [[lipid]]s in most, if not all, [[organism]]s.

==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 hydrolase]]s, 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 (chemistry)|substrate]] (A1, A2 or A3). For example, [[human pancreatic lipase]] (HPL),<ref name=Wink/> converts [[triglyceride]] substrates found in ingested oils to [[monoglyceride]]s and two [[fatty acid]]s.

A diverse array of genetically distinct lipase enzymes are found in nature, and they represent several types of [[protein folding|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 |title=Structure of human boob 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><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 [[Diet (nutrition)|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 [[cell (biology)|cell]]s 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 [[Human pancreatic lipase|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 [[phospholipase]]s that enhance the effects of injury and inflammation delivered by a sting.
* As [[biological membrane]]s are integral to living cells and are largely composed of [[phospholipid]]s, 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 [[virus]]es.<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=free }}</ref>

Some lipases are expressed and secreted by pathogenic organisms during an [[infection]]. In particular, ''[[Candida albicans]]'' has many lipases, possibly reflecting broad-[[lipolysis|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|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 [[fat]]s 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://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=278000 Omim – Wolman Disease<!-- Bot generated title -->]</ref>
 |-
 | [[hepatic lipase]] || {{Gene|LIPC}} || [[endothelium]] ||  Hepatic lipase acts on the remaining [[lipid]]s 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 [[triacylglyceride]]s carried on [[Very low-density lipoprotein|VLDL]] (very low density [[lipoprotein]]) so that cells can take up the freed [[fatty acid]]s.  || [[Lipoprotein lipase deficiency]] is caused by [[mutation]]s in the [[gene]] encoding  [[lipoprotein lipase]].<ref>[http://ghr.nlm.nih.gov/condition=lipoproteinlipasedeficiencyfamilial Familial lipoprotein lipase deficiency – Genetics Home Reference<!-- Bot generated title -->]</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 [[mammal]]s.<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 gland]]s ([[Von Ebner's gland|Ebner's gland]]s at the back of the [[tongue]] (lingua), the [[sublingual gland]]s, and the [[parotid gland]]s) || –
|}

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 [[fat]]s 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>

==See also==
* [[Alpha toxin (disambiguation)|Alpha toxin]]
* [[Pathology]]
* [[Lysosomal acid lipase deficiency]]
* [[Peripheral membrane protein]]s
* [[Phospholipase A (disambiguation)|Phospholipase A]]
* [[Phospholipase C]]
* [[Triglyceride lipase]]
* [[Phospholipase A2]]
* [[Outer membrane phospholipase A1]]
* [[Patatin-like phospholipase]]

==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}}

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