Lipase

A lipase is a water-soluble enzyme that catalyzes the hydrolysis of ester bonds in water–insoluble, lipid substrates [cite journal |author=Svendsen A |title=Lipase protein engineering |journal=Biochim Biophys Acta |volume=1543 |issue=2 |pages=223–228 |year=2000 |pmid=11150608] . Lipases thus comprise a subclass of the esterases.

Lipases perform essential roles in the digestion, transport and processing of dietary lipids (e.g. triglycerides, fats, oils) in most- if not all- living organisms. Genes encoding lipases are even present in certain viruses. [cite journal |author=Afonso C, Tulman E, Lu Z, Oma E, Kutish G, Rock D |title=The genome of Melanoplus sanguinipes entomopoxvirus |journal=J Virol |volume=73 |issue=1 |pages=533–52 |year=1999 |pmid=9847359] [cite journal |author=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]

Function

Most lipases act at a specific position on the glycerol backbone of a lipid substrate (A₁, A₂ or A₃).

In the example of human pancreatic lipase (HPL) [cite journal |author=Winkler FK, D'Arcy A, and 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] , which is the main enzyme responsible for breaking down fats in the human digestive system, a lipase acts to convert triglyceride substrates found in oils from food to monoglycerides and free fatty acids.

Myriad of other lipase activities exist in nature, especially when the phospholipases [cite journal |author=Diaz, B.L., and J. P. Arm. |title=Phospholipase A(2) |journal=Prostaglandins Leukot Essent Fatty Acids |volume=2-3 |pages=87–97|year=2003 |pmid=12895591 |doi=10.1016/S0952-3278(03)00069-3] and sphingomyelinases [cite journal |author=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] are considered.

tructure

While a diverse array of genetically distinct lipase enzymes are found in nature, and represent several types of protein folds and catalytic mechanisms, most are built on an alpha/beta hydrolase fold [cite journal |author=Schrag J, Cygler M |title=Lipases and alpha/beta hydrolase fold |journal=Methods Enzymol |volume=284 |issue= |pages=85–107 |year= 1997|pmid=9379946 |doi=10.1016/S0076-6879(97)84006-2] [cite journal |author=Winkler FK, D'Arcy A, and 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] [cite journal |author=Egmond, M. R., and C. J. van Bemmel |title=Impact of Structural Information on Understanding of Lipolytic Function |journal=Methods Enzymol |volume=284 |pages=119–129 |year= 1997 |pmid=9379930 |doi=10.1016/S0076-6879(97)84008-6] (see image [cite journal |author=Withers-Martinez C, Carriere F, Verger R, Bourgeois D, and 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] ) and employ a chymotrypsin-like hydrolysis mechanism involving a serine nucleophile, an acid residue (usually aspartic acid), and a histidine [cite journal |author=Brady, L., A. M. Brzozowski, Z. S. Derewenda, E. Dodson, G. Dodson, S. Tolley, J. P. Turkenburg, L. Christiansen, B. Huge-Jensen, L. Norskov, and et al. |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] [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 |pmid=1512245] .

Physiological distribution

Lipases are involved in diverse biological processes ranging from routine metabolism of dietary triglycerides to cell signaling [cite journal |author=Spiegel S, Foster D, and R Kolesnick|title=Signal transduction through lipid second messengers|journal=Curr Opin Cell Biol|volume=8|issue=2 |pages=159–67 |year=1996 |pmid=8791422 |doi=10.1016/S0955-0674(96)80061-5] and inflammation [cite journal |author=Tjoelker LW, Eberhardt C, Unger J, Trong HL, Zimmerman GA, McIntyre TM, Stafforini DM, Prescott SM, and 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] . 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 "biological payload" 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.

Lipases of humans

The main lipases of the human digestive system are human pancreatic lipase (HPL) and pancreatic lipase related protein 2 (PLRP2), which are secreted by the pancreas. Humans also have several other related enzymes, including hepatic lipase (HL), endothelial lipase, and lipoprotein lipase. Not all of these lipases function in the gut (see table).

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

There also are a diverse array of phospholipases, but these are not always classified with the other lipases.

Industrial Uses

Lipases from fungi and bacteria serve important roles in human practices as ancient as yogurt and cheese fermentation. However, lipases are also being exploited as cheap and versatile catalysts to degrade lipids in more modern applications. For instance, a biotechnology company has brought recombinant lipase enzymes to market for use in applications such as baking, laundry detergents and even as biocatalysts [cite journal |author=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] in alternative energy strategies to convert vegetable oil into fuel. [cite journal |author=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] [cite journal |author=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]

=Additional

References

External links

*
* [http://logikbase.com/website/techprofile.cfm?licid=940 Selective Inhibitors of Monoacylglycerol Lipase as a Treatment for Neurological Disorders 2004-637]
* - Phospholipases A2
* - Outer membrane phospholipase A
* - Cytosolic phospholipase A2 and patatin
* - Bacterial and mammalian phospolipases C
* - α-toxin (a bacterial phospholipase C)

ee also

*Triglyceride lipase
*Phospholipase A
*Phospholipase C
*Alpha toxin
*Peripheral membrane proteins