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A 'lipase' is a water-soluble enzyme that catalyzes the hydrolysis of ester bonds in water–insoluble, lipid substrates^[1]. Lipases thus comprise a subclass of the esterases.
Lipases are ubiquitous throughout living organisms, and genes encoding lipases are even present in certain viruses. ^[2][3]

Contents

Function

Structure

Location of action

Lipases of Humans

Industrial Uses

Additional images

References

External links

See also

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)^[4], 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 other lipase activities exist in nature, especially when the phospholipases^[5] and sphingomyelinases^[6] are considered.

Structure

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 ^[7][4][9] (see image^[10]) and employ a chymotrypsin-like hydrolysis mechanism involving a serine nucleophile, an acid residue (usually aspartic acid), and a histidine^[11][12].

Location of action

Some lipases work within the interior spaces of living cells to degrade lipids.

★ In the example of lysosomal lipase, the enzyme is confined within an organelle called the lysosome.

★ Other lipase enzymes, such as pancreatic lipases, are found in the spaces outside of cells and have roles in the metabolism, absorption and transport of lipids throughout the body.
As biological membranes are integral to living cells and are largely composed of phospholipids, lipases play important roles in cell biology.
Furthermore, lipases are involved in diverse biological processes ranging from routine metabolism of dietary triglycerides to cell signaling^[13] and inflammation^[14].

Lipases of Humans

The main lipases in 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).

'Name'	'Gene'	'Description'	'Disorder'
pancreatic lipase		In order to exhibit optimal enzyme activity in the gut lumen, HPL requires another protein, colipase, which is also secreted by the pancreas[15].	-
lysosomal lipase		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.[16]
hepatic lipase		Hepatic lipase acts on the remaining lipids carried on lipoproteins in the blood to regenerate LDL (low density lipoprotein).	-
lipoprotein lipase	or "LIPD"	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.[17] [18]
hormone-sensitive lipase		-	-
gastric lipase		Functions in the infant at a near-neutral pH to aid in the digestion of lipids	-
endothelial lipase		-	-
pancreatic lipase related protein 2	or "PLRP2"	-	-
pancreatic lipase related protein 1	or "PLRP1"	Pancreatic lipase related protein 1 is very similar to PLRP2 and HPL 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[19][20].	-

Other lipases include , , , , , and .
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 ^[21] in alternative energy strategies to convert vegetable oil into fuel. ^[22][23]

Additional images

References

1. Lipase protein engineering, Svendsen A, , , Biochim Biophys Acta, 2000
2. The genome of Melanoplus sanguinipes entomopoxvirus, Afonso C, Tulman E, Lu Z, Oma E, Kutish G, Rock D, , , J Virol, 1999
3. The VP1 capsid protein of adeno-associated virus type 2 is carrying a phospholipase A2 domain required for virus infectivity, Girod A, Wobus C, Zádori Z, Ried M, Leike K, Tijssen P, Kleinschmidt J, Hallek M, , , J Gen Virol, 2002
4. Structure of human pancreatic lipase, Winkler FK, D'Arcy A, and W Hunziker, , , Nature, 1990
5. Phospholipase A(2)., Diaz, B.L., and J. P. Arm., , , Prostaglandins Leukot Essent Fatty Acids, 2003
6. Sphingomyelinases: enzymology and membrane activity, Goñi F, Alonso A, , , FEBS Lett, 2002
7. Lipases and alpha/beta hydrolase fold, Schrag J, Cygler M, , , Methods Enzymol,
8. Structure of human pancreatic lipase, Winkler FK, D'Arcy A, and W Hunziker, , , Nature, 1990
9. Impact of Structural Information on Understanding of Lipolytic Function, Egmond, M. R., and C. J. van Bemmel, , , Methods Enzymol, 1997
10. A pancreatic lipase with a phospholipase A1 activity: crystal structure of a chimeric pancreatic lipase-related protein 2 from guinea pig, Withers-Martinez C, Carriere F, Verger R, Bourgeois D, and C Cambillau, , , Structure, 1996
11. A serine protease triad forms the catalytic centre of a triacylglycerol lipase., 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., , , Nature, 1990
12. The catalytic site residues and interfacial binding of human pancreatic lipase, Lowe ME, , , J Biol Chem, 1992
13. Signal transduction through lipid second messengers, Spiegel S, Foster D, and R Kolesnick, , , Curr Opin Cell Biol, 1996
14. Plasma platelet-activating factor acetylhydrolase is a secreted phospholipase A2 with a catalytic triad, Tjoelker LW, Eberhardt C, Unger J, Trong HL, Zimmerman GA, McIntyre TM, Stafforini DM, Prescott SM, and PW Gray, , , J Biol Chem, 1995
15. The triglyceride lipases of the pancreas, Lowe ME, , , J Lipid Res, 2002
16. http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=278000
17. http://ghr.nlm.nih.gov/condition=lipoproteinlipasedeficiencyfamilial
18. 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, Gilbert B, Rouis M, Griglio S, de Lumley L, Laplaud P, , , Ann Genet,
19. Pancreatic lipase-related protein type I: a specialized lipase or an inactive enzyme, Crenon I, Foglizzo E, Kerfelec B, Verine A, Pignol D, Hermoso J, Bonicel J, Chapus C, , , Protein Eng, 1998
20. Pancreatic lipase-related protein 1 (PLRP1) is present in the pancreatic juice of several species, De Caro J, Carriere F, Barboni P, Giller T, Verger R, De Caro A, , , Biochim Biophys Acta, 1998
21. New opportunity for enzymatic modification of fats and oils with industrial potentials., Guo Z, Xu X, , , Org Biomol Chem, 2005
22. Bacterial lipases: an overview of production, purification and biochemical properties, Gupta R, Gupta N, Rathi P, , , Appl Microbiol Biotechnol, 2004
23. Whole cell biocatalyst for biodiesel fuel production utilizing Rhizopus oryzae cells immobilized within biomass support particles, Ban K, Kaieda M, Matsumoto T, Kondo A, Fukuda H, , , Biochem Eng J, 2001

External links

★

★ 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)

See also

★ Phospholipase A

★ Phospholipase C

★ Alpha toxin

★ Peripheral membrane proteins