A is a Water-soluble Enzyme that Catalyze s the Hydrolysis of Ester Bonds in water–insoluble, Lipid substrates. 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), 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 mono Glyceride s and free Fatty Acid s. Myriad other lipase activities exist in nature, especially when the Phospholipase s and Sphingomyelinase s are considered.
Lipases are ubiquitous throughout living Organism s, and Genes encoding lipases are even present in certain Virus es. While a diverse array of Genetic ally distinct lipase enzymes are found in nature, and represent distinct types of Protein Folds and catalytic mechanisms, most are built on an alpha/beta hydrolase fold (see image) and employ a Chymotrypsin -like hydrolysis mechanism involving a Serine Nucleophile , an Acid residue (usually Aspartic Acid ), and a Histidine .
Some lipases work within the interior spaces of living Cell s 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 Membrane s are integral to living cells and are largely composed of Phospholipid s, 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 and Inflammation . Several different types of lipases are found in the human Body , including pancreatic lipase, hepatic lipase, lysosomal lipase, gastric lipase, endothelial lipase, as well as various different phospholipases.
At least three human (CESD) and Wolman Disease are both caused by mutations in the gene encoding lysosomal lipase, also referred to as lysosomal acid lipase (LAL or LIPA) or acid cholesteryl ester hydrolase {Link without Title} .
- Afonso, C. L., E. R. Tulman, Z. Lu, E. Oma, G. F. Kutish, and D. L. Rock. 1999. The genome of Melanoplus sanguinipes entomopoxvirus. ''J Virol'' 73:533-52.
- 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. 1990. A serine protease triad forms the catalytic centre of a triacylglycerol lipase. ''Nature'' 343:767-70.
- Carriere, F., C. Withers-Martinez, H. van Tilbeurgh, A. Roussel, C. Cambillau, and R. Verger. 1998. Structural basis for the substrate selectivity of pancreatic lipases and some related proteins. ''Biochim Biophys Acta'' 1376:417-32.
- Diaz, B. L., and J. P. Arm. 2003. Phospholipase A(2). ''Prostaglandins Leukot Essent Fatty Acids'' 69:87-97.
- Egmond, M. R., and C. J. van Bemmel. 1997. Impact of Structural Information on Understanding of Lipolytic Function, p. 119-129, ''Methods Enzymol'' vol. 284.
- Gilbert B, Rouis M, Griglio S, de Lumley L, Laplaud P. 2001. 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. ''Ann Genet'' 44(1):25-32.
- Girod, A., C. E. Wobus, Z. Zadori, M. Ried, K. Leike, P. Tijssen, J. A. Kleinschmidt, and M. Hallek. 2002. The VP1 capsid protein of adeno-associated virus type 2 is carrying a phospholipase A2 domain required for virus infectivity. J ''Gen Virol'' 83:973-8.
- Goni FM, Alonso A. 2002 Sphingomyelinases: enzymology and membrane activity. ''FEBS Lett''. 531(1):38-46.
- Heikinheimo, P., A. Goldman, C. Jeffries, and D. L. Ollis. 1999. Of barn owls and bankers: a lush variety of alpha/beta hydrolases. ''Structure Fold Des'' 7:R141-6.
- Lowe, M. E. 1992. The catalytic site residues and interfacial binding of human pancreatic lipase. ''J Biol Chem'' 267:17069-73.
- Schrag, J. D., and M. Cygler. 1997. Lipases and alpha/beta hydrolase fold. ''Methods Enzymol'' 284:85-107.
- Spiegel, S., D. Foster, and R. Kolesnick. 1996. Signal transduction through lipid second messengers. ''Curr Opin Cell Biol'' 8:159-67.
- Svendsen, A. 2000. Lipase protein engineering. ''Biochim Biophys Acta'' 1543:223-238.
- Tjoelker, L. W., C. Eberhardt, J. Unger, H. L. Trong, G. A. Zimmerman, T. M. McIntyre, D. M. Stafforini, S. M. Prescott, and P. W. Gray. 1995. Plasma platelet-activating factor acetylhydrolase is a secreted phospholipase A2 with a catalytic triad. ''J Biol Chem'' 270:25481-7.
- Winkler, F. K., A. D'Arcy, and W. Hunziker. 1990. Structure of human pancreatic lipase. ''Nature'' 343:771-4.
- Withers-Martinez, C., F. Carriere, R. Verger, D. Bourgeois, and C. Cambillau. 1996. A pancreatic lipase with a phospholipase A1 activity: crystal structure of a chimeric pancreatic lipase-related protein 2 from guinea pig. ''Structure'' 4:1363-74.
|
