Lipaza

Lipaza je enzim koji katalizuje formiranje ili raskidanje (hidrolizu) masti (lipida).^[1] Lipaze u potklasa esteraza.

Lipaze imaju esencijalne uloge u varenju, transportu i preradi dijetarnih lipida (e.g. triglicerida, masti, ulja) u većini, ako ne i u svim, živim organizmima. Geni koji kodiraju lipaze su čak prisutni i u pojedinim virusima.^[2]^[3]

Funkcija

Većina lipaza deluje na specifičnoj poziciji na glicerolnoj osnovi lipidnog supstrata (A₁, A₂ ili A₃) (tanka creva). Na primer, lipaza ljudskog pankreasa (HPL),^[4] koja je glavni enzim za razlaganje dijetarne masti u ljudskom digestivnom sistemu, konvertuje trigliceridne supstrate ulja u monogliceride i masne kiseline.

Nekoliko drugih tipova lipaza se javlja u prirodi, poput fosfolipaza^[5] i sfingomijelinaza,^[6] međutim one se obično razmatraju zasebno od "konvencionih" lipaza.

Neke lipaze izražavaju i izlučuju patogeni organizmi tokom infekcije. Candida albicans ima posebno veliki broj različitih lipaza, sa širokim spektrom lipidnog dejstva. To doprinosi istrajnosti i virulenciji C. albicans u ljudskom tkivu.^[7]

Struktura i katalitički mehanizam

Raznovrstan niz genetički jedinstvenih lipaza je nađen u prirodi. One predstavljaju nekoliko tipova savijanja proteina i katalitičkih mehanizama. Većina lipaza ima strukturu alfa/beta hidrolaznog savijanja^[4]^[8]^[9]^[10] i koristi hidrolazni mehanizam sličan mehanizmu himotripsina u kome učestvuje serinski nukleofil, kiseli ostatak (obično aspartična kiselina), i histidin.^[11]^[12]

Reference

↑ Svendsen A (2000). „Lipase protein engineering”. Biochim Biophys Acta 1543 (2): 223–228. DOI:10.1016/S0167-4838(00)00239-9. PMID 11150608.
↑ Afonso C, Tulman E, Lu Z, Oma E, Kutish G, Rock D (1999). „The Genome of Melanoplus sanguinipes Entomopoxvirus”. J Virol 73 (1): 533–52. PMC 103860. PMID 9847359.
↑ Girod A, Wobus C, Zádori Z, Ried M, Leike K, Tijssen P, Kleinschmidt J, Hallek M (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 (Pt 5): 973–8. PMID 11961250.
↑ ^4,0 ^4,1 Winkler FK, D'Arcy A, and W Hunziker (1990). „Structure of human pancreatic lipase”. Nature 343 (6260): 771–774. DOI:10.1038/343771a0. PMID 2106079.
↑ Diaz, B.L., and J. P. Arm. (2003). „Phospholipase A(2)”. Prostaglandins Leukot Essent Fatty Acids 2-3 (2–3): 87–97. DOI:10.1016/S0952-3278(03)00069-3. PMID 12895591.
↑ Goñi F, Alonso A (2002). „Sphingomyelinases: enzymology and membrane activity”. FEBS Lett 531 (1): 38–46. DOI:10.1016/S0014-5793(02)03482-8. PMID 12401200.
↑ Hube B, Stehr F, Bossenz M, Mazur A, Kretschmar M, Schafer W (2000). „Secreted lipases of Candida albicans: cloning, characterisation and expression analysis of a new gene family with at least ten members”. Arch. Microbiol. 174 (5): 362–374. DOI:10.1007/s002030000218. PMID 11131027.
↑ Schrag J, Cygler M (1997). „Lipases and alpha/beta hydrolase fold”. Methods Enzymol. Methods in Enzymology 284: 85–107. DOI:10.1016/S0076-6879(97)84006-2. ISBN 9780121821852. PMID 9379946.
↑ Egmond, M. R., and C. J. van Bemmel (1997). „Impact of Structural Information on Understanding of Lipolytic Function”. Methods Enzymol. Methods in Enzymology 284: 119–129. DOI:10.1016/S0076-6879(97)84008-6. ISBN 9780121821852. PMID 9379930.
↑ Withers-Martinez C, Carriere F, Verger R, Bourgeois D, 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 (11): 1363–74. DOI:10.1016/S0969-2126(96)00143-8. PMID 8939760.
↑ 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 (6260): 767–70. DOI:10.1038/343767a0. PMID 2304552.
↑ Lowe ME (1992). „The catalytic site residues and interfacial binding of human pancreatic lipase”. J Biol Chem 267 (24): 17069–73. PMID 1512245.

Literatura

Nicholas C. Price, Lewis Stevens (1999). Fundamentals of Enzymology: The Cell and Molecular Biology of Catalytic Proteins (Third izd.). USA: Oxford University Press. ISBN 019850229X.
Eric J. Toone (2006). Advances in Enzymology and Related Areas of Molecular Biology, Protein Evolution (Volume 75 izd.). Wiley-Interscience. ISBN 0471205036.
Branden C, Tooze J.. Introduction to Protein Structure. New York, NY: Garland Publishing. ISBN: 0-8153-2305-0.
Irwin H. Segel. Enzyme Kinetics: Behavior and Analysis of Rapid Equilibrium and Steady-State Enzyme Systems (Book 44 izd.). Wiley Classics Library. ISBN 0471303097.
Robert A. Copeland (2013). Evaluation of Enzyme Inhibitors in Drug Discovery: A Guide for Medicinal Chemists and Pharmacologists (2nd izd.). Wiley-Interscience. ISBN 111848813X.
Gerhard Michal, Dietmar Schomburg (2012). Biochemical Pathways: An Atlas of Biochemistry and Molecular Biology (2nd izd.). Wiley. ISBN 0470146842.

Povezano

Vanjske veze

MeSH Lipase
Selektivni inhibitori monoacilglicerolne lipaze kao tretman za neurološke poremećaje Arhivirano 2012-02-20 na Wayback Machine-u
UMich orijentacija proteina u membranama families/superfamily-90 - Fosfolipaze A2
UMich orijentacija proteina u membranama families/superfamily-29 - Druga membranska fosfolipaza A
UMich orijentacija proteina u membranama families/superfamily-134 - Citosolna fosfolipaza A2 i patatin
UMich orijentacija proteina u membranama families/superfamily-126 - Bakterijska i sisarske fosfolipaze C
UMich orijentacija proteina u membranama families/superfamily-88 - α-toksin (bakterijska fosfolipaza C)

[1] Svendsen A (2000). „Lipase protein engineering”. Biochim Biophys Acta 1543 (2): 223–228. DOI:10.1016/S0167-4838(00)00239-9. PMID 11150608.

[2] Afonso C, Tulman E, Lu Z, Oma E, Kutish G, Rock D (1999). „The Genome of Melanoplus sanguinipes Entomopoxvirus”. J Virol 73 (1): 533–52. PMC 103860. PMID 9847359.

[3] Girod A, Wobus C, Zádori Z, Ried M, Leike K, Tijssen P, Kleinschmidt J, Hallek M (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 (Pt 5): 973–8. PMID 11961250.

[Winkler_FK,_D'Arcy_A,_and_W_Hunziker_1990_771–774-4] 4,0 ^4,1 Winkler FK, D'Arcy A, and W Hunziker (1990). „Structure of human pancreatic lipase”. Nature 343 (6260): 771–774. DOI:10.1038/343771a0. PMID 2106079.

[5] Diaz, B.L., and J. P. Arm. (2003). „Phospholipase A(2)”. Prostaglandins Leukot Essent Fatty Acids 2-3 (2–3): 87–97. DOI:10.1016/S0952-3278(03)00069-3. PMID 12895591.

[6] Goñi F, Alonso A (2002). „Sphingomyelinases: enzymology and membrane activity”. FEBS Lett 531 (1): 38–46. DOI:10.1016/S0014-5793(02)03482-8. PMID 12401200.

[PUB00008352-7] Hube B, Stehr F, Bossenz M, Mazur A, Kretschmar M, Schafer W (2000). „Secreted lipases of Candida albicans: cloning, characterisation and expression analysis of a new gene family with at least ten members”. Arch. Microbiol. 174 (5): 362–374. DOI:10.1007/s002030000218. PMID 11131027.

[8] Schrag J, Cygler M (1997). „Lipases and alpha/beta hydrolase fold”. Methods Enzymol. Methods in Enzymology 284: 85–107. DOI:10.1016/S0076-6879(97)84006-2. ISBN 9780121821852. PMID 9379946.

[9] Egmond, M. R., and C. J. van Bemmel (1997). „Impact of Structural Information on Understanding of Lipolytic Function”. Methods Enzymol. Methods in Enzymology 284: 119–129. DOI:10.1016/S0076-6879(97)84008-6. ISBN 9780121821852. PMID 9379930.

[10] Withers-Martinez C, Carriere F, Verger R, Bourgeois D, 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 (11): 1363–74. DOI:10.1016/S0969-2126(96)00143-8. PMID 8939760.

[11] 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 (6260): 767–70. DOI:10.1038/343767a0. PMID 2304552.

[12] Lowe ME (1992). „The catalytic site residues and interfacial binding of human pancreatic lipase”. J Biol Chem 267 (24): 17069–73. PMID 1512245.

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