Lipaza

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

Prikaz pankreasne lipaze (PLRP2) morkog praseta. PDB: 1GPL.

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. PMID 11150608. doi:10.1016/S0167-4838(00)00239-9.
^ 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.
^ ^а ^б Winkler FK; D'Arcy A & W Hunziker (1990). „Structure of human pancreatic lipase”. Nature. 343 (6260): 771—774. PMID 2106079. doi:10.1038/343771a0.
^ Diaz, B.L. & J. P. Arm. (2003). „Phospholipase A(2)”. Prostaglandins Leukot Essent Fatty Acids. 2—3 (2–3): 87—97. PMID 12895591. doi:10.1016/S0952-3278(03)00069-3.
^ Goñi F, Alonso A (2002). „Sphingomyelinases: enzymology and membrane activity”. FEBS Lett. 531 (1): 38—46. PMID 12401200. doi:10.1016/S0014-5793(02)03482-8.
^ 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. PMID 11131027. doi:10.1007/s002030000218.
^ Schrag J, Cygler M (1997). „Lipases and alpha/beta hydrolase fold”. Methods Enzymol. Methods in Enzymology. 284: 85—107. ISBN 9780121821852. PMID 9379946. doi:10.1016/S0076-6879(97)84006-2.
^ Egmond, M. R. & C. J. van Bemmel (1997). „Impact of Structural Information on Understanding of Lipolytic Function”. Methods Enzymol. Methods in Enzymology. 284: 119—129. ISBN 9780121821852. PMID 9379930. doi:10.1016/S0076-6879(97)84008-6.
^ Withers-Martinez C; Carriere F; Verger R; Bourgeois D & 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. PMID 8939760. doi:10.1016/S0969-2126(96)00143-8.
^ 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. PMID 2304552. doi:10.1038/343767a0.
^ 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 изд.). USA: Oxford University Press. ISBN 019850229X.
Eric J. Toone (2006). Advances in Enzymology and Related Areas of Molecular Biology, Protein Evolution (Volume 75 изд.). 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 изд.). Wiley Classics Library. ISBN 0471303097.

Vidi još

Spoljašnje veze

Lipase на US National Library of Medicine Medical Subject Headings (MeSH)
Selektivni inhibitori monoacilglicerolne lipaze kao tretman za neurološke poremećaje
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. PMID 11150608. doi:10.1016/S0167-4838(00)00239-9.

[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] а ^б Winkler FK; D'Arcy A & W Hunziker (1990). „Structure of human pancreatic lipase”. Nature. 343 (6260): 771—774. PMID 2106079. doi:10.1038/343771a0.

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

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

[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. PMID 11131027. doi:10.1007/s002030000218.

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

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

[10] Withers-Martinez C; Carriere F; Verger R; Bourgeois D & 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. PMID 8939760. doi:10.1016/S0969-2126(96)00143-8.

[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. PMID 2304552. doi:10.1038/343767a0.

[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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