Kolipase
| CLPS | |||||||||||||||||||||||||||||||||||||||||||||||||||
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| Pengidentifikasi | |||||||||||||||||||||||||||||||||||||||||||||||||||
| Alias | CLPS, entrez:1208, colipase | ||||||||||||||||||||||||||||||||||||||||||||||||||
| ID Eksternal | OMIM: 120105; MGI: 88421; HomoloGene: 1383; GeneCards: CLPS; OMA:CLPS - orthologs | ||||||||||||||||||||||||||||||||||||||||||||||||||
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Kolipase, disingkat CLPS, adalah protein koenzim yang menangkal efek penghambatan asam empedu usus terhadap aktivitas enzimatik lipase pankreas. Protein ini disekresikan oleh pankreas dalam bentuk tidak aktif, yaitu prokolipase, yang kemudian diaktifkan di dalam lumen usus oleh tripsin.
Asam empedu usus (yang membantu pencernaan lipid dengan memfasilitasi pembentukan misel) melekat pada permukaan tetesan lemak teremulsi, sehingga menggeser lipase (yang hanya aktif pada antarmuka air-lemak) dari permukaan tetesan tersebut. Kolipase bertindak sebagai molekul penjembatan, yang berikatan dengan lipase dan asam empedu, sehingga menambatkan lipase ke permukaan tetesan dan mencegah pergeserannya.[3]
Pada manusia, protein kolipase dikodekan oleh gen CLPS.[4]
Domain protein
Kolipase juga merupakan famili protein yang berkerabat secara evolusioner.
Kolipase adalah kofaktor protein kecil yang dibutuhkan oleh lipase pankreas untuk hidrolisis lipid makanan yang efisien. Penyerapan lemak makanan yang efisien bergantung pada kerja lipase trigliserida pankreas. Kolipase berikatan dengan domain terminal-C lipase yang bersifat non-katalitik, sehingga menstabilkan konformasi aktif dan meningkatkan hidrofobisitas situs pengikatannya secara signifikan. Studi struktural terhadap kompleks ini dan kolipase saja telah mengungkapkan fungsionalitas arsitekturnya.[5][6]
Kolipase adalah protein kecil (12K) dengan lima ikatan disulfida yang terkonservasi. Analogi struktural telah dikenali antara protein perkembangan (Dickkopf), domain terminal-C lipase pankreas, domain terminal-N lipoksigenase, dan domain terminal-C alfa-toksin. Domain non-katalitik pada enzim-enzim tersebut penting untuk interaksi dengan membran. Belum dipastikan apakah domain ini juga terlibat dalam pengikatan kofaktor protein sebagaimana yang terjadi pada lipase pankreas.[6]
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| Domain terminal-C kolipase | |||||||||
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Struktur larutan prokolipase pankreas babi sebagaimana ditentukan dari NMR homonuklear 1h dua dan tiga dimensi | |||||||||
| Identifikasi | |||||||||
| Simbol | Colipase_C | ||||||||
| Pfam | PF02740 | ||||||||
| InterPro | IPR017914 | ||||||||
| PROSITE | PDOC00111 | ||||||||
| SCOP | 1lpb | ||||||||
| SUPERFAMILY | 1lpb | ||||||||
| CDD | cd00039 | ||||||||
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Lihat pula
Referensi
- ^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
- ^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
- ^ Koeppen BM, Stanton BA, Swiatecka-Urban A, ed. (2024). Berne & Levy Physiology (Edisi 8th). Philadelphia, PA: Elsevier. ISBN 978-0-323-84790-2.
- ^ Davis RC, Xia YR, Mohandas T, Schotz MC, Lusis AJ (May 1991). "Assignment of the human pancreatic colipase gene to chromosome 6p21.1 to pter". Genomics. 10 (1): 262–265. doi:10.1016/0888-7543(91)90509-D. PMID 2045105.
- ^ Lowe ME (1997). "Structure and function of pancreatic lipase and colipase". Annual Review of Nutrition. 17 (1): 141–158. doi:10.1146/annurev.nutr.17.1.141. PMID 9240923.
- ^ a b Verger R, van Tilbeurgh H, Cambillau C, Bezzine S, Carriere F (1999). "Colipase: structure and interaction with pancreatic lipase". Biochimica et Biophysica Acta. 1441 (2–3): 173–184. doi:10.1016/s1388-1981(99)00149-3. PMID 10570245.
- ^ Egloff MP, Marguet F, Buono G, Verger R, Cambillau C, van Tilbeurgh H (March 1995). "The 2.46 A resolution structure of the pancreatic lipase-colipase complex inhibited by a C11 alkyl phosphonate". Biochemistry. 34 (9): 2751–2762. doi:10.1021/bi00009a003. PMID 7893686.
Bacaan lebih lanjut
- Weyrich P, Albet S, Lammers R, Machicao F, Fritsche A, Stefan N, et al. (February 2009). "Genetic variability of procolipase associates with altered insulin secretion in non-diabetic Caucasians". Experimental and Clinical Endocrinology & Diabetes. 117 (2): 83–87. doi:10.1055/s-2008-1078733. PMID 18726866. S2CID 260136576.
- Crandall WV, Lowe ME (2001). "Colipase residues Glu64 and Arg65 are essential for normal lipase-mediated fat digestion in the presence of bile salt micelles". The Journal of Biological Chemistry. 276 (16): 12505–12512. doi:10.1074/jbc.M009986200. PMID 11278590.
- Miled N, Canaan S, Dupuis L, Roussel A, Rivière M, Carrière F, et al. (November 2000). "Digestive lipases: from three-dimensional structure to physiology". Biochimie. 82 (11): 973–986. doi:10.1016/S0300-9084(00)01179-2. PMID 11099794.
- van Tilbeurgh H, Egloff MP, Martinez C, Rugani N, Verger R, Cambillau C (April 1993). "Interfacial activation of the lipase-procolipase complex by mixed micelles revealed by X-ray crystallography". Nature. 362 (6423): 814–820. Bibcode:1993Natur.362..814V. doi:10.1038/362814a0. PMID 8479519. S2CID 4305832.
- Wermter AK, Scherag A, Holter K, Reichwald K, Lichtner P, Siegfried W, et al. (2009). "Procolipase gene: no association with early-onset obesity or fat intake". Obesity Facts. 2 (1): 40–44. doi:10.1159/000196379. PMC 6444705. PMID 20054203.
- Lindner I, Helwig U, Rubin D, Li Y, Fisher E, Boeing H, et al. (October 2005). "Putative association between a new polymorphism in exon 3 (Arg109Cys) of the pancreatic colipase gene and type 2 diabetes mellitus in two independent Caucasian study populations". Molecular Nutrition & Food Research. 49 (10): 972–976. doi:10.1002/mnfr.200500087. PMID 16189801.
- Sims HF, Lowe ME (1992). "The human colipase gene: isolation, chromosomal location, and tissue-specific expression". Biochemistry. 31 (31): 7120–7125. doi:10.1021/bi00146a013. PMID 1643046.
- Lowe ME, Rosenblum JL, McEwen P, Strauss AW (1990). "Cloning and characterization of the human colipase cDNA". Biochemistry. 29 (3): 823–828. doi:10.1021/bi00455a032. PMID 2337598.
- D'Silva S, Xiao X, Lowe ME (2007). "A polymorphism in the gene encoding procolipase produces a colipase, Arg92Cys, with decreased function against long-chain triglycerides". Journal of Lipid Research. 48 (11): 2478–2484. doi:10.1194/jlr.M700371-JLR200. PMC 3684974. PMID 17715423.
- Sternby B, Engström A, Hellman U, Vihert AM, Sternby NH, Borgström B (January 1984). "The primary sequence of human pancreatic colipase". Biochimica et Biophysica Acta. 784 (1): 75–80. doi:10.1016/0167-4838(84)90175-4. PMID 6691986.
- Sias B, Ferrato F, Grandval P, Lafont D, Boullanger P, De Caro A, et al. (August 2004). "Human pancreatic lipase-related protein 2 is a galactolipase". Biochemistry. 43 (31): 10138–10148. doi:10.1021/bi049818d. PMID 15287741.
- Sugar IP, Mizuno NK, Momsen MM, Momsen WE, Brockman HL (January 2003). "Regulation of lipases by lipid-lipid interactions: implications for lipid-mediated signaling in cells". Chemistry and Physics of Lipids. 122 (1–2): 53–64. doi:10.1016/S0009-3084(02)00178-0. PMID 12598038.
- van Tilbeurgh H, Sarda L, Verger R, Cambillau C (1992). "Structure of the pancreatic lipase-procolipase complex". Nature. 359 (6391): 159–162. Bibcode:1992Natur.359..159V. doi:10.1038/359159a0. PMID 1522902. S2CID 4360354.
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