Colipase, abbreviated CLPS, is a protein co-enzyme that counteracts the inhibitory effect of intestinal bile acid on the enzymatic activity of pancreatic lipase. It is secreted by the pancreas in an inactive form, procolipase, which is activated in the intestinal lumen by trypsin.
Intestinal bile acids (which aid lipid digestion by facilitating micelle formation) adhere to the surface of emulsified fat droplets, displacing lipase (which is only active at the water-fat interface) from the droplet surface. Colipase acts as a bridging molecule, binding to both lipase and bile acids, thus anchoring lipase onto the droplet surface, preventing its displacement.[5]
In humans, the colipase protein is encoded by the CLPS gene.[6]
Protein domain
Colipase is also a family of evolutionarily related proteins.
Colipase is a small protein cofactor needed by pancreatic lipase for efficient dietary lipid hydrolysis. Efficient absorption of dietary fats is dependent on the action of pancreatic triglyceride lipase. Colipase binds to the C-terminal, non-catalytic domain of lipase, thereby stabilising an active conformation and considerably increasing the hydrophobicity of its binding site. Structural studies of the complex and of colipase alone have revealed the functionality of its architecture.[7][8]
Colipase is a small protein (12K) with five conserved disulphide bonds. Structural analogies have been recognised between a developmental protein (Dickkopf), the pancreatic lipase C-terminal domain, the N-terminal domains of lipoxygenases and the C-terminal domain of alpha-toxin. These non-catalytic domains in the latter enzymes are important for interaction with membrane. It has not been established if these domains are also involved in eventual protein cofactor binding as is the case for pancreatic lipase.[8]
References
- GRCh38: Ensembl release 89: ENSG00000137392 – Ensembl, May 2017
- GRCm38: Ensembl release 89: ENSMUSG00000024225 – Ensembl, May 2017
- "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, eds. (2024). Berne & Levy Physiology (8th ed.). 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.
- 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.
Further reading
- 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.
