Colipase Explained

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.^[1]

In humans, the colipase protein is encoded by the CLPS gene.^[2]

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.^{[3] [4]}

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.^[4]

Symbol: Colipase Colipase N-terminal domain Pfam: PF01114 Interpro: IPR001981 Prosite: PDOC00111 Scop: 1lpb Cdd: cd00039 Pdb: ,,,,,

Symbol:	Colipase_C
Colipase C-terminal domain
Pfam:	PF02740
Interpro:	IPR017914
Prosite:	PDOC00111
Scop:	1lpb
Cdd:	cd00039

See also

• Enterostatin

Further reading

• Weyrich P, Albet S, Lammers R . Genetic variability of procolipase associates with altered insulin secretion in non-diabetic Caucasians . Exp. Clin. Endocrinol. Diabetes . 117 . 2 . 83–7 . 2009 . 18726866 . 10.1055/s-2008-1078733 . 260136576 . etal.
• Crandall WV, Lowe ME . Colipase residues Glu64 and Arg65 are essential for normal lipase-mediated fat digestion in the presence of bile salt micelles . J. Biol. Chem. . 276 . 16 . 12505–12 . 2001 . 11278590 . 10.1074/jbc.M009986200 . free .
• Miled N, Canaan S, Dupuis L . Digestive lipases: from three-dimensional structure to physiology . Biochimie . 82 . 11 . 973–86 . 2000 . 11099794 . 10.1016/S0300-9084(00)01179-2 . etal.
• van Tilbeurgh H, Egloff MP, Martinez C . Interfacial activation of the lipase-procolipase complex by mixed micelles revealed by X-ray crystallography . Nature . 362 . 6423 . 814–20 . 1993 . 8479519 . 10.1038/362814a0 . 1993Natur.362..814V . 4305832 . etal.
• Wermter AK, Scherag A, Holter K . Procolipase gene: no association with early-onset obesity or fat intake . Obes Facts . 2 . 1 . 40–4 . 2009 . 20054203 . 6444705 . 10.1159/000196379 . etal.
• Lindner I, Helwig U, Rubin D . 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 . Mol Nutr Food Res . 49 . 10 . 972–6 . 2005 . 16189801 . 10.1002/mnfr.200500087 . etal.
• Sims HF, Lowe ME . The human colipase gene: isolation, chromosomal location, and tissue-specific expression . Biochemistry . 31 . 31 . 7120–5 . 1992 . 1643046 . 10.1021/bi00146a013 .
• Lowe ME, Rosenblum JL, McEwen P, Strauss AW . Cloning and characterization of the human colipase cDNA . Biochemistry . 29 . 3 . 823–8 . 1990 . 2337598 . 10.1021/bi00455a032 .
• van Tilbeurgh H, Bezzine S, Cambillau C . Colipase: structure and interaction with pancreatic lipase . Biochim. Biophys. Acta . 1441 . 2–3 . 173–84 . 1999 . 10570245 . 10.1016/s1388-1981(99)00149-3. etal.
• D'Silva S, Xiao X, Lowe ME . A polymorphism in the gene encoding procolipase produces a colipase, Arg92Cys, with decreased function against long-chain triglycerides . J. Lipid Res. . 48 . 11 . 2478–84 . 2007 . 17715423 . 10.1194/jlr.M700371-JLR200 . free . 3684974 .
• Gerhard DS, Wagner L, Feingold EA . The Status, Quality, and Expansion of the NIH Full-Length cDNA Project: The Mammalian Gene Collection (MGC) . Genome Res. . 14 . 10B . 2121–7 . 2004 . 15489334 . 528928 . 10.1101/gr.2596504 . etal.
• Sternby B, Engström A, Hellman U . The primary sequence of human pancreatic colipase . Biochim. Biophys. Acta . 784 . 1 . 75–80 . 1984 . 6691986 . 10.1016/0167-4838(84)90175-4 . etal.
• Sias B, Ferrato F, Grandval P . Human pancreatic lipase-related protein 2 is a galactolipase . Biochemistry . 43 . 31 . 10138–48 . 2004 . 15287741 . 10.1021/bi049818d . etal.
• Lowe ME . Structure and function of pancreatic lipase and colipase . Annu. Rev. Nutr. . 17 . 141–58 . 1997 . 9240923 . 10.1146/annurev.nutr.17.1.141 .
• Strausberg RL, Feingold EA, Grouse LH . Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences . Proc. Natl. Acad. Sci. U.S.A. . 99 . 26 . 16899–903 . 2002 . 12477932 . 139241 . 10.1073/pnas.242603899 . 2002PNAS...9916899M . etal. free .
• Sugar IP, Mizuno NK, Momsen MM . Regulation of lipases by lipid-lipid interactions: implications for lipid-mediated signaling in cells . Chem. Phys. Lipids . 122 . 1–2 . 53–64 . 2003 . 12598038 . 10.1016/S0009-3084(02)00178-0 . etal.
• van Tilbeurgh H, Sarda L, Verger R, Cambillau C . Structure of the pancreatic lipase-procolipase complex . Nature . 359 . 6391 . 159–62 . 1992 . 1522902 . 10.1038/359159a0 . 1992Natur.359..159V . 4360354 .
• Davis RC, Xia YR, Mohandas T . Assignment of the human pancreatic colipase gene to chromosome 6p21.1 to pter . Genomics . 10 . 1 . 262–5 . 1991 . 2045105 . 10.1016/0888-7543(91)90509-D . etal.

External links

• • PDBe-KB provides an overview of all the structure information available in the PDB for Pig Colipase

Notes and References

1. Book: Berne & Levy Physiology . Elsevier . 2024 . 978-0-323-84790-2 . Koeppen . Bruce M. . 8th . Philadelphia, PA . Stanton . Bruce A. . Swiatecka-Urban . Agnieszka.
2. Davis RC, Xia YR, Mohandas T, Schotz MC, Lusis AJ . Assignment of the human pancreatic colipase gene to chromosome 6p21.1 to pter . Genomics . 10 . 1 . 262–5 . May 1991 . 2045105 . 10.1016/0888-7543(91)90509-D.
3. 10.1146/annurev.nutr.17.1.141 . Lowe ME . Structure and function of pancreatic lipase and colipase . Annu. Rev. Nutr. . 17 . 141–158 . 1997 . 9240923.
4. Verger R, van Tilbeurgh H, Cambillau C, Bezzine S, Carriere F . Colipase: structure and interaction with pancreatic lipase . Biochim. Biophys. Acta . 1441 . 2–3 . 173–184 . 1999 . 10570245 . 10.1016/s1388-1981(99)00149-3.