Intestinal bile acids (which aid lipid digestion by facilitatingmicelle 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 CLPSgene.[6]
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 conserveddisulphide 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]
Protein domain
Colipase N-terminal domain
Structure of the pancreatic lipase-colipase complex inhibited by a C11 alkyl phosphonate.[9]
^"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, Bruce M.; Stanton, Bruce A.; Swiatecka-Urban, Agnieszka, eds. (2024).Berne & Levy Physiology (8th ed.). Philadelphia, PA: Elsevier.ISBN978-0-323-84790-2.
^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):262–5.doi:10.1016/0888-7543(91)90509-D.PMID2045105.
^abVerger R, van Tilbeurgh H, Cambillau C, Bezzine S, Carriere F (1999). "Colipase: structure and interaction with pancreatic lipase".Biochim. Biophys. Acta.1441 (2–3):173–184.doi:10.1016/s1388-1981(99)00149-3.PMID10570245.
^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):2751–62.doi:10.1021/bi00009a003.PMID7893686.
Miled N, Canaan S, Dupuis L, et al. (2000). "Digestive lipases: from three-dimensional structure to physiology".Biochimie.82 (11):973–86.doi:10.1016/S0300-9084(00)01179-2.PMID11099794.
Lindner I, Helwig U, Rubin D, et al. (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".Mol Nutr Food Res.49 (10):972–6.doi:10.1002/mnfr.200500087.PMID16189801.
Sims HF, Lowe ME (1992). "The human colipase gene: isolation, chromosomal location, and tissue-specific expression".Biochemistry.31 (31):7120–5.doi:10.1021/bi00146a013.PMID1643046.
Lowe ME, Rosenblum JL, McEwen P, Strauss AW (1990). "Cloning and characterization of the human colipase cDNA".Biochemistry.29 (3):823–8.doi:10.1021/bi00455a032.PMID2337598.
van Tilbeurgh H, Bezzine S, Cambillau C, et al. (1999). "Colipase: structure and interaction with pancreatic lipase".Biochim. Biophys. Acta.1441 (2–3):173–84.doi:10.1016/s1388-1981(99)00149-3.PMID10570245.
Sternby B, Engström A, Hellman U, et al. (1984). "The primary sequence of human pancreatic colipase".Biochim. Biophys. Acta.784 (1):75–80.doi:10.1016/0167-4838(84)90175-4.PMID6691986.
Sias B, Ferrato F, Grandval P, et al. (2004). "Human pancreatic lipase-related protein 2 is a galactolipase".Biochemistry.43 (31):10138–48.doi:10.1021/bi049818d.PMID15287741.
Sugar IP, Mizuno NK, Momsen MM, et al. (2003). "Regulation of lipases by lipid-lipid interactions: implications for lipid-mediated signaling in cells".Chem. Phys. Lipids.122 (1–2):53–64.doi:10.1016/S0009-3084(02)00178-0.PMID12598038.
Davis RC, Xia YR, Mohandas T, et al. (1991). "Assignment of the human pancreatic colipase gene to chromosome 6p21.1 to pter".Genomics.10 (1):262–5.doi:10.1016/0888-7543(91)90509-D.PMID2045105.
