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.[6]
In humans, the colipase protein is encoded by the CLPS gene.[7]
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.[8][9]
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.[9]
More information Identifiers, Symbol ...
Colipase N-terminal domain
Structure of the pancreatic lipase-colipase complex inhibited by a C11 alkyl phosphonate.[10]
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. PMID2045105.
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. PMID7893686.
Further reading
Weyrich P, Albet S, Lammers R, Machicao F, Fritsche A, Stefan N, etal. (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. PMID18726866. S2CID260136576.
Miled N, Canaan S, Dupuis L, Roussel A, Rivière M, Carrière F, etal. (November 2000). "Digestive lipases: from three-dimensional structure to physiology". Biochimie. 82 (11): 973–986. doi:10.1016/S0300-9084(00)01179-2. PMID11099794.
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. PMID8479519. S2CID4305832.
Lindner I, Helwig U, Rubin D, Li Y, Fisher E, Boeing H, etal. (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. PMID16189801.
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. PMID1643046.
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. PMID2337598.
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. PMID6691986.
Sias B, Ferrato F, Grandval P, Lafont D, Boullanger P, De Caro A, etal. (August 2004). "Human pancreatic lipase-related protein 2 is a galactolipase". Biochemistry. 43 (31): 10138–10148. doi:10.1021/bi049818d. PMID15287741.
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. PMID12598038.
