title: The lipase C-terminal domain. A novel unusual inhibitor of pancreatic lipase activity.
abstract: In vertebrates, dietary fat digestion mainly results from the combined effect of pancreatic lipase, colipase, and bile. It has been proposed that in vivo lipase adsorption on oil-water emulsion is mediated by a preformed lipase-colipase-mixed micelle complex. The main lipase-colipase binding site is located on the C-terminal domain of the enzyme. We report here that in vitro the isolated C-terminal domain behaves as a potent noncovalent inhibitor of lipase and that the inhibitory effect is triggered by the presence of micelles. Lipase inhibition results from the formation of a nonproductive C-terminal domain-colipase-micelle ternary complex, which competes for colipase with the active lipase-colipase-micelle ternary complex, thus diverting colipase from its lipase-anchoring function. The formation of such a complex has been evidenced by molecular sieving experiments. This nonproductive complex lowers the amount of active lipase thus reducing lipolysis. Preliminary experiments performed in rats show that the C-terminal domain also behaves as an inhibitor in vivo and thus could be considered a potential new tool for specifically reducing intestinal lipolysis.
authors.affiliation: INSERM -U476 Nutrition Humaine et Lipides, 18 Avenue Mozart 13009 Marseille, France.
authors.forename: L
authors.initials: L
authors.lastname: Ayvazian
authors.forename: B
authors.initials: B
authors.lastname: Kerfelec
authors.forename: S
authors.initials: S
authors.lastname: Granon
authors.forename: E
authors.initials: E
authors.lastname: Foglizzo
authors.forename: I
authors.initials: I
authors.lastname: Crenon
authors.forename: C
authors.initials: C
authors.lastname: Dubois
authors.forename: C
authors.initials: C
authors.lastname: Chapus
mesh_terms: D000818:Animals; D001665:Binding Sites; D002850:Chromatography, Gel; D003089:Colipases / Q000737:chemistry / Q000302:isolation & purification; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D007700:Kinetics; D008049:Lipase / Q000737:chemistry* / Q000302:isolation & purification; D008297:Male; D008823:Micelles; D008958:Models, Molecular; D010179:Pancreas / Q000201:enzymology*; D011485:Protein Binding; D011487:Protein Conformation; D017434:Protein Structure, Tertiary; D051381:Rats; D017208:Rats, Wistar; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
chemical_list: D003089:Colipases; D004791:Enzyme Inhibitors; D008823:Micelles; D008049:Lipase