The lipase C-terminal domain - A novel unusual inhibitor of pancreatic lipase activity

In vertebrates, dietary fat digestion mainly results from the combined effe ct of pancreatic lipase, colipase, and bile. It has been proposed that in v ivo lipase adsorption on oil-water emulsion is mediated by a preformed lipa se-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 vit ro the isolated C-terminal domain behaves as a potent noncovalent inhibitor of lipase and that the inhibitory effect is triggered by the presence of m icelles, Lipase inhibition results from the formation of a nonproductive C- terminal domain-colipase-micelle ternary complex, which competes for colipa se with the active lipase-colipase-micelle ternary complex, thus diverting colipase from its lipase-anchoring function. The formation of such a comple x has been evidenced by molecular sieving experiments. This nonproductive c omplex lowers the amount of active lipase thus reducing lipolysis, Prelimin ary experiments performed in rats show that the C-terminal domain also beha ves as an inhibitor in vivo and thus could be considered a potential new to ol for specifically reducing intestinal lipolysis.