The lipase C-terminal domain. A novel unusual inhibitor of pancreatic lipase activity.
Identifieur interne : 000209 ( PubMed/Checkpoint ); précédent : 000208; suivant : 000210The lipase C-terminal domain. A novel unusual inhibitor of pancreatic lipase activity.
Auteurs : L. Ayvazian [France] ; B. Kerfelec ; S. Granon ; E. Foglizzo ; I. Crenon ; C. Dubois ; C. ChapusSource :
- The Journal of biological chemistry [ 0021-9258 ] ; 2001.
English descriptors
- KwdEn :
- Animals, Binding Sites, Chromatography, Gel, Colipases (chemistry), Colipases (isolation & purification), Enzyme Inhibitors (pharmacology), Kinetics, Lipase (chemistry), Lipase (isolation & purification), Male, Micelles, Models, Molecular, Pancreas (enzymology), Protein Binding, Protein Conformation, Protein Structure, Tertiary, Rats, Rats, Wistar, Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization.
- MESH :
- chemical , chemistry : Colipases, Lipase.
- chemical , isolation & purification : Colipases, Lipase.
- chemical , pharmacology : Enzyme Inhibitors.
- enzymology : Pancreas.
- Animals, Binding Sites, Chromatography, Gel, Kinetics, Male, Micelles, Models, Molecular, Protein Binding, Protein Conformation, Protein Structure, Tertiary, Rats, Rats, Wistar, Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization.
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.
DOI: 10.1074/jbc.M010328200
PubMed: 11154696
Affiliations:
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pubmed:11154696Le document en format XML
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<term>Colipases (isolation & purification)</term>
<term>Enzyme Inhibitors (pharmacology)</term>
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<term>Lipase (chemistry)</term>
<term>Lipase (isolation & purification)</term>
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<term>Pancreas (enzymology)</term>
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<front><div type="abstract" xml:lang="en">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.</div>
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