The lipase C-terminal domain. A novel unusual inhibitor of pancreatic lipase activity.
Identifieur interne : 002438 ( Main/Exploration ); précédent : 002437; suivant : 002439The 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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Le document en format XML
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Chapus</name></author></titleStmt><publicationStmt><idno type="wicri:source">PubMed</idno><date when="2001">2001</date><idno type="RBID">pubmed:11154696</idno><idno type="pmid">11154696</idno><idno type="doi">10.1074/jbc.M010328200</idno><idno type="wicri:Area/PubMed/Corpus">000245</idno><idno type="wicri:Area/PubMed/Curation">000245</idno><idno type="wicri:Area/PubMed/Checkpoint">000209</idno><idno type="wicri:Area/Ncbi/Merge">000034</idno><idno type="wicri:Area/Ncbi/Curation">000034</idno><idno type="wicri:Area/Ncbi/Checkpoint">000034</idno><idno type="wicri:doubleKey">0021-9258:2001:Ayvazian L:the:lipase:c</idno><idno type="wicri:Area/Main/Merge">002487</idno><idno type="wicri:Area/Main/Curation">002438</idno><idno type="wicri:Area/Main/Exploration">002438</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en">The lipase C-terminal domain. A novel unusual inhibitor of pancreatic lipase activity.</title><author><name sortKey="Ayvazian, L" sort="Ayvazian, L" uniqKey="Ayvazian L" first="L" last="Ayvazian">L. Ayvazian</name><affiliation wicri:level="3"><nlm:affiliation>INSERM -U476 Nutrition Humaine et Lipides, 18 Avenue Mozart 13009 Marseille, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>INSERM -U476 Nutrition Humaine et Lipides, 18 Avenue Mozart 13009 Marseille</wicri:regionArea><placeName><region type="region" nuts="2">Provence-Alpes-Côte d'Azur</region><settlement type="city">Marseille</settlement></placeName></affiliation></author><author><name sortKey="Kerfelec, B" sort="Kerfelec, B" uniqKey="Kerfelec B" first="B" last="Kerfelec">B. Kerfelec</name></author><author><name sortKey="Granon, S" sort="Granon, S" uniqKey="Granon S" first="S" last="Granon">S. Granon</name></author><author><name sortKey="Foglizzo, E" sort="Foglizzo, E" uniqKey="Foglizzo E" first="E" last="Foglizzo">E. Foglizzo</name></author><author><name sortKey="Crenon, I" sort="Crenon, I" uniqKey="Crenon I" first="I" last="Crenon">I. Crenon</name></author><author><name sortKey="Dubois, C" sort="Dubois, C" uniqKey="Dubois C" first="C" last="Dubois">C. Dubois</name></author><author><name sortKey="Chapus, C" sort="Chapus, C" uniqKey="Chapus C" first="C" last="Chapus">C. Chapus</name></author></analytic><series><title level="j">The Journal of biological chemistry</title><idno type="ISSN">0021-9258</idno><imprint><date when="2001" type="published">2001</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Animals</term><term>Binding Sites</term><term>Chromatography, Gel</term><term>Colipases (chemistry)</term><term>Colipases (isolation & purification)</term><term>Enzyme Inhibitors (pharmacology)</term><term>Kinetics</term><term>Lipase (chemistry)</term><term>Lipase (isolation & purification)</term><term>Male</term><term>Micelles</term><term>Models, Molecular</term><term>Pancreas (enzymology)</term><term>Protein Binding</term><term>Protein Conformation</term><term>Protein Structure, Tertiary</term><term>Rats</term><term>Rats, Wistar</term><term>Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization</term></keywords><keywords scheme="MESH" type="chemical" qualifier="chemistry" xml:lang="en"><term>Colipases</term><term>Lipase</term></keywords><keywords scheme="MESH" type="chemical" qualifier="isolation & purification" xml:lang="en"><term>Colipases</term><term>Lipase</term></keywords><keywords scheme="MESH" type="chemical" qualifier="pharmacology" xml:lang="en"><term>Enzyme Inhibitors</term></keywords><keywords scheme="MESH" qualifier="enzymology" xml:lang="en"><term>Pancreas</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Animals</term><term>Binding Sites</term><term>Chromatography, Gel</term><term>Kinetics</term><term>Male</term><term>Micelles</term><term>Models, Molecular</term><term>Protein Binding</term><term>Protein Conformation</term><term>Protein Structure, Tertiary</term><term>Rats</term><term>Rats, Wistar</term><term>Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization</term></keywords></textClass></profileDesc></teiHeader><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></front></TEI><affiliations><list><country><li>France</li></country><region><li>Provence-Alpes-Côte d'Azur</li></region><settlement><li>Marseille</li></settlement></list><tree><noCountry><name sortKey="Chapus, C" sort="Chapus, C" uniqKey="Chapus C" first="C" last="Chapus">C. Chapus</name><name sortKey="Crenon, I" sort="Crenon, I" uniqKey="Crenon I" first="I" last="Crenon">I. Crenon</name><name sortKey="Dubois, C" sort="Dubois, C" uniqKey="Dubois C" first="C" last="Dubois">C. Dubois</name><name sortKey="Foglizzo, E" sort="Foglizzo, E" uniqKey="Foglizzo E" first="E" last="Foglizzo">E. Foglizzo</name><name sortKey="Granon, S" sort="Granon, S" uniqKey="Granon S" first="S" last="Granon">S. Granon</name><name sortKey="Kerfelec, B" sort="Kerfelec, B" uniqKey="Kerfelec B" first="B" last="Kerfelec">B. Kerfelec</name></noCountry><country name="France"><region name="Provence-Alpes-Côte d'Azur"><name sortKey="Ayvazian, L" sort="Ayvazian, L" uniqKey="Ayvazian L" first="L" last="Ayvazian">L. Ayvazian</name></region></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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