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Effects of Surfactants on Lipase Structure, Activity, and Inhibition

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ABSTRACT

Lipase inhibitors are the main anti-obesity drugs prescribed these days, but the complexity of their mechanism of action is making it difficult to develop new molecules for this purpose. The efficacy of these drugs is known to depend closely on the physico-chemistry of the lipid-water interfaces involved and on the unconventional behavior of the lipases which are their target enzymes. The lipolysis reaction which occurs at an oil-water interface involves complex equilibria between adsorption-desorption processes, conformational changes and catalytic mechanisms. In this context, surfactants can induce significant changes in the partitioning of the enzyme and the inhibitor between the water phase and lipid-water interfaces. Surfactants can be found at the oil-water interface where they compete with lipases for adsorption, but also in solution in the form of micellar aggregates and monomers that may interact with hydrophobic parts of lipases in solution. These various interactions, combined with the emulsification and dispersion of insoluble substrates and inhibitors, can either promote or decrease the activity and the inhibition of lipases. Here, we review some examples of the various effects of surfactants on lipase structure, activity and inhibition, which show how complex the various equilibria involved in the lipolysis reaction tend to be.

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Abbreviations

β-OG:

β-octyl glucoside

BSA:

bovine serum albumin

CMC:

critical micellar concentration

DGL:

dog gastric lipase

EPR:

electron paramagnetic resonance

E600:

diethyl p-nitrophenyl phosphate

GPLRP2:

guinea pig pancreatic lipase-related protein 2

HPL:

human pancreatic lipase

NaTDC:

sodium taurodeoxycholate

PPL:

porcine pancreatic lipase

SDS:

sodium dodecyl sulphate

SDSL:

site-directed spin labeling

TAG:

triacylglycerol

TGME:

tetraethylene glycol monooctyl ether

THL:

tetrahydrolipstatin (Orlistat)

TLL:

Thermomyces lanuginosus lipase

YLLip2:

Yarrowia lipolytica Lip2

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ACKNOWLEDGMENTS

V. Delorme was financed by a PhD fellowship from the Ministère de l’Enseignement Supérieur et de la Recherche. This work was supported by the CNRS and by the Agence Nationale de la Recherche Française (ANR PCV 2007–184840 PHELIN, ANR MIEN 2009–00904 FOAMY_TUB). Authors would like to thank Dr. J. Blanc for revising the English.

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  1. CNRS - Aix-Marseille Université - Enzymologie Interfaciale et Physiologie de la Lipolyse, UPR 9025, 31 chemin Joseph Aiguier, 13402, Marseille cedex 20, France

    Vincent Delorme, Rabeb Dhouib, Stéphane Canaan, Frédéric Carrière & Jean-François Cavalier

  2. UMR 6263 CNRS-École Centrale Marseille-Université Paul Cézanne, Equipe Chirosciences, Avenue Escadrille Normandie-Niemen, 13397, Marseille Cedex 20, France

    Vincent Delorme & Frédéric Fotiadu

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  1. Vincent Delorme
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Correspondence to Frédéric Carrière or Jean-François Cavalier.

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Delorme, V., Dhouib, R., Canaan, S. et al. Effects of Surfactants on Lipase Structure, Activity, and Inhibition. Pharm Res 28, 1831–1842 (2011). https://doi.org/10.1007/s11095-010-0362-9

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  • DOI: https://doi.org/10.1007/s11095-010-0362-9

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