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Originally published In Press as doi:10.1194/jlr.M300151-JLR200 on September 1, 2003

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Journal of Lipid Research, Vol. 44, 2278-2286, December 2003
Copyright © 2003 by American Society for Biochemistry and Molecular Biology

Inhibition of lipases by {varepsilon}-polylysine

Takahiro Tsujita1,*, Maho Sumiyoshi*, Takeshi Takaku*, William E. Momsen{dagger}, Mark E. Lowe§,** and Howard L. Brockman{dagger}

* Central Research Laboratory, School of Medicine, Ehime University, Shigenobu, Onsen-gun, Ehime 791-0295, Japan
{dagger} Hormel Institute, University of Minnesota, Austin, MN 55912
§ Department of Pediatrics, Children's Hospital of Pittsburgh, Pittsburgh, PA 15213
** University of Pittsburgh, Pittsburgh, PA 15213

1 To whom correspondence should be addressed. e-mail: tsujita{at}m.ehime-u.ac.jp

Oral administration of {varepsilon}-polylysine to rats reduced the peak plasma triacylglycerol concentration. In vitro, {varepsilon}-polylysine and polylysine strongly inhibited the hydrolysis, by either pancreatic lipase or carboxylester lipase, of trioleoylglycerol (TO) emulsified with phosphatidylcholine (PC) and taurocholate. The {varepsilon}-polylysine concentration required for complete inhibition of pancreatic lipase, 10 µg/ml, is 1,000 times lower than that of BSA required for the same effect. Inhibition requires the presence of bile salt and, unlike inhibition of lipase by other proteins, is not reversed by supramicellar concentrations of bile salt. Inhibition increases with the degree of polylysine polymerization, is independent of lipase concentration, is independent of pH between 5.0 and 9.5, and is accompanied by an inhibition of lipase binding to TO-PC emulsion particles. However, {varepsilon}-polylysine did not inhibit the hydrolysis by pancreatic lipase of TO emulsions prepared using anionic surfactants, TO hydrolysis catalyzed by lingual lipase, or the hydrolysis of a water-soluble substrate. In the presence of taurocholate, {varepsilon}-polylysine becomes surface active and adsorbs to TO-PC monomolecular films.

These results are consistent with {varepsilon}-polylysine and taurocholate forming a surface-active complex that binds to emulsion particles, thereby retarding lipase adsorption and triacylglycerol hydrolysis both in vivo and in vitro.

Abbreviations: PA, phosphatidic acid; PC, phosphatidylcholine; PE, phosphatidylethanolamine; PS, phosphatidylserine; SOPC, 1-stearoyl-2-oleoyl-sn-glycero-3-phosphocholine; TO, trioleoylglycerol

Supplementary key words basic peptide • complex • lipid emulsion • lipid monolayer


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