TY - JOUR
T1 - Inhibition of lipases by ε-polylysine
AU - Tsujita, Takahiro
AU - Sumiyoshi, Maho
AU - Takaku, Takeshi
AU - Momsen, William E.
AU - Lowe, Mark E.
AU - Brockman, Howard L.
PY - 2003/12
Y1 - 2003/12
N2 - Oral administration of ε-polylysine to rats reduced the peak plasma triacylglycerol concentration. In vitro, ε-polylysine and polylysine strongly inhibited the hydrolysis, by either pancreatic lipase or carboxylester lipase, of trioleoylglycerol (TO) emulsified with phosphatidylcholine (PC) and taurocholate. The ε-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, ε-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, ε-polylysine becomes surface active and adsorbs to TO-PC monomolecular films. These results are consistent with ε-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.
AB - Oral administration of ε-polylysine to rats reduced the peak plasma triacylglycerol concentration. In vitro, ε-polylysine and polylysine strongly inhibited the hydrolysis, by either pancreatic lipase or carboxylester lipase, of trioleoylglycerol (TO) emulsified with phosphatidylcholine (PC) and taurocholate. The ε-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, ε-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, ε-polylysine becomes surface active and adsorbs to TO-PC monomolecular films. These results are consistent with ε-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.
KW - Basic peptide
KW - Complex
KW - Lipid emulsion
KW - Lipid monolayer
UR - http://www.scopus.com/inward/record.url?scp=0347753240&partnerID=8YFLogxK
U2 - 10.1194/jlr.M300151-JLR200
DO - 10.1194/jlr.M300151-JLR200
M3 - Article
C2 - 12951365
AN - SCOPUS:0347753240
VL - 44
SP - 2278
EP - 2286
JO - Journal of Lipid Research
JF - Journal of Lipid Research
SN - 0022-2275
IS - 12
ER -