Inhibitors of neutral cholesteryl ester hydrolase

E. H. Harrison, D. W. Bernard, P. Scholm, D. M. Quinn, G. H. Rothblat, J. M. Glick

Research output: Contribution to journalArticle

28 Scopus citations

Abstract

p-Nitrophenyl N-butyl, N-octyl, and N-dodecyl carbamates and a newly synthesized diethyl phosphate compound were studied as potential inhibitors of the cholesteryl ester hydrolases of Fu5AH rat hepatoma cells. Whole homogenates of Fu5AH cells were used as an enzyme source for the assay of cholesteryl ester hydrolase activity. All four compounds led to marked inhibition (70-80%) of neutral cholesteryl ester hydrolase activity (assayed at pH 7) at concentrations where the activity of acid cholesteryl ester hydrolase (assayed at pH 4) was unaffected. Cholesteryl ester hydrolysis was also evaluated in intact cultured cells induced to accumulate cholesteryl esters in cytoplasmic lipid droplets by exposure to cholesterol-rich phospholipid dispersions. Hydrolysis was then assessed during subsequent incubations in the presence of an inhibitor of cholesterol esterification. All compounds caused significant inhibition of cholesterol ester hydrolysis with the diethyl phosphate being the most effective. At a concentration that caused >90% inhibition of the hydrolysis of cytoplasmic cholesteryl esters, the compound had only a minimal effect on lysosomal hydrolysis of cholesteryl esters. These results suggest that diethyl phosphates and N-alkylcarbamates may be of value in future studies on the substrate specificities, regulation, and physiological role(s) of cholesteryl ester hydrolases.

Original languageEnglish (US)
Pages (from-to)2187-2193
Number of pages7
JournalJournal of lipid research
Volume31
Issue number12
StatePublished - 1990

Keywords

  • cholesterol
  • enzyme inhibition
  • hepatoma cells

ASJC Scopus subject areas

  • Endocrinology

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