Rat Carboxylesterase ES-4 Enzyme Functions as a Major Hepatic Neutral Cholesteryl Ester Hydrolase

Although esterification of free cholesterol to cholesteryl ester in the liver is known to be catalyzed by the enzyme acyl-coenzyme A:cholesterol acyltransferase, ACAT, the neutral cholesteryl ester hydrolase (nCEH) that catalyzes the reverse reaction has remained elusive. Because cholesterol undergo...

Full description

Saved in:
Bibliographic Details
Published in:The Journal of biological chemistry 2011-11, Vol.286 (46), p.39683-39692
Main Authors: Parathath, Saj, Dogan, Snjezana, Joaquin, Victor A., Ghosh, Snigdha, Guo, Liang, Weibel, Ginny L., Rothblat, George H., Harrison, Earl H., Fisher, Edward A.
Format: Article
Language:English
Subjects:
Animals
Carboxylesterase - genetics
Carboxylesterase - metabolism
Cell Line, Tumor
Cholesterol - genetics
Cholesterol - metabolism
Hepatocyte
Hepatocytes - enzymology
Hydrolases
Hydrolysis
Lipids
Liver
Liver - enzymology
Mice
Rat
Rats
Rats, Sprague-Dawley
Sterol Esterase - genetics
Sterol Esterase - metabolism
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Although esterification of free cholesterol to cholesteryl ester in the liver is known to be catalyzed by the enzyme acyl-coenzyme A:cholesterol acyltransferase, ACAT, the neutral cholesteryl ester hydrolase (nCEH) that catalyzes the reverse reaction has remained elusive. Because cholesterol undergoes continuous cycling between free and esterified forms, the steady-state concentrations in the liver of the two species and their metabolic availability for pathways, such as lipoprotein assembly and bile acid synthesis, depend upon nCEH activity. On the basis of the general characteristics of the family of rat carboxylesterases, we hypothesized that one member, ES-4, was a promising candidate as a hepatic nCEH. Using under- and overexpression approaches, we provide multiple lines of evidence that establish ES-4 as a bona fide endogenous nCEH that can account for the majority of cholesteryl ester hydrolysis in transformed rat hepatic cells and primary rat hepatocytes.
ISSN:0021-9258
1083-351X
DOI:10.1074/jbc.M111.258095