Document Detail


Compared with Acyl-CoA:cholesterol O-acyltransferase (ACAT) 1 and lecithin:cholesterol acyltransferase, ACAT2 displays the greatest capacity to differentiate cholesterol from sitosterol.
MedLine Citation:
PMID:  12975367     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The capacity of acyl-CoA:cholesterol O-acyltransferase (ACAT) 2 to differentiate cholesterol from the plant sterol, sitosterol, was compared with that of the sterol esterifying enzymes, ACAT1 and lecithin:cholesterol acyltransferase (LCAT). Cholesterol-loaded microsomes from transfected cells containing either ACAT1 or ACAT2 exhibited significantly more ACAT activity than their sitosterol-loaded counterparts. In sitosterol-loaded microsomes, both ACAT1 and ACAT2 were able to esterify sitosterol albeit with lower efficiencies than cholesterol. The mass ratios of cholesterol ester to sitosterol ester formed by ACAT1 and ACAT2 were 1.6 and 7.2, respectively. Compared with ACAT1, ACAT2 selectively esterified cholesterol even when sitosterol was loaded into the microsomes. To further characterize the difference in sterol specificity, ACAT1 and ACAT2 were compared in intact cells loaded with either cholesterol or sitosterol. Despite a lower level of ACAT activity, the ACAT1-expressing cells esterified 4-fold more sitosterol than the ACAT2 cells. The data showed that compared with ACAT1, ACAT2 displayed significantly greater selectively for cholesterol compared with sitosterol. The plasma cholesterol esterification enzyme lecithin:cholesterol acyltransferase was also compared. With recombinant high density lipoprotein particles, the esterification rate of cholesterol by LCAT was only 15% greater than for sitosterol. Thus, LCAT was able to efficiently esterify both cholesterol and sitosterol. In contrast, ACAT2 demonstrated a strong preference for cholesterol rather than sitosterol. This sterol selectivity by ACAT2 may reflect a role in the sorting of dietary sterols during their absorption by the intestine in vivo.
Authors:
Ryan E Temel; Abraham K Gebre; John S Parks; Lawrence L Rudel
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Publication Detail:
Type:  Journal Article; Research Support, U.S. Gov't, P.H.S.     Date:  2003-09-15
Journal Detail:
Title:  The Journal of biological chemistry     Volume:  278     ISSN:  0021-9258     ISO Abbreviation:  J. Biol. Chem.     Publication Date:  2003 Nov 
Date Detail:
Created Date:  2003-11-24     Completed Date:  2004-01-12     Revised Date:  2007-11-14    
Medline Journal Info:
Nlm Unique ID:  2985121R     Medline TA:  J Biol Chem     Country:  United States    
Other Details:
Languages:  eng     Pagination:  47594-601     Citation Subset:  IM    
Affiliation:
Department of Pathology, Section on Comparative Medicine, Wake Forest University School of Medicine, Winston-Salem, North Carolina 27157, USA. rtemel@wfubmc.edu
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MeSH Terms
Descriptor/Qualifier:
Animals
Cell Line
Cercopithecus aethiops
Cholesterol / chemistry*,  metabolism
Cyclodextrins / chemistry
Esters / chemistry
Lipoproteins, HDL / chemistry
Mice
Microsomes / metabolism
Phosphatidylcholines / chemistry*
Recombinant Proteins / chemistry
Sitosterols / chemistry*
Sterol O-Acyltransferase / metabolism,  physiology*
Time Factors
Transfection
beta-Cyclodextrins*
Grant Support
ID/Acronym/Agency:
HL 24736/HL/NHLBI NIH HHS; HL 49373/HL/NHLBI NIH HHS; HL 54176/HL/NHLBI NIH HHS; HL-07115/HL/NHLBI NIH HHS
Chemical
Reg. No./Substance:
0/Cyclodextrins; 0/Esters; 0/Lipoproteins, HDL; 0/Phosphatidylcholines; 0/Recombinant Proteins; 0/Sitosterols; 0/beta-Cyclodextrins; 57-88-5/Cholesterol; 5779-62-4/sitosterol; 94035-02-6/2-hydroxypropyl-beta-cyclodextrin; EC 2.3.1.26/Sterol O-Acyltransferase; EC 2.3.1.26/sterol O-acyltransferase 2

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