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J. Biol. Chem., Vol. 278, Issue 48, 47594-47601, November 28, 2003

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Compared with Acyl-CoA:Cholesterol O-Acyltransferase (ACAT) 1 and Lecithin:Cholesterol Acyltransferase, ACAT2 Displays the Greatest Capacity to Differentiate Cholesterol from Sitosterol^*

Ryan E. Temel, Abraham K. Gebre, John S. Parks, and Lawrence L. Rudel

From the Department of Pathology, Section on Comparative Medicine, Wake Forest University School of Medicine, Winston-Salem, North Carolina 27157

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.

Received for publication, July 28, 2003 , and in revised form, September 9, 2003.

^* This work was supported in part by National Institutes of Health Grants HL 24736, HL 49373, and HL 54176. The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

Supported by National Institutes of Health Training Grant HL 07115. To whom correspondence may be addressed. Dept. of Pathology, Wake Forest University School of Medicine, Hanes Bldg., 6th Floor, Winston-Salem, NC 27157. Tel.: 336-716-2822; Fax: 336-716-6279; E-mail: rtemel{at}wfubmc.edu. To whom correspondence may be addressed: Dept. of Pathology, Wake Forest University School of Medicine, Hanes Bldg., 6th Floor, Winston-Salem, NC 27157. Tel.: 336-716-2821; Fax: 336-716-6279; E-mail: lrudel{at}wfubmc.edu.

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