Microsomal long chain fatty acyl-CoA transacylation: differential effect of sterol carrier protein-2

被引:17
作者
Chao, H
Billheimer, JT
Kier, AB
Schroeder, F [1 ]
机构
[1] Texas A&M Univ, Texas Vet Med Ctr, Dept Physiol & Pharmacol, College Stn, TX 77843 USA
[2] Texas A&M Univ, Texas Vet Med Ctr, Dept Pathol, College Stn, TX 77843 USA
[3] DuPont Co Inc, Pharmaceut, Cardiovasc Dept, Expt Stn 4003231, Wilmington, DE 19898 USA
来源
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR AND CELL BIOLOGY OF LIPIDS | 1999年 / 1439卷 / 03期
关键词
microsome; sterol carrier protein-2;
D O I
10.1016/S1388-1981(99)00109-2
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
The recent discovery that sterol carrier protein-2 (SCP-2) binds long chain fatty acyl-CoA (LCFA-CoA) with high affinity (A. Frolov et al., J. Biol. Chem. 271 (1997) 31878-31884) suggests new possible functions of this protein in LCFA-CoA metabolism. The purpose of the present investigation was to determine whether SCP-2 differentially modulated microsomal LCFA-CoA transacylation to cholesteryl esters, triacylglycerols, and phospholipids in vitro. Microsomal acyl-CoA:cholesterol acyltransferase (ACAT) activity measured with liposomal membrane cholesterol donors depended on substrate LCFA-CoA level, mol% cholesterol in the liposomal. membrane, and total amount of liposomal cholesterol. As compared to basal activity Without liposomes, microsomal ACAT was inhibited 30-50% in the presence of cholesterol poor (1.4 mol%) liposomes. In contrast, cholesterol rich (> 25 mol%) liposomes stimulated ACAT up to 6.4-fold compared to basal activity without liposomes and nearly 10-fold as compared to cholesterol poor (1.4 mol%) liposomes. Increasing oleoyl-CoA reversed the inhibition of microsomal ACAT by cholesterol poor (1.4 mol%) liposomes, but did not further stimulate ACAT in the presence of cholesterol rich (35 mol%) liposomes. In contrast, high (100 mu M) oleoyl-CoA inhibited ACAT nearly 3-fold. This inhibition was reversed by LCFA-CoA binding proteins, bovine serum albumin (BSA) and SCP-2. SCP-2 was 10-fold more effective (mole for mole) than BSA in reversing LCFA-CoA inhibited microsomal ACAT. Concomitantly, under conditions in which SCP-2 stimulated ACAT it equally enhanced transacylation of oleoyl-CoA into phospholipids, and 5.2-fold enhanced oleoyl-CoA transacylation to triacylglycerols. In summary, SCP-2 appeared to exert its greatest effects on microsomal transacylation in vitro by reversing LCFA-CoA inhibition of ACAT and by differentially targeting LCFA-CoA to triacylglycerols. These data suggest that the high affinity interaction of SCP-2s with LCFA-CoA may be physiologically important in microsomal transacylation reactions. (C) 1999 Elsevier Science B.V. All rights reserved.
引用
收藏
页码:371 / 383
页数:13
相关论文
共 71 条
[1]  
Atshaves BP, 1999, J LIPID RES, V40, P610
[2]   Lipid binding to sterol carrier protein-2 is inhibited by ethanol [J].
Avdulov, NA ;
Chochina, SV ;
Igbavboa, U ;
Warden, CS ;
Schroeder, F ;
Wood, WG .
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR AND CELL BIOLOGY OF LIPIDS, 1999, 1437 (01) :37-45
[3]   SUBMICROSOMAL LOCALIZATION OF ACYL-COENZYME A-CHOLESTEROL ACYLTRANSFERASE AND ITS SUBSTRATE, AND OF CHOLESTERYL ESTERS IN RAT-LIVER [J].
BALASUBRAMANIAM, S ;
VENKATESAN, S ;
MITROPOULOS, KA ;
PETERS, TJ .
BIOCHEMICAL JOURNAL, 1978, 174 (03) :863-872
[4]  
BAN T, 1991, ARTERY, V18, P54
[5]   PHOSPHOLIPID-TRANSFER PROTEINS AND THEIR MESSENGER-RNAS IN DEVELOPING RAT LUNG AND IN ALVEOLAR TYPE-II CELLS [J].
BATENBURG, JJ ;
OSSENDORP, BC ;
SNOEK, GT ;
WIRTZ, KWA ;
HOUWELING, M ;
ELFRING, RH .
BIOCHEMICAL JOURNAL, 1994, 298 :223-229
[6]   Sterol carrier protein-2 overexpression enhances sterol cycling and inhibits cholesterol ester synthesis and high density lipoprotein cholesterol secretion [J].
Baum, CL ;
Reschly, EJ ;
Gayen, AK ;
Groh, ME ;
Schadick, K .
JOURNAL OF BIOLOGICAL CHEMISTRY, 1997, 272 (10) :6490-6498
[7]  
BAUM CL, 1993, J LIPID RES, V34, P729
[8]  
Billheimer J T, 1990, Subcell Biochem, V16, P301
[9]  
BILLHEIMER JT, 1985, METHOD ENZYMOL, V3, P286
[10]  
BILLHEIMER JT, 1990, ADV CHOLESTEROL RES, P7