Microsomal fatty acyl-CoA transacylation and hydrolysis: fatty acyl-CoA species dependent modulation by liver fatty acyl-CoA binding proteins
Microsomal fatty acyl-CoA transacylation and hydrolysis: fatty acyl-CoA species dependent modulation by liver fatty acyl-CoA binding proteins
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DOI：
10.1016/s1388-1981(99)00170-5
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发表时间：
2000-01-03
影响因子：
4.8
通讯作者：
Schroeder, F
中科院分区：
文献类型：
--
作者：
Jolly, CA;Wilton, DC;Schroeder, F
肝脏和肠道胞浆中含有大量的长链脂肪酰辅酶A结合蛋白，如肝脏脂肪酸结合蛋白L和脂酰辅酶A结合蛋白。然而，这些蛋白质在微粒体中利用长链脂肪酰基-COAS(LCFA-COAS)进行甘油-3-磷酸顺序转酰化形成磷脂酸的相对功能和特异性尚不清楚。结果表明，L-乙酸甘油酯和乙酰胆碱分别使单不饱和油酰辅酶A和多不饱和花生四烯酰辅酶A的微粒体参入率分别提高8~10倍和2~3倍。相反，这两种蛋白质对饱和棕榈酰辅酶A的利用分别抑制了69%和62%。L-FABP和ACBP对微粒体磷脂酸生物合成的这种相似作用主要是通过速率限制步骤甘油-3-磷酸酰基转移酶的活性来调节的，而不是通过保护长链酰基-COAs的活性而不是通过保护微体水解酶的活性来实现的。事实上，ACBP而不是L-FABP对长链脂肪酰辅酶A水解酶活性的保护作用顺序为：棕榈酰辅酶A>；油酰辅酶A>；花生四烯酰辅酶A。综上所述，这些数据首次确定了L-FABP和ACBP在微粒体磷脂酸生物合成中的作用。通过优先刺激不饱和长链脂肪酰基辅酶A的微粒体转酰化，同时对微粒体酰基辅酶A水解酶起到区分保护作用，L-FABP和ACBP可以独特地调节脂肪酸酯化为磷脂酸的模式，磷脂酸是磷脂和三酰甘油的从头合成前体。这可能在一定程度上解释了这些蛋白质同时存在于参与脂肪酸吸收和脂蛋白分泌的细胞类型中。(C)2000 Elsevier Science B.V.保留所有权利。
Liver and intestinal cytosol contain abundant levels of long chain fatty acyl-CoA binding proteins such as liver fatty acid binding protein (L-FABP) and acyl-CoA binding protein (ACBP). However, the relative function and specificity of these proteins in microsomal utilization of long chain fatty acyl-CoAs (LCFA-CoAs) for sequential transacylation of glycerol-3-phosphate to form phosphatidic acid is not known. The results showed for the first time that L-FABP and ACBP both stimulated microsomal incorporation of the monounsaturated oleoyl-CoA and polyunsaturated arachidonoyl-CoA 8-10-fold and 2-3-fold, respectively. In contrast, these proteins inhibited microsomal utilization of the saturated palmitoyl-CoA by 69% and 62%, respectively. These similar effects of L-FABP and ACBP on microsomal phosphatidic acid biosynthesis were mediated primarily through the activity of glycerol-3-phosphate acyltransferase (GPAT), the rate limiting step, rather than by protecting the long chain acyl-CoAs from microsomal hydrolase activity. In fact, ACBP but not L-FABP protected long chain fatty acyl-CoAs from microsomal acyl-CoA hydrolase activity in the order: palmitoyl-CoA > oleoyl-CoA > arachidonoyl-CoA. In summary, the data established for the first time a role for both L-FABP and ACBP in microsomal phosphatidic acid biosynthesis. By preferentially stimulating microsomal transacylation of unsaturated long chain fatty acyl-CoAs while concomitantly exerting their differential protection from microsomal acyl-CoA hydrolase, L-FABP and ACBP can uniquely function in modulating the pattern of fatty acids esterified to phosphatidic acid, the de novo precursor of phospholipids and triacylglycerols. This may explain in part the simultaneous presence of these proteins in cell types involved in fatty acid absorption and lipoprotein secretion. (C) 2000 Elsevier Science B.V. All rights reserved.