Identification of acyl coenzyme A:Monoacylglycerol acyltransferase 3, an intestinal specific enzyme implicated in dietary fat absorption
Identification of acyl coenzyme A:Monoacylglycerol acyltransferase 3, an intestinal specific enzyme implicated in dietary fat absorption
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DOI：
10.1074/jbc.c300042200
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发表时间：
2003-04-18
影响因子：
4.8
通讯作者：
Feder, JN
中科院分区：
文献类型：
--
作者：
Cheng, D;Nelson, TC;Feder, JN
酰基辅酶A：单酰基甘油酰基转移酶（MGAT）催化使用2-单酰基甘油和脂肪酰基辅酶A合成二酰基甘油。这种酶促反应被认为是小肠吸收脂肪的关键和限速步骤。虽然最近已经分离出第一个MGAT编码cDNA，命名为MGAT 1，但它不在小肠中表达，因此不能解释对脂肪吸收生理学重要的高肠MGAT酶活性。在目前的研究中，我们报告了一种新的MGAT的鉴定，命名为MGAT 3，并提出证据表明它符合难以捉摸的肠道MGAT的标准。MGAT 3编码一个与MGAT 1和MGAT 2高度同源的~ 36 kDa跨膜蛋白。在人类中，MGAT 3的表达限于胃肠道，在回肠中发现最高水平。在细胞水平，重组MGAT 3定位于内质网。在昆虫Sf`9细胞中产生的重组MGAT 3酶活性选择性地酰化2-单酰基甘油，其效率高于其他立体异构体。MGAT 3的分子鉴定将有助于评估使用肠道MGAT作为抗肥胖疗法的潜在干预点。
Acyl coenzyme A:monoacylglycerol acyltransferase (MGAT) catalyzes the synthesis of diacylglycerol using 2-monoacylglycerol and fatty acyl coenzyme A. This enzymatic reaction is believed to be an essential and rate-limiting step for the absorption of fat in the small intestine. Although the first MGAT-encoding cDNA, designated MGAT1, has been recently isolated, it is not expressed in the small intestine and hence cannot account for the high intestinal MGAT enzyme activity that is important for the physiology of fat absorption. In the current study, we report the identification of a novel MGAT, designated MGAT3, and present evidence that it fulfills the criteria to be the elusive intestinal MGAT. MGAT3 encodes a -36kDa transmembrane protein that is highly homologous to MGAT1 and -2. In humans, expression of MGAT3 is restricted to gastrointestinal tract with the highest level found in the ileum. At the cellular level, recombinant MGAT3 is localized to the endoplasmic reticulum. Recombinant MGAT3 enzyme activity produced in insect Sf`9 cells selectively acylates 2-monoacylglycerol with higher efficiency than other stereoisomers. The molecular identification of MGAT3 will facilitate the evaluation of using intestinal MGAT as a potential point of intervention for antiobesity therapies.