Human very-long-chain acyl-CoA synthetase: Cloning, topography, and relevance to branched-chain fatty acid metabolism
Human very-long-chain acyl-CoA synthetase: Cloning, topography, and relevance to branched-chain fatty acid metabolism
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DOI：
10.1006/bbrc.1999.0510
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发表时间：
1999-04-13
影响因子：
3.1
通讯作者：
Watkins, PA
中科院分区：
文献类型：
--
作者：
Steinberg, SJ;Wang, SJ;Watkins, PA
极长链酰基辅酶A合成酶（VLCS）将含有22个或更多碳的极长链脂肪酸（VLCFA）激活为其辅酶A衍生物。我们克隆了编码大鼠肝酶（rVLCS）的基因的人类直系同源物（hVLCS）。 hVLCS 和 rVLCS 均含有 620 个氨基酸，主要在肝脏和肾脏中表达，并在其羧基末端具有潜在的过氧化物酶体靶向信号 1 (-LKL)。当在 COS-1 细胞中表达时，hVLCS 激活 VLCFA 二十四烷酸 (C24:0)、一种长链脂肪酸 (C16:0) 和两种支链脂肪酸：植烷酸和降植烷酸。免疫荧光和免疫印迹研究将 hVLCS 定位于过氧化物酶体和内质网。在 HepG2 细胞的过氧化物酶体中，hVLCS 在拓扑上面向基质而不是细胞质。这一方向，再加上 hVLCS 激活品牌链脂肪酸的观察结果，表明 hVLCS 可能在植烷酸α-氧化产生的降植烷酸的过氧化物酶体内再激活中发挥作用。 (C) 1999 年学术。
Very-long-chain acyl-CoA synthetases (VLCS) activate very-long-chain fatty acids (VLCFA) containing 22 or more carbons to their CoA derivatives. We cloned the human ortholog (hVLCS) of the gene encoding the rat liver enzyme (rVLCS). Both hVLCS and rVLCS contain 620 amino acids, are expressed primarily in liver and kidney, and have a potential peroxisome targeting signal 1 (-LKL) at their carboxy termini. When expressed in COS-1 cells, hVLCS activated the VLCFA lignoceric acid (C24:0), a long-chain fatty acid (C16:0), and two branched-chain fatty acids, phytanic acid and pristanic acid. Immunofluorescence and immunoblot studies localized hVLCS to both peroxisomes and endoplasmic reticulum. In peroxisomes of HepG2 cells, hVLCS was topographically oriented facing the matrix and not the cytoplasm. This orientation, coupled with the observation that hVLCS activates branded-chain fatty acids, suggests that hVLCS could play a role in the intraperoxisomal reactivation of pristanic acid produced via a-oxidation of phytanic acid. (C) 1999 Academic.