Identification of two mammalian reductases involved in the two-carbon fatty acyl elongation cascade
Identification of two mammalian reductases involved in the two-carbon fatty acyl elongation cascade
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DOI：
10.1074/jbc.m211684200
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发表时间：
2003-02-28
影响因子：
4.8
通讯作者：
Horton, JD
中科院分区：
文献类型：
--
作者：
Moon, YA;Horton, JD
脂肪酸的从头合成发生在两个不同的细胞隔室中。棕榈酸（16：0）是在细胞质中通过乙酰辅酶A羧化酶1和脂肪酸合成酶由乙酰辅酶A和丙二酰辅酶A合成的。超过16个碳的脂肪酸的合成发生在微粒体中，并利用丙二酰辅酶A作为碳源。每个两碳加成需要四个连续反应：缩合、还原、脱水和最终还原以形成延长的脂肪酰辅酶A。初始缩合反应是微粒体脂肪酰基延伸的调节和速率控制步骤。我们先前报道了小鼠长链脂肪酰基延长酶的cDNA克隆和表征。(LCE)（一）. LCE在细胞中的过表达导致了C12-C16脂肪酸的二碳单元的增加，并且提供了LCE催化长链脂肪酸延伸的初始缩合反应的证据。延伸反应中的其余三种酶尚未在哺乳动物中鉴定。在这里，我们报告的鉴定和表征的两种哺乳动物的酶，催化3-酮脂酰辅酶A和反式-2，3-烯酰辅酶A还原反应，在长链和非常长的链脂肪酸延长，分别。
The de novo synthesis of fatty acids occurs in two distinct cellular compartments. Palmitate (16:0) is synthesized from acetyl-CoA and malonyl-CoA in the cytoplasm by the enzymes acetyl-CoA carboxylase 1 and fatty acid synthase. The synthesis of fatty acids longer than 16 carbons takes place in microsomes and utilizes malonyl-CoA as the carbon source. Each two-carbon addition requires four sequential reactions: condensation, reduction, dehydration, and a final reduction to form the elongated fatty acyl-CoA. The initial condensation reaction is the regulated and rate-controlling step in microsomal fatty acyl elongation. We previously reported the cDNA cloning and characterization of a murine long chain fatty acyl elongase.(LCE) (1). Overexpression of LCE in cells resulted in the enhanced addition of two-carbon units to C12-C16 fatty acids, and evidence was provided that LCE catalyzed the initial condensation reaction of long chain fatty acid elongation. The remaining three enzymes in the elongation reaction have not been identified in mammals. Here, we report the identification and characterization of two mammalian enzymes that catalyze the 3-ketoacyl-CoA and trans-2,3-enoyl-CoA reduction reactions in long and very long chain fatty acid elongation, respectively.