Cloning, expression, and characterization of the human mitochondrial beta-ketoacyl synthase. Complementation of the yeast CEM1 knock-out strain.
Cloning, expression, and characterization of the human mitochondrial beta-ketoacyl synthase. Complementation of the yeast CEM1 knock-out strain.
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DOI：
10.1074/jbc.m413686200
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发表时间：
2005-04
期刊：
影响因子：
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通讯作者：
Lei Zhang;A. Joshi;Jörg Hofmann;E. Schweizer;Stuart Smith
中科院分区：
文献类型：
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作者：
Lei Zhang;A. Joshi;Jörg Hofmann;E. Schweizer;Stuart Smith
一种涉及脂肪酸合成线粒体途径的人β -酮酰合成酶已被鉴定、克隆、表达和表征。序列分析表明，该蛋白与原核生物和叶绿体中发现的独立对应物的关系比与人胞质脂肪酸合成酶的β -酮酰合成酶结构域的关系更密切。全长核编码459残基蛋白包括约38个残基的n端序列元件，其功能是线粒体靶向序列。该酶可以延长含有2-14个碳原子的酰基链，丙二醇基部分以硫酯连接到人线粒体酰基载体蛋白上，能够恢复呼吸缺陷酵母突变体cem1的生长，该突变体缺乏内源性线粒体β -酮酰基合成酶，硫辛酸水平降低。迄今为止，已经在人类中确定了假定的II型线粒体脂肪酸合成酶途径的四个组成部分：酰基载体蛋白、丙二醇基转移酶、β -酮酰基合成酶和烯酰还原酶。β -酮酰合成酶的底物特异性和互补数据表明，与植物和真菌一样，在人类中，该途径可能在辛烷酰酰基载体蛋白、硫辛酸前体以及最佳线粒体功能所需的长链脂肪酸的生成中发挥重要作用。
A human beta-ketoacyl synthase implicated in a mitochondrial pathway for fatty acid synthesis has been identified, cloned, expressed, and characterized. Sequence analysis indicates that the protein is more closely related to freestanding counterparts found in prokaryotes and chloroplasts than it is to the beta-ketoacyl synthase domain of the human cytosolic fatty acid synthase. The full-length nuclear-encoded 459-residue protein includes an N-terminal sequence element of approximately 38 residues that functions as a mitochondrial targeting sequence. The enzyme can elongate acyl-chains containing 2-14 carbon atoms with malonyl moieties attached in thioester linkage to the human mitochondrial acyl carrier protein and is able to restore growth to the respiratory-deficient yeast mutant cem1 that lacks the endogenous mitochondrial beta-ketoacyl synthase and exhibits lowered lipoic acid levels. To date, four components of a putative type II mitochondrial fatty acid synthase pathway have been identified in humans: acyl carrier protein, malonyl transferase, beta-ketoacyl synthase, and enoyl reductase. The substrate specificity and complementation data for the beta-ketoacyl synthase suggest that, as in plants and fungi, in humans this pathway may play an important role in the generation of octanoyl-acyl carrier protein, the lipoic acid precursor, as well as longer chain fatty acids that are required for optimal mitochondrial function.