Hastings N, Agaba M, Tocher D R, Leaver M J, Dick J R, Sargent J R, Teale A J
Institute of Aquaculture, University of Stirling, Stirling FK9 4LA, Scotland.
Proc Natl Acad Sci U S A. 2001 Dec 4;98(25):14304-9. doi: 10.1073/pnas.251516598. Epub 2001 Nov 27.
Delta5 and Delta6 fatty acid desaturases are critical enzymes in the pathways for the biosynthesis of the polyunsaturated fatty acids arachidonic, eicosapentaenoic, and docosahexaenoic acids. They are encoded by distinct genes in mammals and Caenorhabditis elegans. This paper describes a cDNA isolated from zebrafish (Danio rerio) with high similarity to mammalian Delta6 desaturase genes. The 1,590-bp sequence specifies a protein that, in common with other fatty acid desaturases, contains an N-terminal cytochrome b(5) domain and three histidine boxes, believed to be involved in catalysis. When the zebrafish cDNA was expressed in Saccharomyces cerevisiae it conferred the ability to convert linoleic acid (18:2n-6) and alpha-linolenic acid (18:3n-3) to their corresponding Delta6 desaturated products, 18:3n-6 and 18:4n-3. However, in addition it conferred on the yeast the ability to convert di-homo-gamma-linoleic acid (20:3n-6) and eicosatetraenoic acid (20:4n-3) to arachidonic acid (20:4n-6) and eicosapentaenoic acid (20:5n-3), respectively, indicating that the zebrafish gene encodes an enzyme having both Delta5 and Delta6 desaturase activity. The zebrafish Delta5/Delta6 desaturase may represent a component of a prototypic vertebrate polyunsaturated fatty acids biosynthesis pathway.
Δ5和Δ6脂肪酸去饱和酶是多不饱和脂肪酸花生四烯酸、二十碳五烯酸和二十二碳六烯酸生物合成途径中的关键酶。它们由哺乳动物和秀丽隐杆线虫中的不同基因编码。本文描述了从斑马鱼（Danio rerio）中分离出的一种与哺乳动物Δ6去饱和酶基因高度相似的cDNA。这个1590bp的序列编码一种蛋白质，与其他脂肪酸去饱和酶一样，它含有一个N端细胞色素b5结构域和三个组氨酸盒，据信这些结构域参与催化作用。当斑马鱼cDNA在酿酒酵母中表达时，它赋予了将亚油酸（18:2n-6）和α-亚麻酸（18:3n-3）转化为其相应的Δ6去饱和产物18:3n-6和18:4n-3的能力。然而，此外它还赋予酵母将二高-γ-亚麻酸（20:3n-6）和二十碳四烯酸（20:4n-3）分别转化为花生四烯酸（20:4n-6）和二十碳五烯酸（20:5n-3）的能力，这表明斑马鱼基因编码一种具有Δ5和Δ6去饱和酶活性的酶。斑马鱼的Δ5/Δ6去饱和酶可能代表了原型脊椎动物多不饱和脂肪酸生物合成途径的一个组成部分。
