Watts Jennifer L, Browse John
Institute of Biological Chemistry, Washington State University, Pullman, WA 99164-6340, USA.
Proc Natl Acad Sci U S A. 2002 Apr 30;99(9):5854-9. doi: 10.1073/pnas.092064799. Epub 2002 Apr 23.
Polyunsaturated fatty acids (PUFAs) are important membrane components and precursors of signaling molecules. To investigate the roles of these fatty acids in growth, development, and neurological function in an animal system, we isolated Caenorhabditis elegans mutants deficient in PUFA synthesis by direct analysis of fatty acid composition. C. elegans possesses all the desaturase and elongase activities to synthesize arachidonic acid and eicosapentaenoic acid from saturated fatty acid precursors. In our screen we identified mutants with defects in each fatty acid desaturation and elongation step of the PUFA biosynthetic pathway. The fatty acid compositions of the mutants reveal the substrate preferences of the desaturase and elongase enzymes and clearly demarcate the steps of this pathway. The mutants show that C. elegans does not require n3 or Delta5-unsaturated PUFAs for normal development under laboratory conditions. However, mutants with more severe PUFA deficiencies display growth and neurological defects. The mutants provide tools for investigating the roles of PUFAs in membrane biology and cell function in this animal model.
多不饱和脂肪酸（PUFAs）是重要的膜成分和信号分子的前体。为了研究这些脂肪酸在动物系统的生长、发育和神经功能中的作用，我们通过直接分析脂肪酸组成，分离出了缺乏PUFA合成能力的秀丽隐杆线虫突变体。秀丽隐杆线虫具备从饱和脂肪酸前体合成花生四烯酸和二十碳五烯酸所需的所有去饱和酶和延长酶活性。在我们的筛选中，我们鉴定出了在PUFA生物合成途径的每个脂肪酸去饱和和延长步骤中存在缺陷的突变体。这些突变体的脂肪酸组成揭示了去饱和酶和延长酶的底物偏好，并清晰地划分了该途径的各个步骤。这些突变体表明，在实验室条件下，秀丽隐杆线虫正常发育不需要n3或Δ5-不饱和PUFAs。然而，具有更严重PUFA缺陷的突变体表现出生长和神经缺陷。这些突变体为研究PUFAs在该动物模型的膜生物学和细胞功能中的作用提供了工具。
