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标题：Identification of a fatty acid Δ6-desaturase deficiency in human skin fibroblasts
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作者：Deborah E. Williard ; Joseph O. Nwankwo ; Terry L. Kaduce 等
期刊名称：JLR Papers In Press
印刷版ISSN：0022-2275
电子版ISSN：1539-7262
出版年度：2001
卷号：42
期号：4
页码：501-508
语种：English
出版社：American Society for Biochemistry and Molecular Biology
摘要：Polyunsaturated fatty acid (PUFA) utilization was investigated in skin fibroblasts cultured from a female patient with an inherited abnormality in lipid metabolism. These deficient human skin fibroblasts (DF) converted 85–95% less [1-¹⁴C]linoleic acid (18:2n-6) to arachidonic acid (20:4n-6), 95% less [3-¹⁴C]tetracosatetraenoic acid (24:4n-6) to docosapentaenoic acid (22:5n-6), and 95% less [1-¹⁴C]-linolenic acid (18:3n-3) and [3-¹⁴C]tetracosapentaenoic acid (24:5n-3) to docosahexaenoic acid (22:6n-3) than did normal human skin fibroblasts (NF). The only product formed by the DF cultures from [1-¹⁴C]tetradecadienoic acid (14:2n-6) was 18:2n-6. However, they produced 50–90% as much 20:4n-6 as the NF cultures from [1-¹⁴C]hexadecatrienoic acid (16:3n-6), [1-¹⁴C]γ-linolenic acid (18:3n-6), and [1-¹⁴C]dihomo-γ-linolenic acid (20:3n-6), PUFA substrates that contain Δ⁶ double bonds. DF also contained 80% more 18:2n-6 and 25% less 20:4n-6. These results suggested that DF are deficient in Δ⁶ desaturation. This was confirmed by Northern blots demonstrating an 81–94% decrease in Δ⁶-desaturase mRNA content in the DF cultures, whereas the Δ⁵-desaturase mRNA content was reduced by only 14%. This is the first inherited abnormality in human PUFA metabolism shown to be associated with a Δ⁶-desaturase deficiency. Furthermore, the finding that the 18- and 24-carbon substrates are equally affected suggests that a single enzyme carries out both Δ⁶ desaturation reactions in human PUFA metabolism. —Williard, D. E., J. O. Nwankwo, T. L. Kaduce, S. D. Harmon, M. Irons, H. W. Moser, G. V. Raymond, and A. A. Spector. Identification of a fatty acid Δ⁶-desaturase deficiency in human skin fibroblasts. J. Lipid Res. 2001. 42: 501–508.
关键词：polyunsaturated fatty acids ; fatty acid desaturation ; Δ⁵-desaturase ; linoleic acid ; α-linolenic acid ; arachidonic acid ; docosahexaenoic acid ; gene expression ; genetic defect