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Journal of Lipid Research, Vol. 42, 501-508, April 2001
Copyright © 2001 by Lipid Research, Inc.

Original Article

Identification of a fatty acid ⁶-desaturase deficiency in human skin fibroblasts

Correspondence to: Arthur A. Spector, at the Department of Biochemistry, 4-403 BSB, University of Iowa, Iowa City, IA 52242., arthur-spector{at}uiowa.edu (E-mail)

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]-linolenic acid (18:3n-6), and [1-¹⁴C]dihomo--linolenic acid (20:3n-6), PUFA substrates that contain ⁶ double bonds. DF also contained 80% more 18:2n-6 and 25% less 20:4n-6. These results suggested that DF are deficient in ⁶ desaturation. This was confirmed by Northern blots demonstrating an 81;–94% decrease in ⁶-desaturase mRNA content in the DF cultures, whereas the ⁵-desaturase mRNA content was reduced by only 14%.

This is the first inherited abnormality in human PUFA metabolism shown to be associated with a ⁶-desaturase deficiency. Furthermore, the finding that the 18- and 24-carbon substrates are equally affected suggests that a single enzyme carries out both ⁶ 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 ⁶-desaturase deficiency in human skin fibroblasts. J. Lipid Res. 2001. 42: 501;–508.

Supplementary key words: polyunsaturated fatty acids, fatty acid desaturation, ⁵-desaturase, linoleic acid, -linolenic acid, arachidonic acid, docosahexaenoic acid, gene expression, genetic defect

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