Identification of a fatty acid Δ6-desaturase deficiency in human skin fibroblasts

D. E. Williard, J. O. Nwankwo, T. L. Kaduce, S. D. Harmon, M. Irons, H. W. Moser, Gerald Raymond, A. A. Spector

Research output: Contribution to journalArticle

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Abstract

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 Δ6desaturase 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.

Original languageEnglish (US)
Pages (from-to)501-508
Number of pages8
JournalJournal of Lipid Research
Volume42
Issue number4
StatePublished - May 5 2001

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Fatty Acid Desaturases
Fibroblasts
Unsaturated Fatty Acids
alpha-Linolenic Acid
Skin
Fatty Acids
Metabolism
Messenger RNA
Acids
Docosahexaenoic Acids
Linoleic Acid
Substrates
Lipid Metabolism
Arachidonic Acid
Northern Blotting
Carbon
Enzymes

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Endocrinology
  • Cell Biology

Cite this

Williard, D. E., Nwankwo, J. O., Kaduce, T. L., Harmon, S. D., Irons, M., Moser, H. W., ... Spector, A. A. (2001). Identification of a fatty acid Δ6-desaturase deficiency in human skin fibroblasts. Journal of Lipid Research, 42(4), 501-508.
Williard, D. E. ; Nwankwo, J. O. ; Kaduce, T. L. ; Harmon, S. D. ; Irons, M. ; Moser, H. W. ; Raymond, Gerald ; Spector, A. A. / Identification of a fatty acid Δ6-desaturase deficiency in human skin fibroblasts. In: Journal of Lipid Research. 2001 ; Vol. 42, No. 4. pp. 501-508.
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abstract = "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 Δ6desaturase 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.",
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Williard, DE, Nwankwo, JO, Kaduce, TL, Harmon, SD, Irons, M, Moser, HW, Raymond, G & Spector, AA 2001, 'Identification of a fatty acid Δ6-desaturase deficiency in human skin fibroblasts', Journal of Lipid Research, vol. 42, no. 4, pp. 501-508.

Identification of a fatty acid Δ6-desaturase deficiency in human skin fibroblasts. / Williard, D. E.; Nwankwo, J. O.; Kaduce, T. L.; Harmon, S. D.; Irons, M.; Moser, H. W.; Raymond, Gerald; Spector, A. A.

In: Journal of Lipid Research, Vol. 42, No. 4, 05.05.2001, p. 501-508.

Research output: Contribution to journalArticle

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T1 - Identification of a fatty acid Δ6-desaturase deficiency in human skin fibroblasts

AU - Williard, D. E.

AU - Nwankwo, J. O.

AU - Kaduce, T. L.

AU - Harmon, S. D.

AU - Irons, M.

AU - Moser, H. W.

AU - Raymond, Gerald

AU - Spector, A. A.

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N2 - 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 Δ6desaturase 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.

AB - 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 Δ6desaturase 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.

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Williard DE, Nwankwo JO, Kaduce TL, Harmon SD, Irons M, Moser HW et al. Identification of a fatty acid Δ6-desaturase deficiency in human skin fibroblasts. Journal of Lipid Research. 2001 May 5;42(4):501-508.