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Docosahexaenoic acid synthesis in human skin fibroblasts involves peroxisomal retroconversion of tetracosahexaenoic acid
Open accessAbstract
The purpose of this study was to determine whether the formation of docosahexaenoic acid in human cells occurs through a pathway that involves 24-carbon n-3 fatty acid intermediates and retroconversion. Normal human skin fibroblasts synthesized radiolabeled docosahexaenoic acid from [1-(14)C]18:3n-3, [3-(14)C]22:5n-3, [3-(14)C]24:5n-3, and [3-(14)C]24:6n-3. The amount of docosahexaenoate formed was reduced in fibroblasts defective in peroxisomal biogenesis, by 90-100% in Zellweger's syndrome and by 50-75% in infantile Refsum's disease. Fatty acid elongation and desaturation were intact in these mutant cells. No decrease in radiolabeled docosahexaenoic acid production occurred in mutant fibroblasts defective in peroxisomal alpha-oxidation or mitochondrial beta-oxidation, or in normal fibroblasts treated with methyl palmoxirate to inhibit mitochondrial beta-oxidation. Therefore, the retroconversion step in docosahexaenoic acid formation occurs through peroxisomal beta-oxidation in normal human cells. These results demonstrate that the pathway for docosahexaenoic acid synthesis in human cells involves 24-carbon intermediates. The limited ability to synthesize docosahexaenoic acid may underlie some of the pathology that occurs in genetic diseases involving peroxisomal beta-oxidation.
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Cited by
Fatty acid elongases in mammals: their regulation and roles in metabolism
JAKOBSSON, A., WESTERBERG, R., & JACOBSSON, A. (2006) · Progress in Lipid Research · doi:10.1016/j.plipres.2006.01.004 · Cited by 936
Dyall, S. C. (2015) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2015.00052 · Cited by 943
Peroxisome biogenesis disorders
Steinberg, S. J., Dodt, G., Raymond, G. V., Braverman, N. E., Moser, A. B., & Moser, H. W. (2006) · Biochimica et Biophysica Acta (BBA) - Molecular Cell Research · doi:10.1016/j.bbamcr.2006.09.010 · Cited by 522
Bergé, J.-P., & Barnathan, G. (2005) · Advances in Biochemical Engineering/Biotechnology · doi:10.1007/b135782 · Cited by 401
Polyunsaturated fatty acid synthesis: What will they think of next?
Wallis, J. G., Watts, J. L., & Browse, J. (2002) · Trends in Biochemical Sciences · doi:10.1016/s0968-0004(02)02168-0 · Cited by 375
Metadata
- Authors
- Moore, S. A., Hurt, E., Yoder, E., Sprecher, H., & Spector, A. A.
- Venue
- Journal of Lipid Research
- Publisher
- Elsevier BV
- Published
- 1995-11
- Volume
- 36
- Issue
- 11
- Pages
- 2433-2443
- ISSN
- 0022-2275 (ISSN-L)
- OpenAlex
- W2186476960
- Cited by
- 170
- References
- 0
- FWCI
- 13.97
- Type
- journal article
- Language
- en
- Open access
- hybrid
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- CoChat. (2026). Citation check: Docosahexaenoic acid synthesis in human skin fibroblasts involves peroxisomal retroconversion of tetracosahexaenoic acid. https://app.cochat.ai/papers/10.1016/s0022-2275(20)39724-8
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- Moore, S. A., Hurt, E., Yoder, E., Sprecher, H., & Spector, A. A. (1995). Docosahexaenoic acid synthesis in human skin fibroblasts involves peroxisomal retroconversion of tetracosahexaenoic acid. Journal of Lipid Research. https://doi.org/10.1016/s0022-2275(20)39724-8
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