Abstract | BACKGROUND: METHODOLOGY/PRINCIPAL FINDINGS: Analyzing MCF7 cell fatty acids with detailed structural mass spectrometry, we show that in the absence of FADS2 activity, the FADS1 product Δ5-desaturase operates to produce 5,11,14-20∶3 and 5,11,14,17-20∶4. These PUFA are missing the 8-9 double bond of the eicosanoid signaling precursors arachidonic acid (5,8,11,14-20∶4) and eicosapentaenoic acid (5,8,11,14,17-20∶5). Heterologous expression of FADS2 restores Δ6 and Δ8-desaturase activity and normal eicosanoid precursor synthesis. CONCLUSIONS/SIGNIFICANCE: The loss of FADS2-encoded activities in cancer cells shuts down normal PUFA biosynthesis, deleting the endogenous supply of eicosanoid and downstream docosanoid precursors, and replacing them with unusual butylene-interrupted fatty acids. If recapitulated in vivo, the normal eicosanoid and docosanoid cell signaling milieu would be depleted and altered due to reduction and substitution of normal substrates with unusual substrates, with unpredictable consequences for cellular communication.
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Authors | Woo Jung Park, Kumar S D Kothapalli, Peter Lawrence, J Thomas Brenna |
Journal | PloS one
(PLoS One)
Vol. 6
Issue 11
Pg. e28186
( 2011)
ISSN: 1932-6203 [Electronic] United States |
PMID | 22140540
(Publication Type: Journal Article)
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Chemical References |
- Delta-5 Fatty Acid Desaturase
- Eicosanoids
- Fatty Acid Desaturases
- FADS1 protein, human
- FADS2 protein, human
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Topics |
- Cell Line, Tumor
- Chromatography, Gas
- Chromosomes, Human, Pair 11
(genetics)
- Delta-5 Fatty Acid Desaturase
- Eicosanoids
(biosynthesis)
- Fatty Acid Desaturases
(metabolism)
- Genetic Loci
(genetics)
- Humans
- Lipid Metabolism
(genetics)
- Neoplasms
(genetics)
- Signal Transduction
- Transfection
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