# Linoleoyl-CoA desaturase
**Linoleoyl-CoA desaturase** (also called Δ6-desaturase, delta-6 fatty acid desaturase, or acyl-CoA 6-desaturase) is an enzyme that catalyzes the syn-dehydrogenation of linoleoyl-CoA to gamma-linolenoyl-CoA, introducing a cis double bond at carbon 6 of the fatty acyl chain. Its current [Enzyme Commission number](https://www.edgepedia.org/enzyme-commission-number) is EC 1.14.19.3; it was formerly characterized as EC 1.14.99.25.[1](https://meshb.nlm.nih.gov/record/ui?dcmsLinks=true&ui=D050602) In humans the enzyme is encoded by the FADS2 gene.[2](https://www.uniprot.org/uniprotkb/O95864-3/entry)
| Key fact | Detail |
|---|---|
| Reaction | Syn-dehydrogenation of linoleoyl-CoA to gamma-linolenoyl-CoA; a cis double bond is inserted at carbon 6, between a pre-existing double bond and the carboxyl end of the chain[1](https://meshb.nlm.nih.gov/record/ui?dcmsLinks=true&ui=D050602) • [3](https://zfin.org/ZDB-TERM-091209-10155) |
| EC number | EC 1.14.19.3 (formerly EC 1.14.99.25)[1](https://meshb.nlm.nih.gov/record/ui?dcmsLinks=true&ui=D050602) |
| Human gene / protein | FADS2, acyl-CoA 6-desaturase, 444 amino acids, reviewed with evidence at protein level[2](https://www.uniprot.org/uniprotkb/O95864-3/entry) |
| Physiological role | Catalyzes the first and rate-limiting step in biosynthesis of highly unsaturated fatty acids from the essential polyunsaturated fatty acids linoleic acid (18:2n-6) and alpha-linolenic acid (18:3n-3)[2](https://www.uniprot.org/uniprotkb/O95864-3/entry) |
| Electron donor | Cytochrome b5, oxidized from Fe(II) to Fe(III) during the reaction, serves as the electron donor to the desaturase active site[3](https://zfin.org/ZDB-TERM-091209-10155) • [4](https://www.creative-enzymes.com/downpdf.php?pid=11163) • [10](https://www.kegg.jp/entry/R11043) |
| MeSH status | Indexed as its own descriptor since 2006; previously indexed under Fatty Acid Desaturases from 1981 to 2005[1](https://meshb.nlm.nih.gov/record/ui?dcmsLinks=true&ui=D050602) |
## Reaction and mechanism
The [Gene Ontology](https://www.edgepedia.org/gene-ontology) term for the enzyme's molecular function defines the reaction for the linoleoyl-CoA substrate as (9Z,12Z)-octadecadienoyl-CoA + 2 Fe(II)-[cytochrome b5] + 2 H+ + O2 = (6Z,9Z,12Z)-octadecatrienoyl-CoA + 2 Fe(III)-[cytochrome b5] + 2 H2O, and for the alpha-linolenoyl-CoA substrate as (9Z,12Z,15Z)-octadecatrienoyl-CoA + 2 Fe(II)-[cytochrome b5] + O2 + 2 H+ = (6Z,9Z,12Z,15Z)-octadecatetraenoyl-CoA + 2 Fe(III)-[cytochrome b5] + 2 H2O.[3](https://zfin.org/ZDB-TERM-091209-10155) The enzyme is thus a mixed-function oxygenase within the fatty acid desaturase family, whose members catalyze syn-dehydrogenation reactions linked directly to the reduction of molecular oxygen.[1](https://meshb.nlm.nih.gov/record/ui?dcmsLinks=true&ui=D050602) • [5](https://www.ncbi.nlm.nih.gov/mesh?Cmd=DetailsSearch&Db=mesh&Term=%22Fatty+Acid+Desaturases%22%5BMeSH+Terms%5D) A cytochrome b5 domain is present in the enzyme and is thought to supply electrons to the active site in vivo.[4](https://www.creative-enzymes.com/downpdf.php?pid=11163)
## Role in polyunsaturated fatty acid biosynthesis
[Linoleic acid](https://www.edgepedia.org/linoleic-acid) (LA, 18:2n-6) and alpha-linolenic acid (ALA, 18:3n-3) are essential polyunsaturated fatty acids that animals must obtain from the diet. The Δ6-desaturation step converts LA into gamma-linoleate (GLA, 18:3n-6) and ALA into stearidonate (18:4n-3), and this step is the first and rate-limiting step of the pathway that builds highly unsaturated fatty acids (HUFA).[2](https://www.uniprot.org/uniprotkb/O95864-3/entry) Within the n-3 pathway, the enzyme additionally converts tetracosapentaenoate (24:5n-3) into tetracosahexaenoate (24:6n-3); this product then becomes docosahexaenoate (DHA, 22:6n-3), a lipid vital to nervous system functioning.[2](https://www.uniprot.org/uniprotkb/O95864-3/entry) The related Δ5 fatty acid desaturase acts later in the same pathway, converting [dihomo-gamma-linolenic acid](https://www.edgepedia.org/dihomo-gamma-linolenic-acid) toward arachidonic acid.[6](https://meshb.nlm.nih.gov/record/ui?dcmsLinks=true&ui=D000090943)
## Substrate carrier specificity
Desaturases differ in which acyl carrier they act on. Acyl-CoA desaturases are found in fungal and animal cells, where double bonds are introduced on coenzyme A thioesters, while plants use acyl-ACP and acyl-lipid desaturases.[7](https://pmc.ncbi.nlm.nih.gov/articles/PMC5816129/) Reconstitution experiments in yeast showed that plant and fungal Δ6-desaturases act on fatty acid acylated at the sn-2 position of phosphatidylcholine, and this specificity, together with limited re-equilibration with the acyl-CoA pool, leads to accumulation of gamma-linolenic acid and prevents efficient arachidonic acid biosynthesis in yeast. The human Δ6-desaturase, in contrast, uses linoleoyl-CoA as its substrate, which results in high efficiency of the subsequent elongation step.[8](https://www.sciencedirect.com/science/article/pii/S0021925820835674)
## Regulation
In animals, expression of Δ9 and Δ6 acyl-CoA desaturases is controlled by hormones such as insulin, and the sterol regulatory element-binding protein (SREBP) pathway controls the level of expression of Δ9, Δ5, and Δ6 desaturases.[9](https://onlinelibrary.wiley.com/doi/pdfdirect/10.1002/iub.2671)
## Nomenclature
The enzyme carries many synonyms, including Delta(6)-Desaturase, Delta-6 Fatty Acid Desaturase, Fatty Acid Delta-6-Desaturase, Linoleic Acid Delta-6 Desaturase, Linoleoyl CoA Desaturase, and Linoleoyl Coenzyme A Desaturase, all listed as entry terms in the [Medical Subject Headings](https://www.edgepedia.org/medical-subject-headings) (MeSH) vocabulary.[1](https://meshb.nlm.nih.gov/record/ui?dcmsLinks=true&ui=D050602) The MeSH descriptor was introduced on 1 January 2006, with a history note recording indexing under Fatty Acid Desaturases from 1981 to 2005.[1](https://meshb.nlm.nih.gov/record/ui?dcmsLinks=true&ui=D050602)
## References
1. [Linoleoyl-CoA Desaturase, MeSH Descriptor Data, National Library of Medicine](https://meshb.nlm.nih.gov/record/ui?dcmsLinks=true&ui=D050602)
2. [FADS2 - Acyl-CoA 6-desaturase - Homo sapiens, UniProtKB](https://www.uniprot.org/uniprotkb/O95864-3/entry)
3. [acyl-CoA 6-desaturase activity, GO:0016213, ZFIN](https://zfin.org/ZDB-TERM-091209-10155)
4. [acyl-CoA 6-desaturase, Creative Enzymes](https://www.creative-enzymes.com/downpdf.php?pid=11163)
5. [Fatty Acid Desaturases, MeSH, NCBI](https://www.ncbi.nlm.nih.gov/mesh?Cmd=DetailsSearch&Db=mesh&Term=%22Fatty+Acid+Desaturases%22%5BMeSH+Terms%5D)
6. [Delta-5 Fatty Acid Desaturase, MeSH Descriptor Data, National Library of Medicine](https://meshb.nlm.nih.gov/record/ui?dcmsLinks=true&ui=D000090943)
7. [An Evolutionary Perspective on Linoleic Acid Synthesis in Animals, PMC](https://pmc.ncbi.nlm.nih.gov/articles/PMC5816129/)
8. [Acyl Carriers Used as Substrates by the Desaturases and Elongases Involved in Very Long-chain Polyunsaturated Fatty Acids Biosynthesis Reconstituted in Yeast, ScienceDirect](https://www.sciencedirect.com/science/article/pii/S0021925820835674)
9. [Desaturases: Structural and mechanistic insights into the biosynthesis of unsaturated fatty acids, Wiley](https://onlinelibrary.wiley.com/doi/pdfdirect/10.1002/iub.2671)
10. [KEGG REACTION: R11043](https://www.kegg.jp/entry/R11043)
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*Topic: Encyclopedia › Life and health › Biological foundations › Biochemistry and metabolism › Metabolism and metabolic pathways › Lipid and fatty acid metabolism › Lipid metabolism enzyme families and activities › Desaturases, elongases, and fatty-acid modification enzymes*
*Initially written Sep 17, 2026 · Reviewed: Sep 30, 2026; Oct 21, 2026 · Edited: Sep 30, 2026; Oct 21, 2026 · Last review: Oct 21, 2026*
*Copyright 2026 EdgeChat AI, a subsidiary of Biostate AI.*
License: Edgepedia Community License 1.0, https://www.edgepedia.org/edgepedia/license