Omega-6 fatty acids and eicosanoids: the pathway in the body

This page shows the biochemical pathway behind the laboratory value Arachidonic acid, linoleic acid: which stations follow one another, which enzymes carry out each step and which cofactors they use. Every statement has a source. The page describes general textbook knowledge and says nothing about any individual person.

In brief

Omega-6 fatty acids such as linoleic acid and arachidonic acid are polyunsaturated fatty acids and building blocks of cell membranes. From released arachidonic acid, cells form eicosanoids, short-lived messengers such as prostaglandins and leukotrienes.

The pathway step by step

1. Linoleic acid → γ-Linolenic acid FADS2 (Δ6-desaturase) · NADH, Oxygen Delta-6 desaturase inserts a further double bond into the chain. The same enzyme also processes omega-3 fatty acids, so the two families compete for it. Source 1
2. γ-Linolenic acid → Dihomo-γ-linolenic acid ELOVL5 (elongase) An elongase adds two carbon atoms to the chain, forming dihomo-γ-linolenic acid. Source 1
3. Dihomo-γ-linolenic acid → Arachidonic acid FADS1 (Δ5-desaturase) · NADH, Oxygen Delta-5 desaturase inserts the fourth double bond, forming arachidonic acid. It also comes directly from animal foods. Source 1
4. Arachidonic acid → In the cell membrane Arachidonic acid is built into the phospholipids of cell membranes. Most of it stays there until a stimulus reaches the cell. Source 2
5. Free arachidonic acid → PGH₂ COX-1, COX-2 · Oxygen, Haem The cyclooxygenases COX-1 and COX-2 add oxygen and form a ring. PGH₂ is formed via the intermediate PGG₂. Source 3
6. Free arachidonic acid → LTA₄ 5-Lipoxygenase · FLAP, Calcium 5-lipoxygenase moves with calcium to the nuclear membrane and works there with the helper protein FLAP. LTA₄ is formed via the intermediate 5-HPETE. Source 4
7. PGH₂ → Prostaglandins Synthases Tissue-specific synthases turn PGH₂ into various prostaglandins. They break down quickly and therefore act only close to where they are made. Source 3
8. PGH₂ → Thromboxane A₂ Thromboxane synthase In platelets, thromboxane synthase converts PGH₂ into thromboxane A₂. It makes platelets stick together and vascular muscle contract. Source 3
9. LTA₄ → LTB₄ LTA₄ hydrolase LTA₄ hydrolase turns LTA₄ into leukotriene B₄. It acts as an attractant for white blood cells. Source 5
10. LTA₄ → Cysteinyl leukotrienes LTC₄ synthase · Glutathione LTC₄ synthase attaches glutathione to LTA₄. This gives rise in turn to LTC₄, LTD₄ and LTE₄, which act on smooth muscle and blood vessels. Source 4, 5
11. EPA → Eicosanoids from EPA COX, lipoxygenases When COX and lipoxygenases convert EPA, series-3 prostaglandins and series-5 leukotrienes are formed. They bind to the same receptors but act more weakly there. Source 6

Cofactors in this pathway

• Iron — Haem iron in the cyclooxygenases COX-1 and COX-2; non-haem iron in 5-lipoxygenase Source 3, 4In the ORY catalogue as a laboratory value: Eisen
• Calcium — Guides cPLA2 and 5-lipoxygenase to the membranes where arachidonic acid is released Source 2, 4In the ORY catalogue as a laboratory value: Calcium (intrazellulär)
• Glutathione — Attached to LTA₄ by LTC₄ synthase, forming the cysteinyl leukotrienes Source 4, 5In the ORY catalogue as a laboratory value: Glutathion (GSH)
• NADH — Electron donor for the desaturases FADS1 and FADS2, which insert double bonds Source 1

Sources

1. Brenna JT, Kothapalli KSD. New understandings of the pathway of long-chain polyunsaturated fatty acid biosynthesis. Curr Opin Clin Nutr Metab Care 2022 · PubMed 34937850
2. Leslie CC. Regulation of the specific release of arachidonic acid by cytosolic phospholipase A2. Prostaglandins Leukot Essent Fatty Acids 2004 · PubMed 15041029
3. Smith WL, DeWitt DL, Garavito RM. Cyclooxygenases: structural, cellular, and molecular biology. Annu Rev Biochem 2000 · PubMed 10966456
4. Peters-Golden M, Brock TG. 5-lipoxygenase and FLAP. Prostaglandins Leukot Essent Fatty Acids 2003 · PubMed 12895592
5. Wan M, Tang X, Stsiapanava A et al. Biosynthesis of leukotriene B4. Semin Immunol 2017 · PubMed 29042025
6. Calder PC. Marine omega-3 fatty acids and inflammatory processes: Effects, mechanisms and clinical relevance. Biochim Biophys Acta 2015 · PubMed 25149823

Related pathways

• Omega-3 fatty acids — epa
• Nitrosative stress — Eisen, Calcium (intrazellulär)
• 8-OHdG — Eisen, Glutathion (GSH)
• Calprotectin — Eisen, Calcium (intrazellulär)
• Copper — Eisen, Glutathion (GSH)

As of 2026-09-16. Draft written by Claude to schema v2; sources checked in PubMed; expert review pending
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