Omega-3 fatty acids: the pathway in the body · Biomarker & Blood Analysis

This page shows the biochemical pathway behind the laboratory value Omega-3 fatty acids: ALA, EPA, DHA: 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-3 fatty acids such as ALA, EPA and DHA are polyunsaturated fatty acids whose first double bond lies at the third carbon from the end of the chain. The body builds them into cell membranes and forms messengers such as resolvins from EPA and DHA. EPA rivals arachidonic acid.

The pathway step by step

Each station states what the compound does there. Three signs: ↑ supplies — builds up or makes available · ↓ depletes — inhibits, consumes or withholds · ↕ both, depending on amount. Behind it stands what the statement rests on: established physiology, observed in studies, or contested. The signs do not grade; they name the direction.

1. ALA → Stearidonic acid FADS2 (Δ6-desaturase) · NADH, cytochrome b5 Δ6-desaturase (FADS2) inserts another double bond. The same enzyme also processes omega-6 fatty acids, which compete with the omega-3 fatty acids for access to it. This step is regarded as the slowest of the route. Source 1, 2↑ supplies The step through Δ6-desaturase is regarded as the slowest of the route. It determines how much ALA moves on towards EPA at all; linoleic acid from the omega-6 series occupies the same enzyme. established physiology Source 1, 2
   ⚖ When the balance tips

   too much — If a lot of substrate arrives at once, ALA and linoleic acid, both compete for Δ6-desaturase. The more linoleic acid there is, the less ALA is converted to stearidonic acid.

   too little — If little stearidonic acid forms, because Δ6-desaturase works slowly or is occupied by omega-6 fatty acids, little EPA arrives further down the route as well.

   established physiology · Source 1

2. Stearidonic acid → Eicosatetraenoic acid ELOVL5 (elongase) · Malonyl-CoA, NADPH An elongase (ELOVL5) adds two carbon atoms; malonyl-CoA supplies the building block and NADPH the electrons. This forms the direct precursor of EPA. Source 2↑ supplies The elongation uses up malonyl-CoA and NADPH and supplies the chain with twenty carbon atoms that Δ5-desaturase converts to EPA. established physiology Source 2
   ⚖ When the balance tips

   too much — If eicosatetraenoic acid builds up, the following Δ5-desaturase sets how much of it becomes EPA.

   too little — If little malonyl-CoA or NADPH is available, the elongase cannot keep up, and less precursor for EPA forms.

   established physiology · Source 2

3. Eicosatetraenoic acid → EPA FADS1 (Δ5-desaturase) · NADH, cytochrome b5 Δ5-desaturase (FADS1) inserts the fifth double bond. EPA has twenty carbon atoms and is the starting material for its own group of messengers. Once released, EPA competes with arachidonic acid for cyclooxygenases and lipoxygenases. Source 1, 3↕ both, depending on amount Once released from the membrane, EPA competes with arachidonic acid for cyclooxygenases and lipoxygenases. It supplies its own 3-series messengers and precursors of E-series resolvins and withdraws enzyme sites from arachidonic acid. established physiology Source 3
   ⚖ When the balance tips

   too much — If there is a lot of EPA in the membranes, less thromboxane A2 forms from arachidonic acid; the thromboxane A3 formed instead acts more weakly on platelets, and clotting runs slightly delayed.

   too little — If little EPA is available, cyclooxygenases and lipoxygenases mainly convert arachidonic acid, and little 18-HEPE forms as the precursor of E-series resolvins.

   observed in studies · Source 3

4. EPA → DPA ELOVL2 (elongase) · Malonyl-CoA, NADPH The elongase ELOVL2 lengthens EPA by two further carbon atoms. DPA is the precursor for the body's own DHA formation. Source 2↑ supplies DPA is the precursor from which DHA forms through further elongation, desaturation and shortening in the peroxisome. ELOVL2 also carries out the next elongation step. established physiology Source 2
   ⚖ When the balance tips

   too much — If more precursor arrives, DPA rises with it, but DHA hardly does: the following steps up to shortening in the peroxisome limit the flow.

   too little — If little DPA is available, the body's own DHA formation has hardly any starting material; DHA then comes from food.

   established physiology · Source 1, 2

5. DPA → DHA ELOVL2, FADS2 · Peroxisomal shortening To form DHA, the chain is first lengthened and desaturated further; in the peroxisome a breakdown step then shortens it again by two carbon atoms. In humans this route runs only to a small extent. It sits mainly in the brain and retina. Source 2, 1↑ supplies DHA is the end product of the route. It is built preferentially into the membrane phospholipids of the brain, retina and sperm, where it makes up a large share of the fatty acids. established physiology Source 4, 2
   ⚖ When the balance tips

   too much — If a lot of DHA arrives, more of it is built into membrane phospholipids. With its six double bonds it oxidises easily; vitamin E scavenges the peroxyl radicals that form in the process.

   too little — If little DHA is available, the incorporating enzymes build in other polyunsaturated fatty acids in its place, above all an omega-6 fatty acid with 22 carbon atoms.

   observed in studies · Source 4, 9

6. 18-HEPE → E-series resolvins 5-lipoxygenase 5-lipoxygenase converts 18-HEPE further. The resulting resolvins bind to dedicated receptors on immune cells and are among the substances the body uses to end an inflammatory response. They slow the influx of further immune cells. Source 5, 3↓ depletes Resolvin E1 binds to the receptors ChemR23 and BLT1. It slows the influx of neutrophil granulocytes and prompts macrophages to engulf dead cells; in this way the inflammatory response subsides. observed in studies Source 5
   ⚖ When the balance tips

   too much — If many E-series resolvins are present, fewer neutrophil granulocytes migrate into the tissue in animal models, and the inflammatory response subsides sooner.

   too little — If few E-series resolvins are present, the influx of neutrophil granulocytes lasts longer in animal models, and the resolution of inflammation takes longer.

   observed in studies · Source 5

7. In membrane lipids → Resolvins, protectins 15-LOX, 5-LOX · Phospholipase A2 Phospholipase A2 releases DHA again. A 15-lipoxygenase converts it into 17-HpDHA, from which D-series resolvins, protectins and maresins are formed. These substances act as an inflammatory response subsides. Source 5, 3↓ depletes D-series resolvins, protectins and maresins slow the migration of neutrophil granulocytes and prompt macrophages to engulf dead cells and microbes. Maresins are also involved in tissue regeneration. observed in studies Source 5
   ⚖ When the balance tips

   too much — If many of these messengers are present, an inflammatory response subsides sooner in animal models, and macrophages clear the tissue faster.

   too little — If little DHA is released, little 17-HpDHA forms; in animal models the resolution of inflammation then takes longer.

   observed in studies · Source 5

Further stations

• ALA — Alpha-linolenic acid ALA is the plant omega-3 fatty acid from linseed, rapeseed and walnut. The body cannot make it itself; it has three double bonds and 18 carbon atoms. Only a small part of it is converted to EPA via desaturases and elongases. Source 1↑ supplies ALA is the starting material of the whole route. A large part is broken down in the mitochondria for energy; only a small part passes through desaturases and elongases as far as EPA. established physiology Source 1
  ⚖ When the balance tips

  too much — If more ALA arrives, a large part of it is broken down or stored. EPA and DPA rise only to a small extent with it, DHA hardly at all.

  too little — If little ALA is available, the body's own route has hardly any starting material; EPA and DHA then come almost entirely from food.

  established physiology · Source 1

• 18-HEPE — from released EPA When EPA is released from the membrane, cytochrome P450 enzymes or a modified cyclooxygenase-2 attach oxygen, forming 18-HEPE. 18-HEPE is the precursor of the E-series resolvins. Source 5, 3↑ supplies 18-HEPE is the precursor of the E-series resolvins. The route via the modified cyclooxygenase-2 arises when acetylsalicylic acid has acetylated the enzyme; the route via cytochrome P450 runs without it. established physiology Source 5, 3
  ⚖ When the balance tips

  too much — If a lot of 18-HEPE is present, 5-lipoxygenase in immune cells converts more of it to resolvin E1 and E2.

  too little — If little released EPA is available, little 18-HEPE forms, and the formation of E-series resolvins stalls at the very start.

  observed in studies · Source 5

• In membrane lipids — Phospholipids of membranes Dedicated enzymes build EPA and DHA into the phospholipids of cell membranes, mostly at the middle position of the glycerol backbone. There they change how flexible the membrane is. At the same time they form a store for messengers. Source 4↑ supplies In the membrane, EPA and DHA make the lipid layer more flexible and change how proteins in it work. At the same time they form the store from which phospholipase A2 releases them when needed. established physiology Source 4, 8
  ⚖ When the balance tips

  too much — If there is a lot of EPA and DHA in the membranes, they displace part of the arachidonic acid there; on release, more omega-3 fatty acids are then available to cyclooxygenases and lipoxygenases.

  too little — If little EPA and DHA is built in, omega-6 fatty acids such as arachidonic acid occupy their place, and on release mainly arachidonic acid messengers form.

  established physiology · Source 3, 4

Cofactors in this pathway

• Niacin (NADH, NADPH) — NADH supplies the electrons for the desaturases, NADPH for the elongases; without them the conversion of ALA stalls Source 2In the ORY catalogue as a laboratory value: NAD⁺ (Nicotinamidadenindinukleotid)
• Iron — Metal centre of the lipoxygenases that form resolvins from EPA and DHA; without iron they do not work Source 6In the ORY catalogue as a laboratory value: Eisen
• Biotin — Cofactor of acetyl-CoA carboxylase, which forms the malonyl-CoA for the elongases; without malonyl-CoA, no elongation Source 7
• Pantothenic acid (coenzyme A) — Building block of coenzyme A in malonyl-CoA and in activated fatty acids; only activated fatty acids are converted Source 2
• Calcium — A rise inside the cell activates cytosolic phospholipase A2, which releases fatty acids, preferentially arachidonic acid Source 8In the ORY catalogue as a laboratory value: Calcium (intrazellulär)
• Vitamin E — Scavenges peroxyl radicals in membranes containing polyunsaturated fatty acids and so limits their oxidation Source 9In the ORY catalogue as a laboratory value: Vitamin E (Tocopherol)

Sources

1. Burdge GC, Calder PC. Metabolism of alpha-linolenic acid in humans. Prostaglandins Leukot Essent Fatty Acids 2006 · PubMed 16828546
2. Qiu X. Biosynthesis of docosahexaenoic acid (DHA, 22:6-4, 7,10,13,16,19): two distinct pathways. Prostaglandins Leukot Essent Fatty Acids 2003 · PubMed 12538082
3. Dyall SC, Balas L, Bazan NG et al. Polyunsaturated fatty acids and fatty acid-derived lipid mediators: Recent advances in the understanding of their biosynthesis, structures, and functions. Prog Lipid Res 2022 · PubMed 35508275
4. Hishikawa D, Valentine WJ, Iizuka-Hishikawa Y et al. Metabolism and functions of docosahexaenoic acid-containing membrane glycerophospholipids. FEBS Lett 2017 · PubMed 28833063
5. Chiang N, Serhan CN. Specialized pro-resolving mediator network: an update on production and actions. Essays Biochem 2020 · PubMed 32885825
6. Wood I, Trostchansky A, Rubbo H. Structural considerations on lipoxygenase function, inhibition and crosstalk with nitric oxide pathways. Biochimie 2020 · PubMed 32980463
7. Tong L. Striking Diversity in Holoenzyme Architecture and Extensive Conformational Variability in Biotin-Dependent Carboxylases. Adv Protein Chem Struct Biol 2017 · PubMed 28683917
8. Leslie CC. Cytosolic phospholipase A2: physiological function and role in disease. J Lipid Res 2015 · PubMed 25838312
9. Traber MG, Atkinson J. Vitamin E, antioxidant and nothing more. Free Radic Biol Med 2007 · PubMed 17561088

Related pathways

• Omega-6 fatty acids and eicosanoids — epa
• Calprotectin — Eisen, Calcium (intrazellulär)
• Carnitine — NAD⁺ (Nicotinamidadenindinukleotid), Eisen
• Citric acid cycle — NAD⁺ (Nicotinamidadenindinukleotid), Eisen
• Coenzyme Q10 — NAD⁺ (Nicotinamidadenindinukleotid), Vitamin E (Tocopherol)

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