# Leukotriene
Leukotrienes (LTs) are lipid inflammatory mediators produced from arachidonic acid, a carbon-20 polyunsaturated fatty acid, through the 5-lipoxygenase (5-LO) pathway; they belong to the eicosanoid family, named from the Greek "eicosa" meaning 20.[1](https://onlinelibrary.wiley.com/doi/10.1155/2017/2432958) Two classes exist: the dihydroxy fatty acid leukotriene B4 (LTB4), a potent chemoattractant for leukocytes, and the cysteinyl leukotrienes (cysLTs) LTC4, LTD4, and LTE4, which are extremely potent bronchoconstrictors central to asthma and allergy.[2](https://www.annualreviews.org/doi/pdf/10.1146/annurev-pharmtox-051921-085014) • [3](https://www.annualreviews.org/content/journals/10.1146/annurev.med.52.1.1) The family was identified by [Bengt Samuelsson](https://www.edgepedia.org/bengt-samuelsson)'s laboratory at the Karolinska Institute, work recognized in the 1982 [Nobel Prize in Physiology or Medicine](https://www.edgepedia.org/nobel-prize-in-physiology-or-medicine).[4](https://www.nasonline.org/wp-content/uploads/2024/12/Samuelsson-Bengt.pdf)
| Key fact | Detail |
|---|---|
| Chemical origin | Arachidonic acid metabolized by the 5-lipoxygenase pathway; eicosanoids named for the 20-carbon fatty acid precursor[1](https://onlinelibrary.wiley.com/doi/10.1155/2017/2432958) |
| Two classes | LTB4 (dihydroxy fatty acid) and the cysteinyl leukotrienes LTC4, LTD4, and LTE4, formed by sequential peptidolytic cleavage[2](https://www.annualreviews.org/doi/pdf/10.1146/annurev-pharmtox-051921-085014) |
| Central enzyme | 5-LO converts arachidonic acid to LTA4 in two steps, supported by the accessory proteins FLAP and coactosin-like protein[5](https://pubmed.ncbi.nlm.nih.gov/10591081/) • [2](https://www.annualreviews.org/doi/pdf/10.1146/annurev-pharmtox-051921-085014) |
| Receptors | Seven-transmembrane G-protein-coupled receptors: BLT1 and BLT2 (high- and low-affinity LTB4 receptors) and CysLT1R and CysLT2R for the cysLTs[1](https://onlinelibrary.wiley.com/doi/10.1155/2017/2432958) |
| Discovery | Unveiled as a new family of lipid mediators by Samuelsson in 1979; identified as the basis of slow-reacting substance of anaphylaxis (SRS-A)[4](https://www.nasonline.org/wp-content/uploads/2024/12/Samuelsson-Bengt.pdf) |
| Clinical use | Leukotriene synthesis inhibitors and receptor antagonists are FDA-approved drugs for asthma, such as montelukast[3](https://www.annualreviews.org/content/journals/10.1146/annurev.med.52.1.1) • [4](https://www.nasonline.org/wp-content/uploads/2024/12/Samuelsson-Bengt.pdf) |
## Biosynthesis
Leukotriene synthesis begins with cleavage of arachidonic acid from glycerophospholipids of the cellular nuclear membrane, catalyzed by cytosolic phospholipase A2.[1](https://onlinelibrary.wiley.com/doi/10.1155/2017/2432958) • [6](https://www.frontiersin.org/articles/10.3389/fimmu.2013.00130/pdf) The enzyme 5-lipoxygenase then carries out a two-step conversion: oxidation of arachidonic acid to the unstable intermediate 5-hydroperoxyeicosatetraenoic acid (5-HPETE), followed by dehydration to form leukotriene A4 (LTA4), a highly reactive epoxide.[5](https://pubmed.ncbi.nlm.nih.gov/10591081/) These are the first committed reactions leading to all leukotrienes and play a critical role in controlling their production.[5](https://pubmed.ncbi.nlm.nih.gov/10591081/)
**Branch point.** LTA4 is the pivot of the pathway. LTA4 hydrolase converts it to LTB4, while LTC4 synthase conjugates it with glutathione to form LTC4, the parent compound of the cysteinyl leukotrienes.[7](https://pubmed.ncbi.nlm.nih.gov/17623009/) LTC4 is converted to LTD4 and finally to LTE4 after extracellular transport, by sequential peptidolytic cleavage.[3](https://www.annualreviews.org/content/journals/10.1146/annurev.med.52.1.1) • [2](https://www.annualreviews.org/doi/pdf/10.1146/annurev-pharmtox-051921-085014) Full biosynthetic capacity from arachidonic acid is largely confined to leukocytes, and production requires cellular activation, such as IgE receptor cross-binding on mast cells; the accessory protein FLAP binds 5-LO and facilitates arachidonic acid metabolism, and coactosin-like protein (CLP) provides additional support.[8](https://www.sciencedirect.com/science/article/pii/S095232780300070X) • [9](https://pmc.ncbi.nlm.nih.gov/articles/PMC4033953/) • [2](https://www.annualreviews.org/doi/pdf/10.1146/annurev-pharmtox-051921-085014)
## Receptors and signaling
Leukotrienes act through specific seven-transmembrane G-protein-coupled cell surface receptors.[1](https://onlinelibrary.wiley.com/doi/10.1155/2017/2432958) LTB4 signals through BLT1, the high-affinity receptor, and BLT2, the low-affinity receptor; the cysteinyl leukotrienes activate CysLT1R and CysLT2R, and an LTE4-specific receptor (CysLT_ER) has been identified in mice lacking both CysLT1R and CysLT2R.[1](https://onlinelibrary.wiley.com/doi/10.1155/2017/2432958) Receptor expression is broad across cell types, and the receptors BLT1 and DP2 (CRTH2, a prostaglandin D2 receptor) are highly expressed and functional on specific T-cell subsets.[10](https://www.nature.com/articles/nri1438)
## Role in inflammation
Pro-inflammatory prostaglandins and LTB4 control local blood flow, vascular dilation, and permeability changes needed for leukocyte adhesion, diapedesis, and recruitment at an inflammatory site.[11](https://pmc.ncbi.nlm.nih.gov/articles/PMC2739396/) LTB4 is a potent mediator of leukocyte function and chemoattractant activity.[12](https://www.sciencedirect.com/science/article/pii/0002934386900732) Generation of BLT1-deficient mice revealed a role for LTB4 in T-cell trafficking early in allergic pulmonary inflammation.[10](https://www.nature.com/articles/nri1438) Leukotrienes are also involved in immunomodulation and in the genesis of atherosclerosis.[13](https://pmc.ncbi.nlm.nih.gov/articles/PMC10253712/)
**Mediator switching.** As inflammation proceeds, neutrophils within contained exudates stop producing chemoattractants such as LTB4 and, within hours, begin converting arachidonic acid into lipoxins, protective mediators that actively terminate inflammation and promote resolution.[14](https://pmc.ncbi.nlm.nih.gov/articles/PMC2744593/) During complete resolution, mediator switching also occurs between families, from eicosanoids to resolvins of the E and D series and protectins.[11](https://pmc.ncbi.nlm.nih.gov/articles/PMC2739396/)
## Leukotrienes in asthma
The cysteinyl leukotrienes are extremely potent bronchoconstricting agents that are pathogenetic in both asthma and allergy; they occupy the same receptors and are also reported to be chemotactic for eosinophils.[3](https://www.annualreviews.org/content/journals/10.1146/annurev.med.52.1.1) In asthma and chronic obstructive pulmonary disease, excess leukotriene production contributes to bronchoconstriction and mucosal edema.[15](https://onlinelibrary.wiley.com/doi/full/10.1111/imcb.70076) The cysteinyl leukotrienes LTC4, LTD4, and LTE4 together constitute the biological activity long known as slow-reacting substance of anaphylaxis (SRS-A), a powerful bronchoconstrictor generated during anaphylactic shock that was discovered in 1938 by the Australian medical researcher Charles H. Kellaway and co-workers.[4](https://www.nasonline.org/wp-content/uploads/2024/12/Samuelsson-Bengt.pdf)
## Therapeutic targeting
Antileukotriene therapies work in two ways: inhibiting leukotriene synthesis through 5-lipoxygenase inhibition, or blocking the cysLT receptor.[3](https://www.annualreviews.org/content/journals/10.1146/annurev.med.52.1.1) These drugs are approved by the US Food and Drug Administration for asthma; they are moderately efficacious in general but highly efficacious in aspirin-induced asthma, and they are additive to inhaled corticosteroids and beta-adrenoceptor agonists, so they are frequently used as supplemental treatment when asthma is not controlled by other drugs.[3](https://www.annualreviews.org/content/journals/10.1146/annurev.med.52.1.1) [Montelukast](https://www.edgepedia.org/montelukast), a leukotriene receptor antagonist, is not as effective as long-acting beta agonists when added to inhaled corticosteroid therapy in preventing exacerbations in moderate asthma, but addition of a leukotriene receptor antagonist or synthesis inhibitor has shown some efficacy on lung function in adults with moderate-to-severe asthma not taking LABAs.[16](https://publications.ersnet.org/content/erj/43/2/343) Leukotriene synthesis inhibitors and receptor antagonists have been shown to modulate features of asthma and allergic diseases more broadly.[17](https://onlinelibrary.wiley.com/doi/10.1111/all.14295)
**Interaction with NSAIDs.** Many nonsteroidal anti-inflammatory drugs increase formation of slow-reacting substance after allergen challenge, perhaps by inhibiting cyclooxygenase and thereby releasing more arachidonic acid for metabolism by lipoxygenase pathways.[12](https://www.sciencedirect.com/science/article/pii/0002934386900732)
## Discovery history
The pathway emerged from Samuelsson's broader work on arachidonic acid metabolism, for which he shared the 1982 Nobel Prize in Physiology or Medicine with [Sune K. Bergström](https://www.edgepedia.org/sune-k-bergstrom) and [John R. Vane](https://www.edgepedia.org/john-r-vane) for discoveries concerning prostaglandins and related biologically active substances.[18](https://www.livescience.com/16342-nobel-prize-medicine-history-list.html) A 5-lipoxygenase was discovered in 1976, and in that year Borgeat, Hamberg, and Samuelsson reported that arachidonic acid was metabolized by the 5-lipoxygenase pathway.[4](https://www.nasonline.org/wp-content/uploads/2024/12/Samuelsson-Bengt.pdf) • [19](https://www.jacionline.org/article/S0091674906017696/pdf) In 1979, at the second International Conference on Prostaglandins and Related Compounds in Washington, DC, Samuelsson unveiled the leukotrienes as a completely new family of lipid mediators, and his group reported the pivotal role of the epoxide intermediate LTA4, linking the 5-lipoxygenase pathway to the structural elucidation of SRS-A.[4](https://www.nasonline.org/wp-content/uploads/2024/12/Samuelsson-Bengt.pdf) • [19](https://www.jacionline.org/article/S0091674906017696/pdf) Samuelsson, Robert Murphy, and Sven Hammarström confirmed that SRS-A is a glutathione conjugate of LTA4, named LTC4, and subsequent research showed its conversion to LTD4 and LTE4.[4](https://www.nasonline.org/wp-content/uploads/2024/12/Samuelsson-Bengt.pdf) Samuelsson's discovery of the leukotrienes led to medicines used against asthma.[20](https://ki.se/om-ki/priser-och-hogtider/priser-och-utmarkelser/nobelpriset-i-fysiologi-eller-medicin/sune-bergstrom-och-bengt-samuelsson-fann-mekanismerna-bakom-karlsjukdom)
## References
1. [Role of the Cysteinyl Leukotrienes in the Pathogenesis and Progression of Cardiovascular Diseases, Mediators of Inflammation (2017)](https://onlinelibrary.wiley.com/doi/10.1155/2017/2432958)
2. [Structures of Leukotriene Biosynthetic Enzymes and Development of New Therapeutics, Annual Review of Pharmacology and Toxicology](https://www.annualreviews.org/doi/pdf/10.1146/annurev-pharmtox-051921-085014)
3. [Regulation of Leukotrienes in the Management of Asthma: Biology and Clinical Therapy, Annual Review of Medicine 52:1-14 (2001)](https://www.annualreviews.org/content/journals/10.1146/annurev.med.52.1.1)
4. [Bengt I. Samuelsson (1934-2024), National Academy of Sciences Biographical Memoir](https://www.nasonline.org/wp-content/uploads/2024/12/Samuelsson-Bengt.pdf)
5. [The biology of 5-lipoxygenase: function, structure, and regulatory mechanisms, Proc Assoc Am Physicians (1999)](https://pubmed.ncbi.nlm.nih.gov/10591081/)
6. [Proinflammatory and immunoregulatory roles of eicosanoids in T cells, Frontiers in Immunology (2013)](https://www.frontiersin.org/articles/10.3389/fimmu.2013.00130/pdf)
7. [Biosynthesis and metabolism of leukotrienes, Biochemical Journal 405:379-95 (2007)](https://pubmed.ncbi.nlm.nih.gov/17623009/)
8. [5-Lipoxygenase and FLAP, Prostaglandins, Leukotrienes and Essential Fatty Acids 69:99-109 (2003)](https://www.sciencedirect.com/science/article/pii/S095232780300070X)
9. [Role of Leukotrienes and Leukotriene Modifiers in Asthma, PMC](https://pmc.ncbi.nlm.nih.gov/articles/PMC4033953/)
10. [T-cell trafficking in asthma: lipid mediators grease the way, Nature Reviews Immunology 4:711-724 (2004)](https://www.nature.com/articles/nri1438)
11. [Anti-Inflammatory and Pro-Resolving Lipid Mediators, PMC](https://pmc.ncbi.nlm.nih.gov/articles/PMC2739396/)
12. [Prostaglandins, thromboxanes, and leukotrienes in inflammation, ScienceDirect](https://www.sciencedirect.com/science/article/pii/0002934386900732)
13. [Pro- and Anti-Inflammatory Prostaglandins and Cytokines in Humans: A Mini Review, PMC](https://pmc.ncbi.nlm.nih.gov/articles/PMC10253712/)
14. [Resolving inflammation: dual anti-inflammatory and pro-resolution lipid mediators, PMC](https://pmc.ncbi.nlm.nih.gov/articles/PMC2744593/)
15. [Unpacking the lipid-immune axis in health and disease, Immunology & Cell Biology (2026)](https://onlinelibrary.wiley.com/doi/full/10.1111/imcb.70076)
16. [International ERS/ATS guidelines on definition, evaluation and treatment of severe asthma, European Respiratory Journal 43:343](https://publications.ersnet.org/content/erj/43/2/343)
17. [Current perspective on eicosanoids in asthma and allergic diseases: EAACI Task Force consensus report, part I, Allergy (2021)](https://onlinelibrary.wiley.com/doi/10.1111/all.14295)
18. [Nobel Prize in Medicine: 1901-Present, Live Science](https://www.livescience.com/16342-nobel-prize-medicine-history-list.html)
19. [History of leukotriene discovery, Journal of Allergy and Clinical Immunology (2006)](https://www.jacionline.org/article/S0091674906017696/pdf)
20. [Sune Bergström och Bengt Samuelsson fann mekanismerna bakom kärlsjukdom, Karolinska Institutet](https://ki.se/om-ki/priser-och-hogtider/priser-och-utmarkelser/nobelpriset-i-fysiologi-eller-medicin/sune-bergstrom-och-bengt-samuelsson-fann-mekanismerna-bakom-karlsjukdom)
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*Topic: Encyclopedia › Life and health › Biological foundations › Biochemistry and metabolism › Metabolites, cofactors, and biomolecules › Metabolite records › Human metabolites › Endogenous lipid metabolites*
*Initially written Sep 17, 2026 · Reviewed: Oct 21, 2026 · Edited: Oct 15, 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