Kynurenine pathway

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Kynurenine pathway
Source: Mellor AL, Lemos H and Huang L (2017). Front. Immunol.8:1360.

The kynurenine pathway or tryptophan kynurenine pathway is the primary route for metabolizing the essential amino acid tryptophan in humans and other mammals[1] in order to generate cellular energy in the form of nicotinamide adenine dinucleotide (NAD+).[2][3]

If the kynurenine pathway becomes dysregulated or overactive, it can activate the immune system and result in a build-up of potentially neurotoxic compounds in the body.[3]

Function[edit | edit source]

Schematic representation of the kynurenine pathway.
Key: IDO1: indoleamine 2,3-dioxygenase 1; IDO2: indoleamine 2,3-dioxygenase 2; TDO2: tryptophan 2,3-dioxygenase; TPH1: Tryptophan hydroxylase 1; TPH2: Tryptophan hydroxylase 2; AFMID: arylformamidase; KMO: kynurenine 3-monooxygenase; CCBL1: kynurenine aminotransferase I; AADAT: kynurenine aminotransferase II; CCBL2: kynurenine aminotransferase III; KYNU: kynureninase; HAAO: 3-hydroxyanthranilate 3,4-dioxygenase; QPRT, quinolinate phosphoribosyl transferase; ACMSD: aminocarboxymuconate semialdehyde decarboxylase. Source: Favennec et al. (2016). PLoS ONE 11(6): e0158051

ME/CFS[edit | edit source]

The metabolic trap hypothesis suggests that a metabolic problem exists in one or more areas of a person with ME/CFS, with a defect in the IDO2 enzyme of the tryptophan kynurenine pathway being identified as a possible metabolic trap.

In May 2020, the Open Medicine Foundation announced a pilot treatment trial of kynurenine for ME/CFS patients.[4]

See also
Metabolic trap.

Notable studies[edit | edit source]

  • 1992, Quinolinic acid and kynurenine pathway metabolism in inflammatory and non-inflammatory neurological disease[5] - (Full text)
  • 2004, Heterogeneity of serum tryptophan concentration and availability to the brain in patients with the chronic fatigue syndrome[6] - (Full text)
  • 2014, Activation of the kynurenine pathway in the acute phase of stroke and its role in fatigue and depression following stroke[7] - (Full text)
  • 2017, The Kynurenine Pathway As a Novel Link between Allergy and the Gut Microbiome[8] - (Full text)
  • 2019, The IDO Metabolic Trap Hypothesis for the Etiology of ME/CFS[9] - (Full text)

See also[edit | edit source]

Learn more[edit | edit source]

References[edit | edit source]

  1. ↑ Chen, Yiquan; Guillemin, Gilles J. (January 8, 2009). "Kynurenine Pathway Metabolites in Humans: Disease and Healthy States". International Journal of Tryptophan Research : IJTR. 2: 1–19. ISSN 1178-6469. PMC 3195227. PMID 22084578.
  2. ↑ Savitz, Jonathan (April 12, 2019). "The kynurenine pathway: a finger in every pie". Molecular Psychiatry: 1–17. doi:10.1038/s41380-019-0414-4. ISSN 1476-5578.
  3. ↑ 3.0 3.1 3.2 Davis, I.; Liu, A. (July 2015). "What is the tryptophan kynurenine pathway and why is it important to neurotherapeutics?". Expert review of neurotherapeutics. 15 (7): 719–721. doi:10.1586/14737175.2015.1049999. ISSN 1473-7175. PMID 26004930.
  4. ↑ Open Medicine Foundation. "#May Momentum 2020". Open Medicine Foundation. Retrieved May 1, 2020. Cite has empty unknown parameter: |dead-url= (help)
  5. ↑ Heyes, M. P.; Saito, K.; Crowley, J. S.; Davis, L. E.; Demitrack, M. A.; Der, M.; Dilling, L. A.; Elia, J.; Kruesi, M. J. (October 1992). "Quinolinic acid and kynurenine pathway metabolism in inflammatory and non-inflammatory neurological disease" (PDF). Brain: A Journal of Neurology. 115 ( Pt 5): 1249–1273. doi:10.1093/brain/115.5.1249. ISSN 0006-8950. PMID 1422788.
  6. ↑ Badawy, Abdulla A.-B.; Morgan, Christopher J.; Llewelyn, Meirion B.; Albuquerque, Selwyn R. J.; Farmer, Anne (July 2005). "Heterogeneity of serum tryptophan concentration and availability to the brain in patients with the chronic fatigue syndrome". Journal of Psychopharmacology (Oxford, England). 19 (4): 385–391. doi:10.1177/0269881105053293. ISSN 0269-8811. PMID 15982993.
  7. ↑ Ormstad, Heidi; Verkerk, Robert; Amthor, Karl-Friedrich; Sandvik, Leiv (2014). "Activation of the kynurenine pathway in the acute phase of stroke and its role in fatigue and depression following stroke" (PDF). Journal of molecular neuroscience: MN. 54 (2): 181–187. doi:10.1007/s12031-014-0272-0. ISSN 1559-1166. PMID 24664436.
  8. ↑ Van der Leek, Aaron P.; Yanishevsky, Yarden; Kozyrskyj, Anita L. (2017). "The Kynurenine Pathway As a Novel Link between Allergy and the Gut Microbiome". Frontiers in Immunology. 8: 1374. doi:10.3389/fimmu.2017.01374. ISSN 1664-3224. PMC 5681735. PMID 29163472.
  9. ↑ Phair, Robert D.; Davis, Ronald W.; Kashi, Alex A. (2019). "The IDO Metabolic Trap Hypothesis for the Etiology of ME/CFS". Diagnostics. 9 (3): 82. doi:10.3390/diagnostics9030082.
  10. ↑ Mellor, Andrew L.; Lemos, Henrique; Huang, Lei (2017). "Indoleamine 2,3-Dioxygenase and Tolerance: Where Are We Now?". Frontiers in Immunology. 8. doi:10.3389/fimmu.2017.01360. ISSN 1664-3224.

indoleamine (IDO) - any derivatives of an indole (e.g., serotonin, tryptophan) that contain an amine group

enzyme a substance produced by a living organism which acts as a catalyst to bring about a specific biochemical reaction.

metabolic trap hypothesis An hypothesis which proposes that the normal metabolic functioning of the cell has become "trapped" in an abnormal state, which may lead to body-wide symptoms.

serum The clear yellowish fluid that remains from blood plasma after clotting factors have been removed by clot formation. (Blood plasma is simply blood that has had its blood cells removed.)

microbiome The full collection of microscopic organisms (especially bacteria and fungi) which are present in a particular environment, particularly inside the human body.

indoleamine (IDO) - any derivatives of an indole (e.g., serotonin, tryptophan) that contain an amine group

indole (IDO) - a signalling molecule produced by bacteria as a result of metabolising tryptophan, found in the intestines

metabolic trap hypothesis An hypothesis which proposes that the normal metabolic functioning of the cell has become "trapped" in an abnormal state, which may lead to body-wide symptoms.

etiology The cause of origin, especially of a disease.

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