Kynurenine pathway

From MEpedia, a crowd-sourced encyclopedia of ME and CFS science and history
Jump to: navigation, search

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]

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. (Jan 8, 2009). "Kynurenine Pathway Metabolites in Humans: Disease and Healthy States". International Journal of Tryptophan Research : IJTR. 2: 1–19. ISSN 1178-6469. PMC 3195227Freely accessible. PMID 22084578. 
  2. Savitz, Jonathan (Apr 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. 3.03.13.2 Davis, I.; Liu, A. (Jul 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. 
  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. (Oct 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 (Jul 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 5681735Freely accessible. 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. 

ME/CFS - An acronym that combines myalgic encephalomyelitis with chronic fatigue syndrome. Sometimes they are combined because people have trouble distinguishing one from the other. Sometimes they are combined because people see them as synonyms of each other.

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.)

chronic fatigue syndrome (CFS) - A fatigue-based illness. The term CFS was invented invented by the U.S. Centers for Disease Control as an replacement for myalgic encephalomyelitis (ME). Some view CFS as a neurological disease, others use the term for any unexplained long-term fatigue. Sometimes used as a the term as a synonym of myalgic encephalomyelitis, despite the different diagnostic criteria.

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

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.

The information provided at this site is not intended to diagnose or treat any illness.
From MEpedia, a crowd-sourced encyclopedia of ME and CFS science and history.