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Metabolic trap
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=== Kynurenine pathway=== [[File:IDO-MetabolicTrap-MECFS.png|thumb|right|'''An IDO metabolic trap in the kynurenine pathway may be the cause of ME/CFS.''' Colored rectangles represent molecules in either extracellular space or serotonergic neuron cytosol. Arrows represent processes including transport and biochemical reactions. LAT1 = large neutral amino acid transporter (SLC7A5:SLC3A2), IDO = indoleamine-2,3-dioxygenase, AFMID = arylforamidase, TPH = tryptophan hydroxylase, AADC = aromatic amino acid decarboxylase. ''Citation: [https://www.mdpi.com/2075-4418/9/3/82 Phair, Davis and Kashi (2019). Diagnostics (9)3. doi 10.3390/diagnostics9030082]'']] There is, as yet, little evidence for a strong role of the kyneruinine pathway in ME/CFS. Current research suggests involvement in the condition, but no more-so than would be expected based on the fact that the kyneurnine pathway has a wide variety of roles in inflammation, the immune response, and metabolism. As a result the metabolic trap hypothesis, while a valuable theory, should not be expected to have a great deal of explanatory power in the etiology of CFS *CFS/ME patients do appear to exhibit mild over-representation of loss of function mutations in IDO2 gene <ref name="WarrenTate2023">{{Cite web |last=Tate |first=Warren |date=25 May 2022 |title=Molecular Mechanisms of Neuroinflammation in ME/CFS and Long COVID to Sustain Disease and Promote Relapses |website=Frontiers in Neurology |url=https://www.frontiersin.org/journals/neurology/articles/10.3389/fneur.2022.877772/full?mibextid=ghrler&fs=e&s=cl |access-date=11 February 2023}}</ref> *The levels of KP metabolites in patients, while pointing to KP dysregulation, are not consistently correlated in the ways expected assuming a strong role for the metabolic trap in ME/CFS. Some studies do report higher TRP/KYN ratios in patients with CFS <ref name="Johnson2018">{{Cite web |last=Johnson |first=Cort |date=19 October 2018 |title=HealthRising: The Metabolic Trap Shines During the Symposium on the Molecular Basis of ME/CFS at Stanford |website=Open Medicine Foundation |url=https://www.omf.ngo/2018/10/19/healthrising-the-metabolic-trap-shines-during-the-symposium-on-the-molecular-basis-of-me-cfs-at-stanford/ |access-date=3 June 2019}}</ref>, while others report a lower KA/QA ratios, and a recent study showing higher levels of 3HK. Perhaps most relevantly, the finding in one study that there's no relationship between KP levels, cytokines and fatty acids <ref name="Kavyani2022">{{Cite web |last=Kavyani |first=Bahar |date=11 July 2022 |title=Could the kynurenine pathway be the key missing piece of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) complex puzzle? |website=PubMed Central (PMC) |url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9276562/ |access-date=11 February 2023}}</ref> *Computer simulation results showing the trap would be very difficult to escape, but would be sudden when it does occur. This is consistent with the real world observation that recovery from ME/CFS is rare, but sometimes happens very suddenly.
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