Kynurenine pathway

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

ME/CFS
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.

Notable studies

 * 1992, Quinolinic acid and kynurenine pathway metabolism in inflammatory and non-inflammatory neurological disease - (Full text)
 * 2004, Heterogeneity of serum tryptophan concentration and availability to the brain in patients with the chronic fatigue syndrome - (Full text)
 * 2014, Activation of the kynurenine pathway in the acute phase of stroke and its role in fatigue and depression following stroke - (Full text)
 * 2017, The Kynurenine Pathway As a Novel Link between Allergy and the Gut Microbiome - (Full text)
 * 2017, Kynurenines: Tryptophan's metabolites in exercise, inflammation, and mental health - (Abstract)
 * 2018, Tryptophan-Kynurenine Metabolites in Exercise and Mental Health - (Chapter)
 * 2019, The IDO Metabolic Trap Hypothesis for the Etiology of ME/CFS - (Full text)
 * 2021, Tryptophan Metabolites, Cytokines, and Fatty Acid Binding Protein 2 in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome - (Full text)
 * 2021, Increased Kynurenine Indicates a Fatal Course of COVID-19 - (Full text)

Learn more

 * What is the tryptophan kynurenine pathway and why is it important to neurotherapeutics? Davis and Liu (2015)
 * Indoleamine 2,3-Dioxygenase and Tolerance: Where Are We Now? - Mellor et al. (2017)