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, Kynurenines: Tryptophan's metabolites in exercise, inflammation, and mental health - (Abstract)
 * 2017, The Kynurenine Pathway As a Novel Link between Allergy and the Gut Microbiome - (Full text)
 * 2018, Tryptophan-Kynurenine Metabolites in Exercise and Mental Health - (Chapter)
 * 2019, The IDO Metabolic Trap Hypothesis for the Etiology of ME/CFS - (Full text)
 * 2019, The plasma [kynurenine]/[tryptophan] ratio and indoleamine 2, 3-dioxygenase: time for appraisal - (Full text)


 * 2020, Accumulation of kynurenine elevates oxidative stress and alters microRNA profile in human bone marrow stromal cells - (Full text)
 * 2020, Chronic fatigue and depression due to multiple sclerosis: Immune-inflammatory pathways, tryptophan catabolites and the gut-brain axis as possible shared pathways - (Full text)
 * 2020, IDO and kynurenine metabolites in peripheral and CNS disorders - (Full text)
 * 2020, The kynurenine pathway: a finger in every pie - (Full text)
 * 2021, A map of metabolic phenotypes in patients with myalgic encephalomyelitis/chronic fatigue syndrome - (Full text)
 * 2021, Co-players in chronic pain: Neuroinflammation and the tryptophan-kynurenine metabolic pathway - (Full text)
 * 2021, Kynurenine Metabolites and Ratios Differ Between Chronic Fatigue Syndrome, Fibromyalgia, and Healthy Controls - (Full text)
 * 2021, Kynurenine Pathway of Tryptophan Metabolism in Migraine and Functional Gastrointestinal Disorders - (Full text)
 * 2021, Incomplete Systemic Recovery and Metabolic Phenoreversion in Post-Acute-Phase Nonhospitalized COVID-19 Patients: Implications for Assessment of Post-Acute COVID-19 Syndrome - (Full text)
 * 2021, Increased Kynurenine Indicates a Fatal Course of COVID-19 - (Full text)
 * 2021, Role of Kynurenine Pathway in Oxidative Stress during Neurodegenerative Disorders - (Full text)
 * 2021, Tryptophan Metabolites, Cytokines, and Fatty Acid Binding Protein 2 in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome - (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)