An Emerging Cross-Species Marker for Organismal Health: Tryptophan-Kynurenine Pathway

International Journal of Molecular Sciences

Gregg T. Tomy¹  Jade V. Wish¹  Laiba Jamshed²  Amrita Debnath²  Shanza Jamshed²  Alison C. Holloway²  Philippe J. Thomas³  Jason C. Raine⁴ 

[1] Department of Chemistry, Centre for Oil and Gas Research and Development (COGRAD), University of Manitoba, 586 Parker Building, 144 Dysart Rd., Winnipeg, MB R3T 2N2, Canada;Department of Obstetrics and Gynecology, McMaster University, Hamilton, ON L8S 4K1, Canada;Environment and Climate Change Canada, National Wildlife Research Centre, Ottawa, ON K1A 0H3, Canada;Quesnel River Research Centre, University of Northern British Columbia, Prince George, BC V2N 4Z9, Canada;

关键词: tryptophan;    kynurenine;    metabolites;    glucocorticoids;    stress;    inflammation;   

DOI  :  10.3390/ijms23116300

来源: DOAJ

【 摘 要 】

Tryptophan (TRP) is an essential dietary amino acid that, unless otherwise committed to protein synthesis, undergoes metabolism via the Tryptophan-Kynurenine (TRP-KYN) pathway in vertebrate organisms. TRP and its metabolites have key roles in diverse physiological processes including cell growth and maintenance, immunity, disease states and the coordination of adaptive responses to environmental and dietary cues. Changes in TRP metabolism can alter the availability of TRP for protein and serotonin biosynthesis as well as alter levels of the immune-active KYN pathway metabolites. There is now considerable evidence which has shown that the TRP-KYN pathway can be influenced by various stressors including glucocorticoids (marker of chronic stress), infection, inflammation and oxidative stress, and environmental toxicants. While there is little known regarding the role of TRP metabolism following exposure to environmental contaminants, there is evidence of linkages between chemically induced metabolic perturbations and altered TRP enzymes and KYN metabolites. Moreover, the TRP-KYN pathway is conserved across vertebrate species and can be influenced by exposure to xenobiotics, therefore, understanding how this pathway is regulated may have broader implications for environmental and wildlife toxicology. The goal of this narrative review is to (1) identify key pathways affecting Trp-Kyn metabolism in vertebrates and (2) highlight consequences of altered tryptophan metabolism in mammals, birds, amphibians, and fish. We discuss current literature available across species, highlight gaps in the current state of knowledge, and further postulate that the kynurenine to tryptophan ratio can be used as a novel biomarker for assessing organismal and, more broadly, ecosystem health.

【 授权许可】

Unknown