title: Tryptophan-kynurenine pathway is dysregulated in inflammation, and immune activation.
abstract: The kynurenine (Kyn) pathway is the major route for tryptophan (Trp) metabolism, and it contributes to several fundamental biological processes. Trp is constitutively oxidized by tryptophan 2, 3-dioxygenase in liver cells. In other cell types, it is catalyzed by an alternative inducible indoleamine-pyrrole 2, 3-dioxygenase (IDO) under certain pathophysiological conditions, which consequently increases the formation of Kyn metabolites. IDO is up-regulated in response to inflammatory conditions as a novel marker of immune activation in early atherosclerosis. Besides, IDO and the IDO-related pathway are important mediators of the immunoinflammatory responses in advanced atherosclerosis. In particular, Kyn, 3-hydroxykynurenine, and quinolinic acid are positively associated with inflammation, oxidative stress (SOX), endothelial dysfunction, and carotid artery intima-media thickness values in end-stage renal disease patients. Moreover, IDO is a potential novel contributor to vessel relaxation and metabolism in systemic infections, which is also activated in acute severe heart attacks. The Kyn pathway plays a key role in the increased prevalence of cardiovascular disease by regulating inflammation, SOX, and immune activation.
authors.forename: Qiongxin
authors.initials: Q
authors.lastname: Wang
authors.forename: Danxia
authors.initials: D
authors.lastname: Liu
authors.forename: Ping
authors.initials: P
authors.lastname: Song
authors.affiliation: Division of Molecular Medicine, Department of Medicine, and Department of Biochemistry and Molecular Biology, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104, USA, ming-hui-zou@ouhsc.edu.
authors.forename: Ming-Hui
authors.initials: MH
authors.lastname: Zou
mesh_terms: D000328:Adult; D000368:Aged; D000818:Animals; D002318:Cardiovascular Diseases / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D005260:Female; D006801:Humans; D007154:Immune System Diseases / Q000378:metabolism* / Q000473:pathology; D007249:Inflammation / Q000378:metabolism*; D007674:Kidney Diseases / Q000378:metabolism* / Q000473:pathology; D007737:Kynurenine / Q000378:metabolism*; D008297:Male; D008322:Mammals; D053858:Metabolic Networks and Pathways; D008875:Middle Aged; D018384:Oxidative Stress; D011817:Rabbits; D051381:Rats; D014364:Tryptophan / Q000378:metabolism*; D055815:Young Adult
chemical_list: D007737:Kynurenine; D014364:Tryptophan