title: Heme-dependent dioxygenases in tryptophan oxidation.
abstract: L-Tryptophan is an essential amino acid for mammals. It is utilized not only for protein synthesis but also for the biosynthesis of serotonin and melatonin by the serotonin pathway as well as nicotinamide adenine dinucleotide by the kynurenine pathway. Although the kynurenine pathway is responsible for the catabolism of over 90% of l-tryptophan in the mammalian intracellular and extracellular pools, the scientific field was dominated in the last century by studies of the serotonin pathway, due to the physiological significance of the latter's catabolic intermediates and products. However, in the past decade, the focus gradually reversed as the link between the kynurenine pathway and various neurodegenerative disorders and immune diseases is increasingly highlighted. Notably, the first step of this pathway, which is catalyzed by heme-dependent dioxygenases, has been proven to be a potential target for immune regulation and cancer treatment. A thorough understanding of the intriguing chemistry of the heme-dependent dioxygenases may yield insight for the drug discovery of these prevalent illnesses. In this review, we survey enzymatic and mechanistic studies, initially started by Kotake and Masayama over 70 years ago, at the molecular level on the heme-dependent tryptophan dioxygenation reactions.
authors.affiliation: Department of Chemistry, Georgia State University, 50 Decatur Street SE, Atlanta, GA 30303, United States.
authors.forename: Jiafeng
authors.initials: J
authors.lastname: Geng
authors.affiliation: Department of Chemistry, Georgia State University, 50 Decatur Street SE, Atlanta, GA 30303, United States. Electronic address: Feradical@gsu.edu.
authors.forename: Aimin
authors.initials: A
authors.lastname: Liu
mesh_terms: D000818:Animals; D006418:Heme / Q000737:chemistry / Q000378:metabolism*; D006801:Humans; D006861:Hydrogen Peroxide / Q000737:chemistry / Q000378:metabolism; D008958:Models, Molecular; D010100:Oxygen / Q000737:chemistry / Q000378:metabolism; D014364:Tryptophan / Q000737:chemistry / Q000378:metabolism*; D014366:Tryptophan Oxygenase / Q000737:chemistry / Q000378:metabolism*
chemical_list: D006418:Heme; D014364:Tryptophan; D006861:Hydrogen Peroxide; D014366:Tryptophan Oxygenase; D010100:Oxygen
keywords: Free radical; High-valence iron; Metalloprotein; Oxygen activation; Peroxide reaction; Reactive oxygen species