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Melatonin: A “Guardian” of the Genome and Cellular Integrity for Prevention of Photocarcinogenesis
Published in Andreia Ascenso, Sandra Simões, Helena Ribeiro, Carrier-Mediated Dermal Delivery, 2017
Patricia Manteigas, Andreia Ascenso
The kynuric pathway metabolizes the melatonin through two forms: enzymatic and non-enzymatic, the last one being involved in the action of free radicals or ultraviolet B (UVB) radiation. Moreover, non-enzymatic reactions with free radicals, in particular the superoxide anion and the hydroxyl radicals, represent a significant aspect of melatonin’s biological role, which will be explained in detail in the chapter—melatonin as a “guardian” for prevention of photocarcinogenesis [47]. In enzymatic reactions, melatonin is metabolized by indoleamine 2,3 dioxygenase to produce W-acetyl-W-formyl-5-methox- ykynuramine (AFMK). AFMK is further metabolized by arylamine formamidase to N-acetyl-5-methoxykynuramine (AMK). Posteriorly, AMK can produce two different metabolites: AAMC or MQA by reacting with either NO+, NO, or HNO or with carbamoyl phosphate, H2O2 and Cu2+, respectively [2,6,31].
Tryptophan 2,3-dioxygenase, a novel therapeutic target for Parkinson’s disease
Published in Expert Opinion on Therapeutic Targets, 2021
Fanni Annamária Boros, László Vécsei
The first step of the KP is the conversion of Trp into N-formyl-L-kynurenine in a reaction catalyzed by indoleamine 2,3-dioxygenase 1 and 2 (IDO1 and IDO2) and tryptophan 2,3-dioxygenase (TDO) enzymes. N-formyl-L-kynurenine is then metabolized into L-kynurenine (KYN) by formamidase. KYN is situated at an important branch point of the KP, since it can be converted into i) kynurenic acid (KYNA) by kynurenine aminotransferases (KATs), ii) anthranilic acid (AA) by kynureninase (KYNU), and iii) 3-hydroxykynurenine (3-HK) via a reaction catalyzed by kynurenine 3-monooxygenase (KMO). 3HK can further be metabolized into xanthurenic acid (XA) by KATs or can form 3-hydroxyanthranilate (3-HAA), which is further converted into 2-amino-3-carboxymuconate semialdehyde (ACMS) in a reaction catalyzed by 3-hydroxyanthranilate 3,4-dioxygenase. ACMS can be further processed by aminocarboxymuconate-semialdehyde decarboxylase (ACMSD) for the synthesis of 2-aminomuconate semialdehyde, which is then further metabolized into picolinic acid (PIC). ACMS can also undergo non-enzymatic cyclization and form quinolinic acid (QUIN), which is then ultimately metabolized into nicotinamide adenine dinucleotide (NAD+), a crucial molecule for cellular energy production and metabolism.
Gut dysbiosis induced by cardiac pressure overload enhances adverse cardiac remodeling in a T cell-dependent manner
Published in Gut Microbes, 2020
Francisco J Carrillo-Salinas, Marina Anastasiou, Njabulo Ngwenyama, Kuljeet Kaur, Albert Tai, Sasha A. Smolgovsky, David Jetton, Mark Aronovitz, Pilar Alcaide
The gut is one of the main reservoirs of T cells in the body, which are in close contact with gut bacteria to maintain homeostatic control of local and systemic immunity. This is often mediated by metabolites processed by the gut microbiota.8–10 These metabolites include short-chain fatty acids (SCFAs) and tryptophan derivatives, which are further metabolized by the mammalian enzymes indoleamine 2, 3-dioxygenase (IDO1), and kynurenine formamidase (AFMID), and activate the SCFA receptors and aryl hydrocarbon receptor (AhR), respectively, in host cells, and modulate homeostatic immune responses. Disruption of this process can lead to over-activation of T cells in the gut lamina propria and influence immune responses in distant sites during chronic inflammatory responses.11
Indoleamine 2,3-dioxygenase as a novel therapeutic target for Huntington’s disease
Published in Expert Opinion on Therapeutic Targets, 2019
Fanni A. Boros, Péter Klivényi, József Toldi, László Vécsei
The product of the first enzymatic conversion of the KP, N-formyl-L-kynurenine is converted by formamidase into L-kynurenine (L-KYN). L-KYN represents an important branch point of the pathway as it can be metabolized alternatively into kynurenic acid (KYNA), or anthranilic acid (AA), or 3-hydroxykynurenine (3-HK). KYNA is synthesized from L-KYN by kynurenine aminotransferases (KATs). There are four subtypes of KATs (KATI-IV) [40] that can catalyze the conversion. The principal enzyme from these in the human CNS is KATII [40,41]. Besides KATs, L-KYN can also be metabolized by the kynureninase enzyme (KYNU) and kynurenine 3-monooxygenase (KMO) forming AA or 3-HK, respectively. 3-HK can be metabolized into xanthurenic acid (XA) by KATs, and both AA and 3-HK can be converted into 3-hydroxyanthranilic acid (3-HAA), a metabolite which is a free radical generator (like other compounds of the pathway, see below) [20]. 3-HAA transforms into the unstable 2-amino-3-carboxymuconate-semialdehyde (ACMS) by 3–hydroxyanthranilate oxidase (3-HAO). ACMS can give rise to either picolinic acid (PIC) by conversion via aminocarboxymuconate-semialdehyde decarboxylase (ACMSD) or to QUIN, a NAD+ and NADP+ precursor metabolite, via a non-enzymatic conversion.