Novel pathway for N1‐acetyl‐5‐methoxykynuramine: UVB‐induced liberation of carbon monoxide from precursor N 1‐acetyl‐N 2‐formyl‐5‐methoxykynuramine

Seever, Katinka; Hardeland, Rüdiger

doi:10.1111/j.1600-079x.2007.00550.x

Cited by 17 publications

(16 citation statements)

References 36 publications

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“…In the kynuric pathway, melatonin can be converted either enzymatically or non-enzymatically to N1-acetyl-N2-formyl-5-methoxykynuramine (AFMK), in a process that encompasses generation of 3-hydroxymelatonin, 2-hydroxymelatonin, melatonin 2-indolinone, 3-hydroxymelatonin, 2-indolinone, and melatonin dioxetane as intermediate products (Hardeland et al, 2009, Hirata et al, 1974, Reiter et al, 2007). AFMK synthesis involves enzymes or pseudoenzymes such as cytochrome c, horseradish peroxidase, indoleamine dioxygenase, myeloperoxidase, oxoferryl hemoglobin or hemin as well as non-enzymatic pathway that may be activated in the presence of reactive oxygen species (ROS) or UVB (Fischer et al, 2006a, Hardeland et al, 2009, Kanda and Watanabe, 2007, Seever and Hardeland, 2008, Semak et al, 2008, Semak et al, 2005). In addition, catalase, arylamine formamidase, hemoperoxidase and ROS can stimulate the conversion of AFMK to AMK (Hardeland et al, 2009, Kanda and Watanabe, 2007, Reiter et al, 2007).…”

Section: Melatoninergic System In the Skinmentioning

confidence: 99%

Introduction

Słomiński

Żmijewski

Skobowiat

et al. 2012

Advances in Anatomy, Embryology and Cell Biology

427

136

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Section: Melatoninergic System In the Skinmentioning

confidence: 99%

Introduction

Słomiński

Żmijewski

Skobowiat

et al. 2012

Advances in Anatomy, Embryology and Cell Biology

427

136

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“…Recently, another photochemical mechanism by UV light (Fig. 2) has been described [122]. AMK formation may not be an exclusive route of AFMK metabolism, since free-radical reactions also led to a couple of C2-substituted 3-indolinones (Fig.…”

mentioning

confidence: 99%

Melatonin, hormone of darkness and more – occurrence, control mechanisms, actions and bioactive metabolites

Hardeland

2008

Cell. Mol. Life Sci.

222

202

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In its role as a pineal hormone, melatonin is a pleiotropic, nocturnally peaking and systemically acting chronobiotic. These effects are largely explained by actions via G protein-coupled membrane receptors found in the suprachiasmatic nucleus, but also in numerous other sites. Nuclear (ROR/RZR), cytoplasmic (quinone reductase-2, calmodulin, calreticulin) and mitochondrial binding sites and radical-scavenging properties contribute to the actions of melatonin. Regulation of pineal melatonin biosynthesis is largely explained by control mechanisms acting on arylalkylamine N-acetyltransferase, at the levels of gene expression and/or enzyme stability influenced by phosphorylation and interaction with 14-3-3 proteins. Melatonin is not only a hormone but is also synthesized in numerous extrapineal sites, in which it sometimes attains much higher quantities than in the pineal and the circulation. It is also present in many taxonomically distant groups of organisms, including bacteria, fungi, and plants. Moreover, melatonin is a source of bioactive metabolites, such as 5-methoxytryptamine, N(1)-acetyl-N(2)-formyl-5-methoxykynuramine and N(1)-acetyl-5-methoxykynuramine.

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“…One of them, a photochemical reaction [120], should be irrelevant to the brain, but may occur in the eye. Another, long-known reaction is catalyzed by arylamine formamidases, a group of enzymes, some of which have a relatively low substrate specificity [49,50,62].…”

Section: The Kynuramine Pathwaymentioning

confidence: 99%

Melatonin Metabolism in the Central Nervous System

Hardeland¹

2010

114

110

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Abstract:The metabolism of melatonin in the central nervous system is of interest for several reasons. Melatonin enters the brain either via the pineal recess or by uptake from the blood. It has been assumed to be also formed in some brain areas. Neuroprotection by melatonin has been demonstrated in numerous model systems, and various attempts have been undertaken to counteract neurodegeneration by melatonin treatment. Several concurrent pathways lead to different products. Cytochrome P 450 subforms have been demonstrated in the brain. They either demethylate melatonin to Nacetylserotonin, or produce 6-hydroxymelatonin, which is mostly sulfated already in the CNS. Melatonin is deacetylated, at least in pineal gland and retina, to 5-methoxytryptamine. N 1 -acetyl-N 2 -formyl-5-methoxykynuramine is formed by pyrrole-ring cleavage, by myeloperoxidase, indoleamine 2,3-dioxygenase and various non-enzymatic oxidants. Its product, N 1 -acetyl-5-methoxykynuramine, is of interest as a scavenger of reactive oxygen and nitrogen species, mitochondrial modulator, downregulator of cyclooxygenase-2, inhibitor of cyclooxygenase, neuronal and inducible NO synthases. Contrary to other nitrosated aromates, the nitrosated kynuramine metabolite, 3-acetamidomethyl-6-methoxycinnolinone, does not re-donate NO. Various other products are formed from melatonin and its metabolites by interaction with reactive oxygen and nitrogen species. The relative contribution of the various pathways to melatonin catabolism seems to be influenced by microglia activation, oxidative stress and brain levels of melatonin, which may be strongly changed in experiments on neuroprotection. Many of the melatonin metabolites, which may appear in elevated concentrations after melatonin administration, possess biological or pharmacological properties, including N-acetylserotonin, 5-methoxytryptamine and some of its derivatives, and especially the 5-methoxylated kynuramines.

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Novel pathway for N¹‐acetyl‐5‐methoxykynuramine: UVB‐induced liberation of carbon monoxide from precursor N¹‐acetyl‐N²‐formyl‐5‐methoxykynuramine

Cited by 17 publications

References 36 publications

Introduction

Introduction

Melatonin, hormone of darkness and more – occurrence, control mechanisms, actions and bioactive metabolites

Melatonin Metabolism in the Central Nervous System

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