Melatonin and 5-methoxytryptamine in non-metazoans

Hardeland, Rüdiger

doi:10.1051/rnd:19990311

Cited by 91 publications

(97 citation statements)

References 14 publications

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“…In general, melatonin deacetylating enzymes can be classified as aryl acylamidases (AAAs). Although the conversion of melatonin to 5-MT by these enzymes seems to be important in organisms different from animals, such as dinoflagellates [37,45] and yeast [129], the quantitative significance of this pathway has only become apparent in the retinas of some amphibians, reptiles and fish [19,32,34]. In other retinas in which AA-NAT is strongly expressed, but only small amounts of melatonin are detected, melatonin deacetylation may be considered, too, as long as the low melatonin levels are not attributable to poor Omethylation.…”

Section: Melatonin Deacetylationmentioning

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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Section: Melatonin Deacetylationmentioning

confidence: 99%

Melatonin Metabolism in the Central Nervous System

Hardeland¹

2010

114

110

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“…In addition to its presence in vertebrates, melatonin is also found in bacteria, unicellular organisms, fungi and plants (Manchester et al, 1995;Poeggeler et al, 1991;Hardeland, 1999;Reiter et al, 2001). It seems that melatonin may have evolved in all evolutionary life forms from simplest bacteria to humans.…”

Section: Introductionmentioning

confidence: 99%

Melatonin in Chinese medicinal herbs

et al. 2003

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“…Similarity is limited primarily to the catalytic core of vertebrate AANAT and is highest within motifs A/B, which characterize the GNAT superfamily (1,4). The presence of AANAT in S. cerevisiae is of special interest because, if it had arylalkylamine N-acetyltransferase activity, it could participate in the formation of melatonin (5,6); it could also have a broader function in detoxification of arylalkylamines.…”

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confidence: 99%

Characterization of the Saccharomyces cerevisiae Homolog of the Melatonin Rhythm Enzyme Arylalkylamine N-Acetyltransferase (EC 2.3.1.87)

Ganguly

Mummaneni

Steinbach

et al. 2001

Journal of Biological Chemistry

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Arylalkylamine N-acetyltransferase (AANAT, serotonin N-acetyltransferase, EC 2.3.1.87) plays a unique transduction role in vertebrate physiology by converting information about day and night into a hormonal signal: melatonin. Only vertebrate members of the AANAT family have been functionally characterized. Here a putative AANAT from Saccharomyces cerevisiae (scAANAT) was studied to determine whether it possessed the catalytic activity of the vertebrate enzyme. scAANAT is 47% similar to ovine AANAT, but lacks the regulatory N-and C-terminal flanking regions conserved in all vertebrate AANATs. It was found to have enzyme activity generally typical for AANAT family members, although the substrate preference pattern was somewhat broader, the specific activity was lower, and the pH optimum was higher. Deletion of scAANAT reduced arylalkylamine acetylation by S. cerevisiae extracts, indicating that scAANAT contributes significantly to this process. The scAANAT sequence conformed to the three-dimensional structure of ovine AANAT catalytic core; however, an important structural element (loop 1) was found to be shorter and to lack a proline involved in substrate binding. These differences could explain the lower specific activity of scAANAT, because of the importance of loop 1 in catalysis. Data base analysis revealed the presence of putative AANATs in other fungi but not in the nearly complete genomes of Drosophila melanogaster or Caenorhabditis elegans. These studies indicate that the catalytic and kinetic characteristics of fungal and vertebrate enzymes can be considered to be generally similar, although some differences exist that appear to be linked to changes in one structural element. Perhaps the most striking difference is that fungal AANATs lack the regulatory domains of the vertebrate enzyme, which appear to be essential for the regulatory role the enzyme plays in photochemical transduction.The arylalkylamine N-acetyltransferase (serotonin N-acetyltransferase, AANAT, 1 EC 2.3.1.87) family is part of the motif A/B or GNAT acetyltransferase superfamily, which includes over 250 members (1-3). This superfamily is represented in all phyla, and each family selectively acetylates a substrate group; substrates range in size from proteins to aminoglycosides, diamines, and small amines. The AANAT family exhibits selectivity for arylalkylamines, including serotonin, tryptamine, and phenylethylamine (1). Functional members of the AANAT family have only been identified in vertebrates. Vertebrate AANAT is closely associated with photochemical transduction, specifically melatonin synthesis (serotonin 3 Nacetylserotonin 3 melatonin). It is expressed at significant levels in the two tissues in which melatonin is synthesized, the pineal gland (the source of circulating melatonin) and the retina (where melatonin acts locally). In both tissues, the activity of the enzyme is under complex regulation; changes in AANAT activity control the precise day/night rhythm in melatonin production (reviewed in Ref. 2). Accordingly, vertebrate ...

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Melatonin and 5-methoxytryptamine in non-metazoans

Abstract: -Melatonin seems to be an almost ubiquitous substance, which has been detected not only in metazoans, but also in all major non-metazoan taxa investigated, including bacteria

Cited by 91 publications

References 14 publications

Melatonin Metabolism in the Central Nervous System

Melatonin Metabolism in the Central Nervous System

Melatonin in Chinese medicinal herbs

Characterization of the Saccharomyces cerevisiae Homolog of the Melatonin Rhythm Enzyme Arylalkylamine N-Acetyltransferase (EC 2.3.1.87)

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