[67] Arylalkylamine N-acetyltransferase from mammalian pineal gland

Namboodiri, M. A. A.; Dubbels, R.; Klein, David C.

doi:10.1016/s0076-6879(87)42069-7

Cited by 51 publications

(28 citation statements)

References 13 publications

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“…AANAT activity was measured radiochemically as described previously (1,9). Unless otherwise indicated, each assay contained tryptamine HCl (10 mM) and [ 3 H]AcCoA (0.5 mM; 4 Ci/mol; PerkinElmer Life Sciences).…”

Section: Assay Of Aanat Activitymentioning

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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Section: Assay Of Aanat Activitymentioning

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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“…In addition, kinetic analyses have revealed that the apparent Michaelis constants (K m ) for the substrates of rat ovary NAT and HIOMT were similar to those of the pineal gland (Sugden (Axelrod, 1974;Namboodiri et al, 1987;Sugden et al, 1987). and Klein, 1983;Namboodiri et al, 1987;Bernard et al, 1995;Itoh et al, 1997a), suggesting that rat ovary NAT and HIOMT function physiologically as melatonin-synthesizing enzymes.…”

Section: Introductionmentioning

confidence: 98%

“…Melatonin (N-acetyl-5-methoxytryptamine) is an indoleamine originally identified in the pineal gland, where it is synthesized enzymatically from serotonin (5-hydroxytryptamine) by the sequential action of arylalkylamine N-acetyltransferase (EC 2.3.1.87; NAT) and hydroxyindole-O-methyltransferase (EC 2.1.1.4; HIOMT) ( Figure 1; Axelrod, 1974;Namboodiri et al, 1987;Sugden et al, 1987). The synthesis and secretion of melatonin fluctuate in a circadian rhythm that is entrained to a 24 h light/dark cycle (Axelrod, 1974;Tamarkin et al, 1985;Bals-Pratsch et al, 1997;Brzezinski, 1997).…”

Section: Introductionmentioning

confidence: 99%

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Melatonin, its precursors, and synthesizing enzyme activities in the human ovary

Itoh

Ishizuka²,

Kuribayashi³

et al. 1999

Molecular Human Reproduction

159

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The presence of melatonin (N-acetyl-5-methoxytryptamine) and its precursors, serotonin (5-hydroxytryptamine) and N-acetylserotonin, was demonstrated in extracts of human ovary using reverse-phase highperformance liquid chromatography coupled with fluorometric detection. In addition, activities of two melatonin-synthesizing enzymes, arylalkylamine N-acetyltransferase (NAT) and hydroxyindole-O-methyltransferase (HIOMT), were found in human ovary homogenates. The apparent Michaelis constants for the substrates of NAT and HIOMT in the human ovary were similar to those reported for the pineal glands of humans and other mammals. These findings strongly suggest that the human ovary, like the pineal gland, may synthesize melatonin from serotonin by the sequential action of NAT and HIOMT.

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“…This process is accompanied by an increased activity of the rate-limiting enzyme in melatonin synthesis, arylalkylamine NAT that acetylates serotonin to NAS (1-3). These processes are stimulated by the rise in the intracellular concentrations of cAMP (1)(2)(3). It is of interest that in skin culture the highest production of [ -4)).…”

mentioning

confidence: 99%

Metabolism of Serotonin to N-Acetylserotonin, Melatonin, and 5-Methoxytryptamine in Hamster Skin Culture

Słomiński

Baker

Rosano

et al. 1996

Journal of Biological Chemistry

128

114

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Biotransformation of [3 H]serotonin by cultured hamster skin to 3 H-metabolites corresponding to N-acetylserotonin (NAS), melatonin, and 5-methoxytryptamine (5-MT) was demonstrated. This process was time-dependent, with the highest production of radioactive NAS and melatonin metabolites after 3 and 5 h of incubation followed by a decrease in the rate of metabolite release into the media. Conversely, the formation of radioactive metabolite corresponding to 5-MT increased gradually during skin culture, reaching the highest level after 24 h of incubation. The production of 3 H-metabolites, corresponding to NAS, melatonin, and 5-MT, was stimulated by forskolin with a maximum effect of forskolin at 10 M concentration. The gas chromatographic/mass spectroscopy analysis of the fraction eluting at the retention time of NAS standard material showed that it contained NAS, further confirming production and release of NAS into the media by hamster skin. Therefore, we conclude that mammalian skin can acetylate serotonin to NAS and postulate that the NAS is further metabolized by the skin to form melatonin which is subsequently transformed to 5-MT.Melatonin serves as the main signal molecule which links the photoperiod to metabolic, endocrine, and immunological changes and which is mainly synthesized in the pineal gland, retina, brain, and Harderian gland (1). Depending of the site of production and target organ it can act as a hormone, neurotransmitter, cytokine, and biological modifier (2).Melatonin is a product of a two-step conversion of serotonin, which involves the acetylation of serotonin (3) and subsequent methylation by hydroxyindole-O-methyltransferase (4). The majority of melatonin released into the bloodstream is metabolized in the liver and kidneys (5, 6), mainly by 6-hydroxylation and conjugation to glucuronate or sulfate (5, 6), and to a minor degree by deacetylation to 5-methoxytryptamine (5-MT), 1 which is further deaminated (5-7). In contrast, melatonin bioconversion at the organ site of synthesis appears to be different from the metabolism of circulating melatonin (8 -10). For example, in the retina melatonin is first deacetylated to 5-MT, which can then be deaminated, producing 5-methoxyindoleacetic acid and 5-methoxytryptophol (8, 9). Melatonin deacetylation to 5-MT was also detected in retinal pigment epithelium and non-mammalian skin that are target sites for melatonin bioregulation (8 -10). Extracranial sites of both synthesis and metabolism of melatonin have also been demonstrated in the peripheral blood mononuclear leukocytes (11), and according to some authors in the gastrointestinal tract (12).Melatonin production has not previously been demonstrated in skin, which is the largest body organ that can react to external and internal stimuli via the skin immune system (13), the pigmentary system (14), and the skin endocrine system (15, 16). In lower verterbrates skin is a recognized target for melatonin action, e.g. melatonin has lightening activity on the skin (17). In mammals, it has been reported th...

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[67] Arylalkylamine N-acetyltransferase from mammalian pineal gland

Cited by 51 publications

References 13 publications

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

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

Melatonin, its precursors, and synthesizing enzyme activities in the human ovary

Metabolism of Serotonin to N-Acetylserotonin, Melatonin, and 5-Methoxytryptamine in Hamster Skin Culture

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