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Record Information
Version5.0
StatusDetected and Quantified
Creation Date2005-11-16 15:48:42 UTC
Update Date2021-09-07 16:45:29 UTC
HMDB IDHMDB0001238
Secondary Accession Numbers
  • HMDB0061066
  • HMDB01238
  • HMDB61066
Metabolite Identification
Common NameN-Acetylserotonin
DescriptionN-Acetylserotonin (NAS), also known as normelatonin, is a naturally occurring chemical precursor and intermediate in the endogenous production of melatonin from serotonin. It also has biological activity in its own right, including acting as a melatonin receptor agonist, an agonist of the TrkB, and having antioxidant effects. N-Acetylserotonin is an intermediate in the metabolic pathway of melatonin and indoleamine in the pineal gland of mammalians. Serotonin-N-acetyltransferase (SNAT), which regulates the rate of melatonin biosynthesis in the pineal gland, catalyzes the acetylation of 5HT to N-acetylserotonin (NAS). A methyl group from S-adenosylmethionine is transferred to NAS by hydroxyindole-O-methyltransferase (HIOMT), and finally NAS is converted to 5-methoxy-N-acetyltryptamine, or melatonin. In most mammalian species the content of NAS (and melatonin) in the pineal gland shows clear circadian changes with the highest level occurring during the dark period. This elevation of the contents of NAS (and melatonin) in the dark period is due to the increase of SNAT activity and the elevation of SNAT gene expression. Experimental studies show that N-acetylserotonin possess free radical scavenging activity. Acute administration of irreversible and reversible selective MAO-A inhibitors and high doses (or chronic administration of low doses) of relatively selective MAO-B inhibitors (but not of highly selective MAO-B inhibitors) suppressed MAO-A activity and stimulated N-acetylation of pineal serotonin into N-acetylserotonin, the immediate precursor of melatonin. N-acetylserotonin increase after MAO-A inhibitors might mediate their antidepressive and antihypertensive effects. N-Acetylserotonin is the product of the O-demethylation of melatonin mediated by cytochrome P-450 isoforms: Cytochrome p450, subfamily IIc, polypeptide 19 (CYP2C19, a clinically important enzyme that metabolizes a wide variety of drugs), with a minor contribution from Cytochrome p450, subfamily I, polypeptide (2CYP1A2, involved in O-deethylation of phenacetin). (PMID 15616152 , 11103901 , 10721079 , 10591054 ). N-Acetylserotonin acts as a potent antioxidant, NAS effectiveness as an anti-oxidant has been found to be different depending on the experimental model used, it has been described as being between 5 and 20 times more effect than melatonin at protecting against oxidant damage. NAS has been shown to protect against lipid peroxidation in microsomes and mitochondria. NAS has also been reported to lower resting levels of ROS in peripheral blood lymphocytes and to exhibit anti-oxidant effects against t-butylated hydroperoxide- and diamide-induced ROS.
Structure
Data?1582752186
Synonyms
ValueSource
N-(2-(5-Hydroxy-1H-indol-3-yl)ethyl)acetamideChEBI
N-Acetyl-5-hydroxytryptamineChEBI
5-Hydroxy-N-acetyltryptamineHMDB
5-HydroxymelatoninHMDB
ASEHMDB
DesmethylmelatoninHMDB
O-DemethylmelatoninHMDB
N-AcetylhydroxytryptamineHMDB
Chemical FormulaC12H14N2O2
Average Molecular Weight218.2518
Monoisotopic Molecular Weight218.105527702
IUPAC NameN-[2-(5-hydroxy-1H-indol-3-yl)ethyl]acetamide
Traditional NameN-acetylserotonin
CAS Registry Number1210-83-9
SMILES
CC(=O)NCCC1=CNC2=C1C=C(O)C=C2
InChI Identifier
InChI=1S/C12H14N2O2/c1-8(15)13-5-4-9-7-14-12-3-2-10(16)6-11(9)12/h2-3,6-7,14,16H,4-5H2,1H3,(H,13,15)
InChI KeyMVAWJSIDNICKHF-UHFFFAOYSA-N
Chemical Taxonomy
Description Belongs to the class of organic compounds known as hydroxyindoles. These are organic compounds containing an indole moiety that carries a hydroxyl group.
KingdomOrganic compounds
Super ClassOrganoheterocyclic compounds
ClassIndoles and derivatives
Sub ClassHydroxyindoles
Direct ParentHydroxyindoles
Alternative Parents
Substituents
  • Hydroxyindole
  • 3-alkylindole
  • Indole
  • 1-hydroxy-2-unsubstituted benzenoid
  • Substituted pyrrole
  • Benzenoid
  • Pyrrole
  • Heteroaromatic compound
  • Carboximidic acid
  • Carboximidic acid derivative
  • Azacycle
  • Propargyl-type 1,3-dipolar organic compound
  • Organic 1,3-dipolar compound
  • Organic oxygen compound
  • Organooxygen compound
  • Organopnictogen compound
  • Hydrocarbon derivative
  • Organic nitrogen compound
  • Organonitrogen compound
  • Aromatic heteropolycyclic compound
Molecular FrameworkAromatic heteropolycyclic compounds
External Descriptors
Ontology
Physiological effect

Health effect:

Disposition

Route of exposure:

Source:

Biological location:

Process

Naturally occurring process:

Role

Industrial application:

Biological role:

Physical Properties
StateSolid
Experimental Properties
PropertyValueReference
Melting PointNot AvailableNot Available
Boiling PointNot AvailableNot Available
Water SolubilityNot AvailableNot Available
LogPNot AvailableNot Available
Predicted Properties
PropertyValueSource
Water Solubility0.57 g/LALOGPS
logP0.98ALOGPS
logP1ChemAxon
logS-2.6ALOGPS
pKa (Strongest Acidic)9.56ChemAxon
pKa (Strongest Basic)-1.6ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count2ChemAxon
Hydrogen Donor Count3ChemAxon
Polar Surface Area65.12 ŲChemAxon
Rotatable Bond Count3ChemAxon
Refractivity61.8 m³·mol⁻¹ChemAxon
Polarizability23.59 ųChemAxon
Number of Rings2ChemAxon
BioavailabilityYesChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleNoChemAxon
Spectra

GC-MS

Spectrum TypeDescriptionSplash KeyDeposition DateView
GC-MSGC-MS Spectrum - GC-EI-TOF (Pegasus III TOF-MS system, Leco; GC 6890, Agilent Technologies) (Non-derivatized)splash10-0f6x-0692000000-96e09fa6d98b96bcf1e42014-06-16View Spectrum
GC-MSGC-MS Spectrum - GC-EI-TOF (Pegasus III TOF-MS system, Leco; GC 6890, Agilent Technologies) (Non-derivatized)splash10-0fsm-0950000000-1bfd0dec31c3cbabefdd2014-06-16View Spectrum
GC-MSGC-MS Spectrum - GC-EI-TOF (Pegasus III TOF-MS system, Leco; GC 6890, Agilent Technologies) (Non-derivatized)splash10-0udl-0495000000-4408ea40213cdc89bf392014-06-16View Spectrum
GC-MSGC-MS Spectrum - GC-EI-TOF (Pegasus III TOF-MS system, Leco; GC 6890, Agilent Technologies) (Non-derivatized)splash10-0159-0690000000-15c09141663fccc3546f2014-06-16View Spectrum
GC-MSGC-MS Spectrum - GC-MS (3 TMS)splash10-0f6x-1592000000-742cca756ead515036262014-06-16View Spectrum
GC-MSGC-MS Spectrum - GC-MS (2 TMS)splash10-0f6x-2695000000-c377bb4d833e7c3880da2014-06-16View Spectrum
GC-MSGC-MS Spectrum - GC-MS (Non-derivatized)splash10-0f6x-1592000000-742cca756ead515036262017-09-12View Spectrum
GC-MSGC-MS Spectrum - GC-MS (Non-derivatized)splash10-0f6x-2695000000-c377bb4d833e7c3880da2017-09-12View Spectrum
GC-MSGC-MS Spectrum - GC-EI-TOF (Non-derivatized)splash10-0f6x-0692000000-60b556c70b30588d69f42017-09-12View Spectrum
GC-MSGC-MS Spectrum - GC-EI-TOF (Non-derivatized)splash10-0f6x-0595000000-687eb11cf30796ac93212017-09-12View Spectrum
GC-MSGC-MS Spectrum - GC-EI-TOF (Non-derivatized)splash10-0159-0590000000-3fa8283c51c6d0bcbb542017-09-12View Spectrum
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, Positivesplash10-0097-5910000000-ceaf51e6bbefe55372582017-08-28View Spectrum
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (1 TMS) - 70eV, Positivesplash10-00dl-9280000000-17099861a602d813f1952017-10-06View Spectrum
MSMass Spectrum (Electron Ionization)splash10-006x-9810000000-ab52a0c94944195a70ba2021-09-05View Spectrum

LC-MS/MS

Spectrum TypeDescriptionSplash KeyDeposition DateView
LC-MS/MSLC-MS/MS Spectrum - Quattro_QQQ 10V, Positive (Annotated)splash10-03di-0920000000-9c0d187c13aabfa510d92012-07-24View Spectrum
LC-MS/MSLC-MS/MS Spectrum - Quattro_QQQ 25V, Positive (Annotated)splash10-03di-0900000000-025ebd6d665bfe7141d32012-07-24View Spectrum
LC-MS/MSLC-MS/MS Spectrum - Quattro_QQQ 40V, Positive (Annotated)splash10-014i-1900000000-cdac2a24252af2ce8c652012-07-24View Spectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-qTof , Positivesplash10-03yi-2900000000-4fc1ad68abd1d25885272017-09-14View Spectrum
LC-MS/MSLC-MS/MS Spectrum - , negativesplash10-0aor-3890000000-f3ae8731ba8f76a62c232017-09-14View Spectrum
LC-MS/MSLC-MS/MS Spectrum - , positivesplash10-03yi-2900000000-4fc1ad68abd1d25885272017-09-14View Spectrum
LC-MS/MSLC-MS/MS Spectrum - , positivesplash10-03di-0900000000-73493993faa05c0e2d482017-09-14View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Positivesplash10-00or-0950000000-524beb3c0eb569b36af42017-07-25View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Positivesplash10-004i-0900000000-a01ac35d32e9651b0b182017-07-25View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Positivesplash10-01qd-1900000000-23a4306d4e9b966e41412017-07-25View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Negativesplash10-014i-1590000000-6be0bcac0c1150048e432017-07-26View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Negativesplash10-00os-3920000000-16b240b30f4e9fb80a102017-07-26View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Negativesplash10-052f-9300000000-60ab04a4c74a12a09ddd2017-07-26View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Negativesplash10-014j-4790000000-dac3da3126026a5a6d0d2021-09-08View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Negativesplash10-001i-2910000000-d71ef8cf4f2fff8c4a932021-09-08View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Negativesplash10-000x-9600000000-4585286d1ca68491fd572021-09-08View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Positivesplash10-02t9-0980000000-47768c7e3ebb75268cd42021-09-08View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Positivesplash10-03di-0900000000-46832f14387d1f4670292021-09-08View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Positivesplash10-000x-1900000000-1a76773bb3073cd055f62021-09-08View Spectrum

NMR

Spectrum TypeDescriptionDeposition DateView
1D NMR1H NMR Spectrum (1D, 500 MHz, CDCl3, experimental)2012-12-04View Spectrum
2D NMR[1H, 13C] NMR Spectrum (2D, 600 MHz, CD3OD, predicted)2012-12-05View Spectrum
Biological Properties
Cellular Locations
  • Cytoplasm
  • Membrane
Biospecimen Locations
  • Blood
  • Feces
  • Urine
Tissue Locations
  • Kidney
  • Liver
Pathways
Normal Concentrations
BiospecimenStatusValueAgeSexConditionReferenceDetails
BloodDetected and Quantified0.0054 uMAdult (>18 years old)Both
Normal
details
BloodDetected but not QuantifiedNot QuantifiedAdult (>18 years old)BothNormal details
BloodExpected but not QuantifiedNot QuantifiedNot AvailableNot AvailableNormal
      Not Available
details
FecesDetected but not QuantifiedNot QuantifiedAdult (>18 years old)Both
Normal
details
UrineDetected but not QuantifiedNot QuantifiedAdult (>18 years old)BothNormal details
UrineExpected but not QuantifiedNot QuantifiedNot AvailableNot AvailableNormal
      Not Available
details
Abnormal Concentrations
BiospecimenStatusValueAgeSexConditionReferenceDetails
BloodDetected and Quantified0.011 uMAdult (>18 years old)Both
Schizophrenia
details
Associated Disorders and Diseases
Disease References
Schizophrenia
  1. Yao JK, Dougherty GG Jr, Reddy RD, Keshavan MS, Montrose DM, Matson WR, Rozen S, Krishnan RR, McEvoy J, Kaddurah-Daouk R: Altered interactions of tryptophan metabolites in first-episode neuroleptic-naive patients with schizophrenia. Mol Psychiatry. 2010 Sep;15(9):938-53. doi: 10.1038/mp.2009.33. Epub 2009 Apr 28. [PubMed:19401681 ]
Associated OMIM IDs
DrugBank IDDB04275
Phenol Explorer Compound IDNot Available
FooDB IDFDB022505
KNApSAcK IDNot Available
Chemspider ID879
KEGG Compound IDC00978
BioCyc IDN-ACETYL-SEROTONIN
BiGG ID36527
Wikipedia LinkN-acetyl-serotonin
METLIN ID366
PubChem Compound903
PDB IDNot Available
ChEBI ID17697
Food Biomarker OntologyNot Available
VMH IDNot Available
MarkerDB IDNot Available
References
Synthesis ReferenceBalemans M G; Mans D; Smith I; Van Benthem J The influence of GABA on the synthesis of N-acetylserotonin, melatonin, O-acetyl-5-hydroxytryptophol and O-acetyl-5-methoxytryptophol in the pineal gland of the male Wistar rat. Reproduction, nutrition, development (1983), 23(1), 151-60.
Material Safety Data Sheet (MSDS)Download (PDF)
General References
  1. Ma X, Idle JR, Krausz KW, Gonzalez FJ: Metabolism of melatonin by human cytochromes p450. Drug Metab Dispos. 2005 Apr;33(4):489-94. Epub 2004 Dec 22. [PubMed:15616152 ]
  2. Harumi T, Matsushima S: Separation and assay methods for melatonin and its precursors. J Chromatogr B Biomed Sci Appl. 2000 Sep 29;747(1-2):95-110. [PubMed:11103901 ]
  3. Reiter RJ, Tan DX, Cabrera J, D'Arpa D: Melatonin and tryptophan derivatives as free radical scavengers and antioxidants. Adv Exp Med Biol. 1999;467:379-87. [PubMed:10721079 ]
  4. Oxenkrug GF: Antidepressive and antihypertensive effects of MAO-A inhibition: role of N-acetylserotonin. A review. Neurobiology (Bp). 1999;7(2):213-24. [PubMed:10591054 ]
  5. Brunk E, Sahoo S, Zielinski DC, Altunkaya A, Drager A, Mih N, Gatto F, Nilsson A, Preciat Gonzalez GA, Aurich MK, Prlic A, Sastry A, Danielsdottir AD, Heinken A, Noronha A, Rose PW, Burley SK, Fleming RMT, Nielsen J, Thiele I, Palsson BO: Recon3D enables a three-dimensional view of gene variation in human metabolism. Nat Biotechnol. 2018 Mar;36(3):272-281. doi: 10.1038/nbt.4072. Epub 2018 Feb 19. [PubMed:29457794 ]

Enzymes

General function:
Involved in N-acetyltransferase activity
Specific function:
Controls the night/day rhythm of melatonin production in the pineal gland. Catalyzes the N-acetylation of serotonin into N-acetylserotonin, the penultimate step in the synthesis of melatonin.
Gene Name:
AANAT
Uniprot ID:
Q16613
Molecular weight:
23343.8
Reactions
Acetyl-CoA + Serotonin → Coenzyme A + N-Acetylserotonindetails
General function:
Involved in O-methyltransferase activity
Specific function:
Isoform 1 catalyzes the transfer of a methyl group onto N-acetylserotonin, producing melatonin (N-acetyl-5-methoxytryptamine). Isoform 2 and isoform 3 lack enzyme activity.
Gene Name:
ASMT
Uniprot ID:
P46597
Molecular weight:
41660.34
Reactions
S-Adenosylmethionine + N-Acetylserotonin → S-Adenosylhomocysteine + Melatonindetails