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Record Information
Version3.6
Creation Date2005-11-16 15:48:42 UTC
Update Date2013-02-09 00:10:27 UTC
HMDB IDHMDB01389
Secondary Accession NumbersNone
Metabolite Identification
Common NameMelatonin
DescriptionMelatonin is a biogenic amine that is found in animals, plants and microbes. Aaron B.Lerner of Yale University is credited for naming the hormone and for defining its chemical structure in 1958. In mammals, melatonin is produced by the pineal gland. The pineal gland is small endocrine gland, about the size of a rice grain and shaped like a pine cone (hence the name), that is located in the center of the brain (rostro-dorsal to the superior colliculus) but outside the blood-brain barrier. The secretion of melatonin increases in darkness and decreases during exposure to light, thereby regulating the circadian rhythms of several biological functions, including the sleep-wake cycle. In particular, melatonin regulates the sleep-wake cycle by chemically causing drowsiness and. lowering the body temperature. Melatonin is also implicated in the regulation of mood,learning and memory, immune activity, dreaming, fertility and reproduction. Melatonin is also an effective antioxidant. Most of the actions of melatonin are mediated through the binding and activation of melatonin receptors. Individuals with autism spectrum disorders(ASD) may have lower than normal levels of melatonin. A 2008 study found that unaffected parents of individuals with ASD also have lower melatonin levels, and that the deficits. were associated with low activity of the ASMT gene, which encodes the last enzyme of melatonin synthesis. Reduced melatonin production has also been proposed as a likely factor in the significantly higher cancer rates in night workers.
Structure
Thumb
Synonyms
  1. 5-Methoxy-N-acetyltryptamine
  2. Circadin
  3. Melatol
  4. Melatonin
  5. Melatonin (synth.) standard-grade
  6. Melatonin (synth.) ultra-pure
  7. Melatonine
  8. Melovine
  9. MT6
  10. N-(2-(5-Methoxy-1H-indol-3-yl)ethyl)acetamide
  11. N-(2-(5-Methoxyindol-3-yl)ethyl)-Acetamide
  12. N-(2-(5-Methoxyindol-3-yl)ethyl)acetamide
  13. N-Acetyl-5-methoxy-tryptamine
  14. N-Acetyl-5-methoxy-tryptamine Melatonine
  15. N-Acetyl-5-methoxytryptamine
  16. N-[2-(5-Methoxy-1H-indol-3-yl)ethyl)acetamide
  17. N-[2-(5-Methoxy-1H-indol-3-yl)ethyl]-Acetamide
  18. N-[2-(5-Methoxy-1H-indol-3-yl)ethyl]acetamide
  19. N-[2-(5-Methoxyindol-3-yl)ethyl]-Acetamide
  20. N-[2-(5-Methoxyindol-3-yl)ethyl]acetamide
  21. Regulin
  22. {N-[2-(5-methoxy-1H-indol-3-yl)ethyl]-} Acetamide
  23. {N-[2-(5-methoxyindol-3-yl)ethyl]-} Acetamide
Chemical FormulaC13H16N2O2
Average Molecular Weight232.2783
Monoisotopic Molecular Weight232.121177766
IUPAC NameN-[2-(5-methoxy-1H-indol-3-yl)ethyl]acetamide
Traditional IUPAC Namemelatonin
CAS Registry Number73-31-4
SMILES
COC1=CC2=C(NC=C2CCNC(C)=O)C=C1
InChI Identifier
InChI=1S/C13H16N2O2/c1-9(16)14-6-5-10-8-15-13-4-3-11(17-2)7-12(10)13/h3-4,7-8,15H,5-6H2,1-2H3,(H,14,16)
InChI KeyDRLFMBDRBRZALE-UHFFFAOYSA-N
Chemical Taxonomy
KingdomOrganic Compounds
Super ClassAromatic Heteropolycyclic Compounds
ClassIndoles
Sub ClassTryptamines and Derivatives
Other Descriptors
  • Indole alkaloids(KEGG)
  • Indoles
  • Melatonin(KEGG)
  • Tryptamines and Derivatives
  • a small molecule(Cyc)
  • acetamides(ChEBI)
  • tryptamines(ChEBI)
Substituents
  • Alkyl Aryl Ether
  • Anisole
  • Carboxamide Group
  • Pyrrole
  • Secondary Carboxylic Acid Amide
Direct ParentSerotonins
Ontology
StatusDetected and Quantified
Origin
  • Endogenous
Biofunction
  • Component of Tryptophan metabolism
  • Electron donor
  • Enzyme co-factor
ApplicationNot Available
Cellular locations
  • Cytoplasm
Physical Properties
StateSolid
Experimental Properties
PropertyValueReference
Melting Point117 °CNot Available
Boiling PointNot AvailableNot Available
Water SolubilityNot AvailableNot Available
LogPNot AvailableNot Available
Predicted Properties
PropertyValueSource
Water Solubility0.14 g/LALOGPS
logP1.42ALOGPS
logP1.15ChemAxon
logS-3.2ALOGPS
pKa (Strongest Acidic)15.8ChemAxon
pKa (Strongest Basic)-0.94ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count2ChemAxon
Hydrogen Donor Count2ChemAxon
Polar Surface Area54.12ChemAxon
Rotatable Bond Count4ChemAxon
Refractivity66.28ChemAxon
Polarizability25.49ChemAxon
Spectra
SpectraGC-MSMS/MSLC-MS1D NMR2D NMR
Biological Properties
Cellular Locations
  • Cytoplasm
Biofluid Locations
  • Blood
  • Cerebrospinal Fluid (CSF)
  • Urine
Tissue Location
  • Adipose Tissue
  • Adrenal Cortex
  • Adrenal Gland
  • Adrenal Medulla
  • Bladder
  • Brain
  • Fibroblasts
  • Gastrointestinal Tract
  • Gonads
  • Gut
  • Intestine
  • Kidney
  • Liver
  • Nerve Cells
  • Neuron
  • Neutrophil
  • Ovary
  • Pancreas
  • Pineal Gland
  • Placenta
  • Platelet
  • Prostate
  • Skeletal
Pathways
NameSMPDB LinkKEGG Link
Tryptophan MetabolismSMP00063map00380
Normal Concentrations
BiofluidStatusValueAgeSexConditionReferenceDetails
BloodDetected and Quantified0.00019 +/- 0.00015 uMNewborn (0-30 days old)BothNormal
    • Geigy Scientific ...
details
BloodDetected and Quantified0.00006 +/- 0.000015 uMAdult (>18 years old)FemaleNormal
    • Geigy Scientific ...
details
BloodDetected and Quantified0.000063 +/- 0.000026 uMAdult (>18 years old)MaleNormal
    • Geigy Scientific ...
details
BloodDetected and Quantified0.00256 +/- 0.00168 uMInfant (0-1 year old)MaleNormal
    • Geigy Scientific ...
details
BloodDetected and Quantified0.00006 +/- 0.000015 uMNewborn (0-30 days old)MaleNormal
    • Geigy Scientific ...
details
Cerebrospinal Fluid (CSF)Detected and Quantified0.0279 (0.00-0.0558) uMAdult (>18 years old)BothNormal details
UrineDetected and Quantified0.0000033 (0.0000006-0.000006) umol/mmol creatinineAdult (>18 years old)BothNormal
    • Geigy Scientific ...
details
Abnormal Concentrations
Not Available
Associated Disorders and Diseases
Disease ReferencesNone
Associated OMIM IDsNone
DrugBank IDDB01065
DrugBank Metabolite IDNot Available
Phenol Explorer Compound IDNot Available
Phenol Explorer Metabolite IDNot Available
FoodDB IDFDB004234
KNApSAcK IDNot Available
Chemspider ID872
KEGG Compound IDC01598
BioCyc IDN-ACETYL-5-METHOXY-TRYPTAMINE
BiGG ID37965
Wikipedia LinkMelatonin
NuGOwiki LinkHMDB01389
Metagene LinkHMDB01389
METLIN ID73
PubChem Compound896
PDB IDML1
ChEBI ID16796
References
Synthesis ReferenceReddy, Gaddam Om; Sarma, Mamillapilli Ramabhadra; Prabhakar, Chebiyyam. An improved process for the preparation of melatonin. Indian (2001), 30 pp.
Material Safety Data Sheet (MSDS)Download (PDF)
General References
  1. Slominski A, Pisarchik A, Zbytek B, Tobin DJ, Kauser S, Wortsman J: Functional activity of serotoninergic and melatoninergic systems expressed in the skin. J Cell Physiol. 2003 Jul;196(1):144-53. Pubmed: 12767050
  2. Boutin JA, Audinot V, Ferry G, Delagrange P: Molecular tools to study melatonin pathways and actions. Trends Pharmacol Sci. 2005 Aug;26(8):412-9. Pubmed: 15992934
  3. Christofides J, Bridel M, Egerton M, Mackay GM, Forrest CM, Stoy N, Darlington LG, Stone TW: Blood 5-hydroxytryptamine, 5-hydroxyindoleacetic acid and melatonin levels in patients with either Huntington's disease or chronic brain injury. J Neurochem. 2006 May;97(4):1078-88. Epub 2006 Mar 29. Pubmed: 16573644
  4. Drake MJ, Mills IW, Noble JG: Melatonin pharmacotherapy for nocturia in men with benign prostatic enlargement. J Urol. 2004 Mar;171(3):1199-202. Pubmed: 14767300
  5. Lahiri DK, Chen D, Lahiri P, Rogers JT, Greig NH, Bondy S: Melatonin, metals, and gene expression: implications in aging and neurodegenerative disorders. Ann N Y Acad Sci. 2004 Dec;1035:216-30. Pubmed: 15681810
  6. Bangha E, Lauth D, Kistler GS, Elsner P: Daytime serum levels of melatonin after topical application onto the human skin. Skin Pharmacol. 1997;10(5-6):298-302. Pubmed: 9449169
  7. Bubenik GA: Localization, physiological significance and possible clinical implication of gastrointestinal melatonin. Biol Signals Recept. 2001 Nov-Dec;10(6):350-66. Pubmed: 11721091
  8. Abdel-Wahhab MA, Abdel-Galil MM, El-Lithey M: Melatonin counteracts oxidative stress in rats fed an ochratoxin A contaminated diet. J Pineal Res. 2005 Mar;38(2):130-5. Pubmed: 15683468
  9. Chen HM, Hsu JT, Chen JC, Ng CJ, Chiu DF, Chen MF: Delayed neutrophil apoptosis attenuated by melatonin in human acute pancreatitis. Pancreas. 2005 Nov;31(4):360-4. Pubmed: 16258371
  10. Fabis M, Pruszynska E, Mackowiak P: In vivo and in situ action of melatonin on insulin secretion and some metabolic implications in the rat. Pancreas. 2002 Aug;25(2):166-9. Pubmed: 12142740
  11. Messner M, Huether G, Lorf T, Ramadori G, Schworer H: Presence of melatonin in the human hepatobiliary-gastrointestinal tract. Life Sci. 2001 Jun 22;69(5):543-51. Pubmed: 11510949
  12. Nishida S: Metabolic effects of melatonin on oxidative stress and diabetes mellitus. Endocrine. 2005 Jul;27(2):131-6. Pubmed: 16217126
  13. Peschke E, Frese T, Chankiewitz E, Peschke D, Preiss U, Schneyer U, Spessert R, Muhlbauer E: Diabetic Goto Kakizaki rats as well as type 2 diabetic patients show a decreased diurnal serum melatonin level and an increased pancreatic melatonin-receptor status. J Pineal Res. 2006 Mar;40(2):135-43. Pubmed: 16441550
  14. Reiter RJ, Sainz RM, Lopez-Burillo S, Mayo JC, Manchester LC, Tan DX: Melatonin ameliorates neurologic damage and neurophysiologic deficits in experimental models of stroke. Ann N Y Acad Sci. 2003 May;993:35-47; discussion 48-53. Pubmed: 12853293
  15. Okatani Y, Wakatsuki A, Shinohara K, Kaneda C, Fukaya T: Melatonin stimulates glutathione peroxidase activity in human chorion. J Pineal Res. 2001 May;30(4):199-205. Pubmed: 11339508
  16. Bubenik GA: Gastrointestinal melatonin: localization, function, and clinical relevance. Dig Dis Sci. 2002 Oct;47(10):2336-48. Pubmed: 12395907
  17. Wurtman RJ, Ozaki Y: Physiological control of melatonin synthesis and secretion: mechanisms, generating rhythms in melatonin, methoxytryptophol, and arginine vasotocin levels and effects on the pineal of endogenous catecholamines, the estrous cycle, and environmental lighting. J Neural Transm Suppl. 1978;(13):59-70. Pubmed: 288858
  18. Kobayashi H, Kromminga A, Dunlop TW, Tychsen B, Conrad F, Suzuki N, Memezawa A, Bettermann A, Aiba S, Carlberg C, Paus R: A role of melatonin in neuroectodermal-mesodermal interactions: the hair follicle synthesizes melatonin and expresses functional melatonin receptors. FASEB J. 2005 Oct;19(12):1710-2. Epub 2005 Jul 19. Pubmed: 16030176
  19. Johe PD, Osterud B: The in vivo effect of melatonin on cellular activation processes in human blood during strenuous physical exercise. J Pineal Res. 2005 Oct;39(3):324-30. Pubmed: 16150115
  20. Paakkonen T, Makinen TM, Leppaluoto J, Vakkuri O, Rintamaki H, Palinkas LA, Hassi J: Urinary melatonin: a noninvasive method to follow human pineal function as studied in three experimental conditions. J Pineal Res. 2006 Mar;40(2):110-5. Pubmed: 16441547
  21. Atkinson G, Holder A, Robertson C, Gant N, Drust B, Reilly T, Waterhouse J: Effects of melatonin on the thermoregulatory responses to intermittent exercise. J Pineal Res. 2005 Nov;39(4):353-9. Pubmed: 16207290
  22. Hattori A, Migitaka H, Iigo M, Itoh M, Yamamoto K, Ohtani-Kaneko R, Hara M, Suzuki T, Reiter RJ: Identification of melatonin in plants and its effects on plasma melatonin levels and binding to melatonin receptors in vertebrates. Biochem Mol Biol Int. 1995 Mar;35(3):627-34. Pubmed: 7773197
  23. Reiter RJ, Acuna-Castroviejo D, Tan DX, Burkhardt S: Free radical-mediated molecular damage. Mechanisms for the protective actions of melatonin in the central nervous system. Ann N Y Acad Sci. 2001 Jun;939:200-15. Pubmed: 11462772
  24. Caniato R, Filippini R, Piovan A, Puricelli L, Borsarini A, Cappelletti EM: Melatonin in plants. Adv Exp Med Biol. 2003;527:593-7. Pubmed: 15206778
  25. Hardeland R: Antioxidative protection by melatonin: multiplicity of mechanisms from radical detoxification to radical avoidance. Endocrine. 2005 Jul;27(2):119-30. Pubmed: 16217125
  26. Ma X, Chen C, Krausz KW, Idle JR, Gonzalez FJ: A metabolomic perspective of melatonin metabolism in the mouse. Endocrinology. 2008 Apr;149(4):1869-79. doi: 10.1210/en.2007-1412. Epub 2008 Jan 10. Pubmed: 18187545

Enzymes

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
References
  1. Minneman KP, Wurtman RJ: The pharmacology of the pineal gland. Annu Rev Pharmacol Toxicol. 1976;16:33-51. Pubmed: 180879
General function:
Involved in electron carrier activity
Specific function:
The enzyme apparently serves as a quinone reductase in connection with conjugation reactions of hydroquinones involved in detoxification pathways as well as in biosynthetic processes such as the vitamin K-dependent gamma-carboxylation of glutamate residues in prothrombin synthesis.
Gene Name:
NQO2
Uniprot ID:
P16083
Molecular weight:
25918.4
References
  1. Radogna F, Paternoster L, De Nicola M, Cerella C, Ammendola S, Bedini A, Tarzia G, Aquilano K, Ciriolo M, Ghibelli L: Rapid and transient stimulation of intracellular reactive oxygen species by melatonin in normal and tumor leukocytes. Toxicol Appl Pharmacol. 2009 Aug 15;239(1):37-45. Epub 2009 May 19. Pubmed: 19463840
General function:
Involved in peroxidase activity
Specific function:
Part of the host defense system of polymorphonuclear leukocytes. It is responsible for microbicidal activity against a wide range of organisms. In the stimulated PMN, MPO catalyzes the production of hypohalous acids, primarily hypochlorous acid in physiologic situations, and other toxic intermediates that greatly enhance PMN microbicidal activity.
Gene Name:
MPO
Uniprot ID:
P05164
Molecular weight:
83867.71
References
  1. Ferry G, Ubeaud C, Lambert PH, Bertin S, Coge F, Chomarat P, Delagrange P, Serkiz B, Bouchet JP, Truscott RJ, Boutin JA: Molecular evidence that melatonin is enzymatically oxidized in a different manner than tryptophan: investigations with both indoleamine 2,3-dioxygenase and myeloperoxidase. Biochem J. 2005 May 15;388(Pt 1):205-15. Pubmed: 15636586
  2. Galijasevic S, Abdulhamid I, Abu-Soud HM: Melatonin is a potent inhibitor for myeloperoxidase. Biochemistry. 2008 Feb 26;47(8):2668-77. Epub 2008 Feb 1. Pubmed: 18237195
General function:
Involved in peroxidase activity
Specific function:
Mediates tyrosine nitration of secondary granule proteins in mature resting eosinophils. Shows significant inhibitory activity towards Mycobacterium tuberculosis H37Rv by inducing bacterial fragmentation and lysis.
Gene Name:
EPX
Uniprot ID:
P11678
Molecular weight:
81039.5
References
  1. Lu T, Galijasevic S, Abdulhamid I, Abu-Soud HM: Analysis of the mechanism by which melatonin inhibits human eosinophil peroxidase. Br J Pharmacol. 2008 Jul;154(6):1308-17. Epub 2008 Jun 2. Pubmed: 18516076
General function:
Involved in heme binding
Specific function:
Catalyzes the cleavage of the pyrrol ring of tryptophan and incorporates both atoms of a molecule of oxygen.
Gene Name:
IDO1
Uniprot ID:
P14902
Molecular weight:
45325.89
Reactions
Melatonin + Oxygen → Acetyl-N-formyl-5-methoxykynurenaminedetails
References
  1. Ferry G, Ubeaud C, Lambert PH, Bertin S, Coge F, Chomarat P, Delagrange P, Serkiz B, Bouchet JP, Truscott RJ, Boutin JA: Molecular evidence that melatonin is enzymatically oxidized in a different manner than tryptophan: investigations with both indoleamine 2,3-dioxygenase and myeloperoxidase. Biochem J. 2005 May 15;388(Pt 1):205-15. Pubmed: 15636586
General function:
Involved in monooxygenase activity
Specific function:
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics. This enzyme contributes to the wide pharmacokinetics variability of the metabolism of drugs such as S-warfarin, diclofenac, phenytoin, tolbutamide and losartan.
Gene Name:
CYP2C9
Uniprot ID:
P11712
Molecular weight:
55627.365
References
  1. Mo SL, Zhou ZW, Yang LP, Wei MQ, Zhou SF: New insights into the structural features and functional relevance of human cytochrome P450 2C9. Part I. Curr Drug Metab. 2009 Dec;10(10):1075-126. Pubmed: 20167001
General function:
Involved in monooxygenase activity
Specific function:
Responsible for the metabolism of a number of therapeutic agents such as the anticonvulsant drug S-mephenytoin, omeprazole, proguanil, certain barbiturates, diazepam, propranolol, citalopram and imipramine.
Gene Name:
CYP2C19
Uniprot ID:
P33261
Molecular weight:
55944.565
References
  1. Huuhka K, Riutta A, Haataja R, Ylitalo P, Leinonen E: The effect of CYP2C19 substrate on the metabolism of melatonin in the elderly: A randomized, double-blind, placebo-controlled study. Methods Find Exp Clin Pharmacol. 2006 Sep;28(7):447-50. Pubmed: 17003850
  2. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. Epub 2009 Nov 24. Pubmed: 19934256
General function:
Involved in monooxygenase activity
Specific function:
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics. Participates in the metabolism of an as-yet-unknown biologically active molecule that is a participant in eye development.
Gene Name:
CYP1B1
Uniprot ID:
Q16678
Molecular weight:
60845.33
References
  1. Chang TK, Chen J, Yang G, Yeung EY: Inhibition of procarcinogen-bioactivating human CYP1A1, CYP1A2 and CYP1B1 enzymes by melatonin. J Pineal Res. 2010 Jan;48(1):55-64. Epub 2009 Nov 16. Pubmed: 19919601
  2. 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
  3. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. Epub 2009 Nov 24. Pubmed: 19934256
General function:
Involved in monooxygenase activity
Specific function:
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics.
Gene Name:
CYP1A1
Uniprot ID:
P04798
Molecular weight:
58164.815
References
  1. Chang TK, Chen J, Yang G, Yeung EY: Inhibition of procarcinogen-bioactivating human CYP1A1, CYP1A2 and CYP1B1 enzymes by melatonin. J Pineal Res. 2010 Jan;48(1):55-64. Epub 2009 Nov 16. Pubmed: 19919601
  2. 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
  3. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. Epub 2009 Nov 24. Pubmed: 19934256
General function:
Involved in monooxygenase activity
Specific function:
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics. Most active in catalyzing 2-hydroxylation. Caffeine is metabolized primarily by cytochrome CYP1A2 in the liver through an initial N3-demethylation. Also acts in the metabolism of aflatoxin B1 and acetaminophen. Participates in the bioactivation of carcinogenic aromatic and heterocyclic amines. Catalizes the N-hydroxylation of heterocyclic amines and the O-deethylation of phenacetin.
Gene Name:
CYP1A2
Uniprot ID:
P05177
Molecular weight:
58406.915
References
  1. Chang TK, Chen J, Yang G, Yeung EY: Inhibition of procarcinogen-bioactivating human CYP1A1, CYP1A2 and CYP1B1 enzymes by melatonin. J Pineal Res. 2010 Jan;48(1):55-64. Epub 2009 Nov 16. Pubmed: 19919601
  2. 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
  3. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. Epub 2009 Nov 24. Pubmed: 19934256
  4. Turpeinen M, Uusitalo J, Jalonen J, Pelkonen O: Multiple P450 substrates in a single run: rapid and comprehensive in vitro interaction assay. Eur J Pharm Sci. 2005 Jan;24(1):123-32. Pubmed: 15626586
General function:
Involved in monooxygenase activity
Specific function:
Catalyzes the formation of aromatic C18 estrogens from C19 androgens.
Gene Name:
CYP19A1
Uniprot ID:
P11511
Molecular weight:
57882.48
References
  1. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. Epub 2009 Nov 24. Pubmed: 19934256
General function:
Involved in calcium ion binding
Specific function:
Calmodulin mediates the control of a large number of enzymes and other proteins by Ca(2+). Among the enzymes to be stimulated by the calmodulin-Ca(2+) complex are a number of protein kinases and phosphatases. Together with CEP110 and centrin, is involved in a genetic pathway that regulates the centrosome cycle and progression through cytokinesis
Gene Name:
CALM1
Uniprot ID:
P62158
Molecular weight:
16837.5
References
  1. del Rio B, Garcia Pedrero JM, Martinez-Campa C, Zuazua P, Lazo PS, Ramos S: Melatonin, an endogenous-specific inhibitor of estrogen receptor alpha via calmodulin. J Biol Chem. 2004 Sep 10;279(37):38294-302. Epub 2004 Jun 30. Pubmed: 15229223
  2. Radogna F, Paternoster L, De Nicola M, Cerella C, Ammendola S, Bedini A, Tarzia G, Aquilano K, Ciriolo M, Ghibelli L: Rapid and transient stimulation of intracellular reactive oxygen species by melatonin in normal and tumor leukocytes. Toxicol Appl Pharmacol. 2009 Aug 15;239(1):37-45. Epub 2009 May 19. Pubmed: 19463840
General function:
Involved in sequence-specific DNA binding transcription factor activity
Specific function:
Nuclear hormone receptor. The steroid hormones and their receptors are involved in the regulation of eukaryotic gene expression and affect cellular proliferation and differentiation in target tissues. Can activate the transcriptional activity of TFF1
Gene Name:
ESR1
Uniprot ID:
P03372
Molecular weight:
66215.4
References
  1. del Rio B, Garcia Pedrero JM, Martinez-Campa C, Zuazua P, Lazo PS, Ramos S: Melatonin, an endogenous-specific inhibitor of estrogen receptor alpha via calmodulin. J Biol Chem. 2004 Sep 10;279(37):38294-302. Epub 2004 Jun 30. Pubmed: 15229223
  2. Yoo YM, Jeung EB: Melatonin-induced estrogen receptor alpha-mediated calbindin-D9k expression plays a role in H2O2-mediated cell death in rat pituitary GH3 cells. J Pineal Res. 2009 Nov;47(4):301-7. Epub 2009 Oct 1. Pubmed: 19796047
General function:
Involved in heme binding
Specific function:
Catalyzes the first and rate-limiting step in the kynurenine pathway of tryptophan catabolism.
Gene Name:
IDO2
Uniprot ID:
Q6ZQW0
Molecular weight:
47074.745
Reactions
Melatonin + Oxygen → Acetyl-N-formyl-5-methoxykynurenaminedetails
General function:
Involved in calcium ion binding
Specific function:
Molecular calcium-binding chaperone promoting folding, oligomeric assembly and quality control in the ER via the calreticulin/calnexin cycle. This lectin interacts transiently with almost all of the monoglucosylated glycoproteins that are synthesized in the ER. Interacts with the DNA-binding domain of NR3C1 and mediates its nuclear export
Gene Name:
CALR
Uniprot ID:
P27797
Molecular weight:
48141.2
References
  1. Hardeland R: Melatonin: signaling mechanisms of a pleiotropic agent. Biofactors. 2009 Mar-Apr;35(2):183-92. Pubmed: 19449447
  2. Macias M, Escames G, Leon J, Coto A, Sbihi Y, Osuna A, Acuna-Castroviejo D: Calreticulin-melatonin. An unexpected relationship. Eur J Biochem. 2003 Mar;270(5):832-40. Pubmed: 12603316
General function:
Involved in G-protein coupled receptor protein signaling pathway
Specific function:
High affinity receptor for melatonin. Likely to mediates the reproductive and circadian actions of melatonin. The activity of this receptor is mediated by pertussis toxin sensitive G proteins that inhibit adenylate cyclase activity
Gene Name:
MTNR1A
Uniprot ID:
P48039
Molecular weight:
39374.3
References
  1. Radogna F, Paternoster L, De Nicola M, Cerella C, Ammendola S, Bedini A, Tarzia G, Aquilano K, Ciriolo M, Ghibelli L: Rapid and transient stimulation of intracellular reactive oxygen species by melatonin in normal and tumor leukocytes. Toxicol Appl Pharmacol. 2009 Aug 15;239(1):37-45. Epub 2009 May 19. Pubmed: 19463840
  2. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. Pubmed: 11752352
  3. Boutin JA, Audinot V, Ferry G, Delagrange P: Molecular tools to study melatonin pathways and actions. Trends Pharmacol Sci. 2005 Aug;26(8):412-9. Pubmed: 15992934
  4. Hardeland R: Melatonin: signaling mechanisms of a pleiotropic agent. Biofactors. 2009 Mar-Apr;35(2):183-92. Pubmed: 19449447
  5. Srinivasan V, Singh J, Pandi-Perumal SR, Brown GM, Spence DW, Cardinali DP: Jet lag, circadian rhythm sleep disturbances, and depression: the role of melatonin and its analogs. Adv Ther. 2010 Nov;27(11):796-813. Epub 2010 Sep 6. Pubmed: 20827520
  6. Carocci A, Catalano A, Lovece A, Lentini G, Duranti A, Lucini V, Pannacci M, Scaglione F, Franchini C: Design, synthesis, and pharmacological effects of structurally simple ligands for MT(1) and MT(2) melatonin receptors. Bioorg Med Chem. 2010 Sep 1;18(17):6496-511. Epub 2010 Jul 3. Pubmed: 20674373
  7. Prendergast BJ: MT1 melatonin receptors mediate somatic, behavioral, and reproductive neuroendocrine responses to photoperiod and melatonin in Siberian hamsters (Phodopus sungorus). Endocrinology. 2010 Feb;151(2):714-21. Epub 2009 Dec 4. Pubmed: 19966183
General function:
Involved in G-protein coupled receptor protein signaling pathway
Specific function:
High affinity receptor for melatonin. Likely to mediates the reproductive and circadian actions of melatonin. The activity of this receptor is mediated by pertussis toxin sensitive G proteins that inhibit adenylate cyclase activity
Gene Name:
MTNR1B
Uniprot ID:
P49286
Molecular weight:
40187.9
References
  1. Radogna F, Paternoster L, De Nicola M, Cerella C, Ammendola S, Bedini A, Tarzia G, Aquilano K, Ciriolo M, Ghibelli L: Rapid and transient stimulation of intracellular reactive oxygen species by melatonin in normal and tumor leukocytes. Toxicol Appl Pharmacol. 2009 Aug 15;239(1):37-45. Epub 2009 May 19. Pubmed: 19463840
  2. Boutin JA, Audinot V, Ferry G, Delagrange P: Molecular tools to study melatonin pathways and actions. Trends Pharmacol Sci. 2005 Aug;26(8):412-9. Pubmed: 15992934
  3. Hardeland R: Melatonin: signaling mechanisms of a pleiotropic agent. Biofactors. 2009 Mar-Apr;35(2):183-92. Pubmed: 19449447
  4. Srinivasan V, Singh J, Pandi-Perumal SR, Brown GM, Spence DW, Cardinali DP: Jet lag, circadian rhythm sleep disturbances, and depression: the role of melatonin and its analogs. Adv Ther. 2010 Nov;27(11):796-813. Epub 2010 Sep 6. Pubmed: 20827520
  5. Carocci A, Catalano A, Lovece A, Lentini G, Duranti A, Lucini V, Pannacci M, Scaglione F, Franchini C: Design, synthesis, and pharmacological effects of structurally simple ligands for MT(1) and MT(2) melatonin receptors. Bioorg Med Chem. 2010 Sep 1;18(17):6496-511. Epub 2010 Jul 3. Pubmed: 20674373
  6. Prendergast BJ: MT1 melatonin receptors mediate somatic, behavioral, and reproductive neuroendocrine responses to photoperiod and melatonin in Siberian hamsters (Phodopus sungorus). Endocrinology. 2010 Feb;151(2):714-21. Epub 2009 Dec 4. Pubmed: 19966183
General function:
Involved in sequence-specific DNA binding transcription factor activity
Specific function:
Orphan nuclear receptor required for normal postnatal development of rod and cone photoreceptor cells. Regulates transcription of OPN1SW in cone photoreceptor cells by binding the sequence 5'-AGGTCA-3' in the OPN1SW promoter
Gene Name:
RORB
Uniprot ID:
Q92753
Molecular weight:
53219.4
References
  1. Becker-Andre M, Wiesenberg I, Schaeren-Wiemers N, Andre E, Missbach M, Saurat JH, Carlberg C: Pineal gland hormone melatonin binds and activates an orphan of the nuclear receptor superfamily. J Biol Chem. 1994 Nov 18;269(46):28531-4. Pubmed: 7961794