Melatonin metabolism and effects (WP3298)
Homo sapiens
Melatonin is an important regulator of circadian rythmus and influences also insulin secretion, immune function, retinal function and neuroprotection. The synthesis starts with the amino acid tryptophan which is catalyzed to serotonin. AANAT and ASMT catalyze the reaction to N-acetylserotonin and melatonin, respectively. Melatonin is mainly discarded by the liver enzyme CYP1A2 but other enzymes from the cytochrome family are also known to metabolize melatonin. Recent investigation show e.g. that melatonin plays an important role in colon cancer growth. Proteins on this pathway have targeted assays available via the [https://assays.cancer.gov/available_assays?wp_id=WP3298 CPTAC Assay Portal]
Authors
Friederike Ehrhart , Chris Evelo , Martina Summer-Kutmon , Egon Willighagen , Kristina Hanspers , Alex Pico , Justin Gerrardz , Marvin Martens , and Eric WeitzActivity
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Cited In
- Identification of biomarkers and pathways for the SARS-CoV-2 infections that make complexities in pulmonary arterial hypertension patients (2021).
- Citalopram-induced pathways regulation and tentative treatment-outcome-predicting biomarkers in lymphoblastoid cell lines from depression patients (2020).
- Human Monocytes Exposed to SARS-CoV-2 Display Features of Innate Immune Memory Producing High Levels of CXCL10 upon Restimulation (2023).
- Methylation analysis by targeted bisulfite sequencing in large for gestational age (LGA) newborns: the LARGAN cohort (2024).
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Organisms
Homo sapiensCommunities
Annotations
Disease Ontology
sleep disorder cancer developmental disorder of mental healthPathway Ontology
hormone signaling pathway| Label | Type | Compact URI | Comment |
|---|---|---|---|
| N-Acetylserotonin | Metabolite | chebi:17697 | |
| Serotonin | Metabolite | chebi:28790 | |
| Lipopolysaccharide | Metabolite | chebi:16412 | |
| 5-Hydroxyindoleacetic acid | Metabolite | chebi:27823 | |
| free radicals | Metabolite | chebi:26519 | |
| Pinoline | Metabolite | pubchem.compound:1868 | |
| 5-Methoxytryptamine | Metabolite | chebi:2089 | 0-methylserotonin |
| Melatonin | Metabolite | chebi:16796 | |
| cyclic 6-hydroxymelatonin | Metabolite | hmdb:HMDB0060810 | |
| Ethinhyloestradiol | Metabolite | pubchem.compound:5991 | |
| 6-Sulfatoxymelatonin | Metabolite | hmdb:HMDB0041815 | |
| cAMP | Metabolite | chebi:17489 | |
| N,N-Dimethyltryptamine | Metabolite | chebi:28969 | |
| 5-methoxypsoralen | Metabolite | pubchem.compound:2355 | |
| Noradrenaline | Metabolite | chebi:33569 | |
| 6-Hydroxymelatonin | Metabolite | chebi:2198 | |
| Bufotenin | Metabolite | chebi:3210 | |
| cyclic 3-hydroxymelatonin | Metabolite | hmdb:HMDB0060069 | |
| MAP2 | GeneProduct | ensembl:ENSG00000078018 | |
| MTNR1B | GeneProduct | ensembl:ENSG00000134640 | |
| SULT1A1 | GeneProduct | ensembl:ENSG00000196502 | |
| EDN1 | GeneProduct | ensembl:ENSG00000078401 | |
| CAM | GeneProduct | ensembl:ENSG00000198668 | calmodulin 1, CALM1 |
| CYP1B1 | GeneProduct | ensembl:ENSG00000138061 | Low expression in liver, high expression in (fetal) brain and kidney |
| ACHE | GeneProduct | ensembl:ENSG00000087085 | AAA (aryl-acylamidase) is a subfunction of ACHE |
| CaMK2 | GeneProduct | ensembl:ENSG00000070808 | |
| ARNTL | GeneProduct | ensembl:ENSG00000133794 | |
| CYP2D6 | GeneProduct | ensembl:ENSG00000100197 | proven only for rat |
| TRAF6 | GeneProduct | ensembl:ENSG00000175104 | |
| IRAK1 | GeneProduct | ensembl:ENSG00000184216 | |
| PER2 | GeneProduct | ensembl:ENSG00000132326 | |
| MTNR1A | GeneProduct | ensembl:ENSG00000168412 | |
| CLOCK | GeneProduct | ensembl:ENSG00000134852 | |
| PKC | GeneProduct | ensembl:ENSG00000154229 | PCK - alpha (literature does not give the exact subclass of PCK) |
| AANAT | GeneProduct | ensembl:ENSG00000129673 | |
| GSK3B | GeneProduct | ensembl:ENSG00000082701 | |
| SIRT1 | GeneProduct | ensembl:ENSG00000096717 | |
| ADRB | GeneProduct | ensembl:ENSG00000043591 | |
| NFKB1 | GeneProduct | ensembl:ENSG00000109320 | |
| FOXO1 | GeneProduct | ensembl:ENSG00000150907 | |
| CYP1A1 | GeneProduct | ensembl:ENSG00000140465 | |
| PER3 | GeneProduct | ensembl:ENSG00000049246 | |
| ECE-1 | GeneProduct | ensembl:ENSG00000117298 | |
| APOE | GeneProduct | uniprot:P02649 | |
| PER1 | GeneProduct | ensembl:ENSG00000179094 | |
| CYP1A2 | GeneProduct | ensembl:ENSG00000140505 | Synonym CP12, P3-450Main melatonin hydroxylating enzyme |
| ASMT | GeneProduct | ensembl:ENSG00000196433 | |
| CYP2C19 | GeneProduct | ensembl:ENSG00000165841 | |
| CRY2 | GeneProduct | ensembl:ENSG00000121671 | |
| CRY1 | GeneProduct | ensembl:ENSG00000008405 | |
| Clock | Protein | ensembl:ENSP00000426983 | |
| Cry | Protein | ensembl:ENSP00000008527 | |
| CSNK1D | Protein | ensembl:ENSG00000141551 | |
| MAOA | Protein | ensembl:ENSG00000189221 | |
| Arntl | Protein | ensembl:ENSP00000374357 | |
| Per | Protein | ensembl:ENSP00000314420 | |
| CSNK1E | Protein | ensembl:ENSG00000213923 | |
| AANAT | Protein | ensembl:ENSP00000250615 |
References
- Regeneration of serotonin from 5-methoxytryptamine by polymorphic human CYP2D6. Yu AM, Idle JR, Byrd LG, Krausz KW, Küpfer A, Gonzalez FJ. Pharmacogenetics. 2003 Mar;13(3):173–81. PubMed Europe PMC Scholia
- Metabolism of melatonin by human cytochromes p450. Ma X, Idle JR, Krausz KW, Gonzalez FJ. Drug Metab Dispos. 2005 Apr;33(4):489–94. PubMed Europe PMC Scholia
- Mechanisms regulating melatonin synthesis in the mammalian pineal organ. Schomerus C, Korf HW. Ann N Y Acad Sci. 2005 Dec;1057:372–83. PubMed Europe PMC Scholia
- Apolipoprotein E influences melatonin biosynthesis by regulating NAT and MAOA expression in C6 cells. Liu YJ, Meng FT, Wang LL, Zhang LF, Cheng XP, Zhou JN. J Pineal Res. 2012 May;52(4):397–402. PubMed Europe PMC Scholia
- Melatonin reduces endothelin-1 expression and secretion in colon cancer cells through the inactivation of FoxO-1 and NF-κβ. León J, Casado J, Jiménez Ruiz SM, Zurita MS, González-Puga C, Rejón JD, et al. J Pineal Res. 2014 May;56(4):415–26. PubMed Europe PMC Scholia
- Potential drug interactions with melatonin. Papagiannidou E, Skene DJ, Ioannides C. Physiol Behav. 2014 May 28;131:17–24. PubMed Europe PMC Scholia
- Genetic variation in melatonin pathway enzymes in children with autism spectrum disorder and comorbid sleep onset delay. Veatch OJ, Pendergast JS, Allen MJ, Leu RM, Johnson CH, Elsea SH, et al. J Autism Dev Disord. 2015 Jan;45(1):100–10. PubMed Europe PMC Scholia
- Melatonin stimulates dendrite formation and complexity in the hilar zone of the rat hippocampus: participation of the Ca++/Calmodulin complex. Domínguez-Alonso A, Valdés-Tovar M, Solís-Chagoyán H, Benítez-King G. Int J Mol Sci. 2015 Jan 16;16(1):1907–27. PubMed Europe PMC Scholia
- Sulfation of melatonin: enzymatic characterization, differences of organs, species and genders, and bioactivity variation. Tian X, Huo X, Dong P, Wu B, Wang X, Wang C, et al. Biochem Pharmacol. 2015 Apr 15;94(4):282–96. PubMed Europe PMC Scholia
- Melatonin modulates neonatal brain inflammation through endoplasmic reticulum stress, autophagy, and miR-34a/silent information regulator 1 pathway. Carloni S, Favrais G, Saliba E, Albertini MC, Chalon S, Longini M, et al. J Pineal Res. 2016 Oct;61(3):370–80. PubMed Europe PMC Scholia