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]bb1b83c94calmodulin 1, CALM1Low expression in liver, high expression in (fetal) brain and kidneydb4AAA (aryl-acylamidase) is a subfunction of ACHEdd7afbproven only for ratdd70-methylserotoninc50PCK - alpha (literature does not give the exact subclass of PCK)ed3c50ed3db4b4bafbSynonym CP12, P3-450Main melatonin hydroxylating enzymec05db4db4c50sleep disorderDOID:535Human Disease Ontologyhormone signaling pathwayPW:0000465Pathway OntologycancerDOID:162Human Disease Ontologydevelopmental disorder of mental healthDOID:0060037Human Disease Ontology25738837PubMedSulfation of melatonin: enzymatic characterization, differences of organs, species and genders, and bioactivity variation.Biochem Pharmacol2015Tian XHuo XDong PWu BWang XWang CLiu KMa X25603176PubMedMelatonin stimulates dendrite formation and complexity in the hilar zone of the rat hippocampus: participation of the Ca++/Calmodulin complex.Int J Mol Sci2015Domínguez-Alonso AValdés-Tovar MSolís-Chagoyán HBenítez-King G24628039PubMedMelatonin reduces endothelin-1 expression and secretion in colon cancer cells through the inactivation of FoxO-1 and NF-κβJ Pineal Res. 2014 May;56(4):415-26.2014León JCasado JJiménez Ruiz SMZurita MSGonzález-Puga CRejón JDGila AMuñoz de Rueda PPavón EJReiter RJRuiz-Extremera ASalmerón J.15616152PubMedMetabolism of melatonin by human cytochromes p450.Drug Metab Dispos2005Ma XIdle JRKrausz KWGonzalez FJ12618595PubMedRegeneration of serotonin from 5-methoxytryptamine by polymorphic human CYP2D6Pharmacogenetics. 2003 Mar;13(3):173-81.2003Yu AMIdle JRByrd LGKrausz KWKüpfer AGonzalez FJ.22225631PubMedApolipoprotein E influences melatonin biosynthesis by regulating NAT and MAOA expression in C6 cells.J Pineal Res2012Liu YJMeng FTWang LLZhang LFCheng XPZhou JN27441728PubMedMelatonin modulates neonatal brain inflammation through ER stress, autophagy and miR-34a/SIRT1 pathway.J Pineal Res2016Carloni SFavrais GSaliba EAlbertini MCChalon SLongini MGressens PBuonocore GBalduini W24732412PubMedPotential drug interactions with melatonin.Physiol Behav2014Papagiannidou ESkene DJIoannides C16399907PubMedMechanisms regulating melatonin synthesis in the mammalian pineal organ.Ann N Y Acad Sci2005Schomerus CKorf HW25059483PubMedGenetic variation in melatonin pathway enzymes in children with autism spectrum disorder and comorbid sleep onset delay.J Autism Dev Disord2015Veatch OJPendergast JSAllen MJLeu RMJohnson CHElsea SHMalow BA