If an enzyme name is shown in bold, there is experimental evidence for this enzymatic activity.
Locations of Mapped Genes:
|Superclasses:||Degradation/Utilization/Assimilation → Hormones Degradation → Melatonin Degradation|
The indoleamine melatonin is a vertebrate hormone secreted by the pineal gland. It is involved in regulation of circadian and seasonal rhythms. melatonin also has immunomodulatory, anti-inflammatory and antioxidant properties. In addition to the pineal gland it is synthesized in many vertebrate cells and tissues (see pathway serotonin and melatonin biosynthesis). It is ubiquitously present in cells and body fluids due to its amphiphilic properties that allow it to cross membranes. Mitochondria have the highest intracellular concentration of melatonin [Semak05]. Its functional groups allow both specific receptor binding and a role in oxidation chemistry. melatonin is also found in invertebrates [Hardeland03], protozoa [Kohidai03], plants [Van01a], fungi [Hardeland03] and bacteria [Tilden97] although its function in many cases remains incompletely defined. melatonin is also used as a human dietary supplement. In vertebrates, endogenous or ingested melatonin is catabolized several ways in different tissues (see below and pathways melatonin degradation I and melatonin degradation III). Reviewed in [Hardeland06, Hardeland08].
The enzymatic pathways of melatonin degradation are shown in this pathway and pathways melatonin degradation I and melatonin degradation III. Melatonin can also be degraded by nonenzymatic pathways involving melatonin radical species, reactive oxygen species, reactive nitrogen species, or ultraviolet B radiation. It can also be degraded by nonenzymatic reactions involving oxoferryl hemoglobin, or hemin. These nonenzymatic reactions are not shown here, but are shown in [Hardeland08, Slominski08, Tan07, Fischer06].
About This Pathway
Melatonin can be degraded by by deacetylation to 5-methoxytryptamine, followed by oxidative deamination by monoamine oxidase A to 5-methoxyindoleacetaldehyde and subsequent dehydrogenation of this compound by an aldehyde dehydrogenase to the acid 5-methoxyindole acetate. 5-methoxyindoleacetaldehyde may also be reduced to the alchohol 5-methoxytryptophol by an alcohol dehydrogenase. Bioactive derivatives of this alcohol such as its O-acetyl derivative [Smith80b], or the β-carboline pinoline, can also be formed in some tissues (in [Hardeland08]) (not shown). This pathway has been shown in mammalian skin [Slominski05, Slominski05a]. Deacetylation is also a minor pathway in mammalian liver (in [Grace93]). In addition, some of these metabolites have been found in protozoa, algae and yeast (in [Hardeland08]).
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Grace94: Grace MS, Besharse JC (1994). "Melatonin deacetylase activity in the pineal gland and brain of the lizards Anolis carolinensis and Sceloporus jarrovi." Neuroscience 62(2);615-23. PMID: 7530349
Kohidai03: Kohidai L, Vakkuri O, Keresztesi M, Leppaluoto J, Csaba G (2003). "Induction of melatonin synthesis in Tetrahymena pyriformis by hormonal imprinting--a unicellular "factory" of the indoleamine." Cell Mol Biol (Noisy-le-grand) 49(4);521-4. PMID: 12899443
Slominski05: Slominski A, Fischer TW, Zmijewski MA, Wortsman J, Semak I, Zbytek B, Slominski RM, Tobin DJ (2005). "On the role of melatonin in skin physiology and pathology." Endocrine 27(2);137-48. PMID: 16217127
Smith80b: Smith I, Francis P, Leone RM, Mullen PE (1980). "Identification of O-acetyl-5-methoxytryptophenol in the pineal gland by gas chromatography-mass spectrometry." Biochem J 185(2);537-40. PMID: 7396831
Tan07: Tan DX, Manchester LC, Terron MP, Flores LJ, Reiter RJ (2007). "One molecule, many derivatives: a never-ending interaction of melatonin with reactive oxygen and nitrogen species?." J Pineal Res 42(1);28-42. PMID: 17198536
Tilden97: Tilden AR, Becker MA, Amma LL, Arciniega J, McGaw AK (1997). "Melatonin production in an aerobic photosynthetic bacterium: an evolutionarily early association with darkness." J Pineal Res 22(2);102-6. PMID: 9181522
Bach88: Bach AW, Lan NC, Johnson DL, Abell CW, Bembenek ME, Kwan SW, Seeburg PH, Shih JC (1988). "cDNA cloning of human liver monoamine oxidase A and B: molecular basis of differences in enzymatic properties." Proc Natl Acad Sci U S A 85(13);4934-8. PMID: 3387449
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Brunner93: Brunner HG, Nelen M, Breakefield XO, Ropers HH, van Oost BA (1993). "Abnormal behavior associated with a point mutation in the structural gene for monoamine oxidase A." Science 262(5133);578-80. PMID: 8211186
Chen91a: Chen ZY, Hotamisligil GS, Huang JK, Wen L, Ezzeddine D, Aydin-Muderrisoglu N, Powell JF, Huang RH, Breakefield XO, Craig I (1991). "Structure of the human gene for monoamine oxidase type A." Nucleic Acids Res 19(16);4537-41. PMID: 1886775
De05: De Colibus L, Li M, Binda C, Lustig A, Edmondson DE, Mattevi A (2005). "Three-dimensional structure of human monoamine oxidase A (MAO A): relation to the structures of rat MAO A and human MAO B." Proc Natl Acad Sci U S A 102(36);12684-9. PMID: 16129825
Grimsby91: Grimsby J, Chen K, Wang LJ, Lan NC, Shih JC (1991). "Human monoamine oxidase A and B genes exhibit identical exon-intron organization." Proc Natl Acad Sci U S A 88(9);3637-41. PMID: 2023912
Lan89: Lan NC, Heinzmann C, Gal A, Klisak I, Orth U, Lai E, Grimsby J, Sparkes RS, Mohandas T, Shih JC (1989). "Human monoamine oxidase A and B genes map to Xp 11.23 and are deleted in a patient with Norrie disease." Genomics 4(4);552-9. PMID: 2744764
Li02d: Li M, Hubalek F, Newton-Vinson P, Edmondson DE (2002). "High-level expression of human liver monoamine oxidase A in Pichia pastoris: comparison with the enzyme expressed in Saccharomyces cerevisiae." Protein Expr Purif 24(1);152-62. PMID: 11812236
Manor02: Manor I, Tyano S, Mel E, Eisenberg J, Bachner-Melman R, Kotler M, Ebstein RP (2002). "Family-based and association studies of monoamine oxidase A and attention deficit hyperactivity disorder (ADHD): preferential transmission of the long promoter-region repeat and its association with impaired performance on a continuous performance test (TOVA)." Mol Psychiatry 7(6);626-32. PMID: 12140786
Schnaitman67: Schnaitman C, Erwin VG, Greenawalt JW (1967). "The submitochondrial localization of monoamine oxidase. An enzymatic marker for the outer membrane of rat liver mitochondria." J Cell Biol 32(3);719-35. PMID: 4291912
Weyler90: Weyler W, Titlow CC, Salach JI (1990). "Catalytically active monoamine oxidase type A from human liver expressed in Saccharomyces cerevisiae contains covalent FAD." Biochem Biophys Res Commun 173(3);1205-11. PMID: 2125217
Zhou95a: Zhou BP, Lewis DA, Kwan SW, Kirksey TJ, Abell CW (1995). "Mutagenesis at a highly conserved tyrosine in monoamine oxidase B affects FAD incorporation and catalytic activity." Biochemistry 34(29);9526-31. PMID: 7626622
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