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 [Van01], 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 [Smith80], 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]).
Created 07-Dec-2009 by SRI International
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Smith80: 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
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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
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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
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