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MetaCyc Pathway: melatonin degradation II

Enzyme View:

This view shows enzymes only for those organisms listed below, in the list of taxa known to possess the pathway. If an enzyme name is shown in bold, there is experimental evidence for this enzymatic activity.

Superclasses: Degradation/Utilization/Assimilation Hormones Degradation Melatonin Degradation

Some taxa known to possess this pathway include ? : Anolis carolinensis , Carassius auratus , Gallus gallus , Homo sapiens , Mesocricetus auratus , Mus musculus , Oncorhynchus mykiss , Oryctolagus cuniculus , Rattus norvegicus , Sceloporus jarrovii , Xenopus laevis

Expected Taxonomic Range: Vertebrata

Summary:
General Background

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 demonstrated in the non-mammalian vertebrate eye, pineal gland, brain and skin [Grace94, Grace91, Cahill89, Yanez96]. It has also been shown in mammalian skin [Slominski05a, Slominski05]. 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]).

Superpathways: superpathway of melatonin degradation

Variants: melatonin degradation I , melatonin degradation III

Credits:
Created 07-Dec-2009 by Fulcher CA , SRI International


References

Cahill89: Cahill GM, Besharse JC (1989). "Retinal melatonin is metabolized within the eye of xenopus laevis." Proc Natl Acad Sci U S A 86(3);1098-102. PMID: 2492661

Fischer06: Fischer TW, Sweatman TW, Semak I, Sayre RM, Wortsman J, Slominski A (2006). "Constitutive and UV-induced metabolism of melatonin in keratinocytes and cell-free systems." FASEB J 20(9);1564-6. PMID: 16793870

Grace91: Grace MS, Cahill GM, Besharse JC (1991). "Melatonin deacetylation: retinal vertebrate class distribution and Xenopus laevis tissue distribution." Brain Res 559(1);56-63. PMID: 1782560

Grace93: Grace MS, Besharse JC (1993). "Solubilization and biochemical characterization of the melatonin deacetylase from Xenopus laevis retina." J Neurochem 60(3);990-9. PMID: 8436983

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

Hardeland03: Hardeland R, Poeggeler B (2003). "Non-vertebrate melatonin." J Pineal Res 34(4);233-41. PMID: 12662344

Hardeland06: Hardeland R, Pandi-Perumal SR, Cardinali DP (2006). "Melatonin." Int J Biochem Cell Biol 38(3);313-6. PMID: 16219483

Hardeland08: Hardeland R (2008). "Melatonin, hormone of darkness and more: occurrence, control mechanisms, actions and bioactive metabolites." Cell Mol Life Sci 65(13);2001-18. PMID: 18344019

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

Semak05: Semak I, Naumova M, Korik E, Terekhovich V, Wortsman J, Slominski A (2005). "A novel metabolic pathway of melatonin: oxidation by cytochrome C." Biochemistry 44(26);9300-7. PMID: 15981996

Slominski05: Slominski A, Wortsman J, Tobin DJ (2005). "The cutaneous serotoninergic/melatoninergic system: securing a place under the sun." FASEB J 19(2);176-94. PMID: 15677341

Slominski05a: 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

Slominski08: Slominski A, Tobin DJ, Zmijewski MA, Wortsman J, Paus R (2008). "Melatonin in the skin: synthesis, metabolism and functions." Trends Endocrinol Metab 19(1);17-24. PMID: 18155917

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

Van01a: Van Tassel DL, Roberts N, Lewy A, O'Neill SD (2001). "Melatonin in plant organs." J Pineal Res 31(1);8-15. PMID: 11485009

Yanez96: Yanez J, Meissl H (1996). "Secretion of the methoxyindoles melatonin, 5-methoxytryptophol, 5-methoxyindoleacetic acid, and 5-methoxytryptamine from trout pineal organs in superfusion culture: effects of light intensity." Gen Comp Endocrinol 101(2);165-72. PMID: 8812361

Other References Related to Enzymes, Genes, Subpathways, and Substrates of this Pathway

Houslay74: Houslay MD, Tipton KF (1974). "A kinetic evaluation of monoamine oxidase activity in rat liver mitochondrial outer membranes." Biochem J 139(3);645-52. PMID: 4850215

Latendresse13: Latendresse M. (2013). "Computing Gibbs Free Energy of Compounds and Reactions in MetaCyc."

Raynaud91: Raynaud F, Pevet P (1991). "5-Methoxytryptamine is metabolized by monoamine oxidase A in the pineal gland and plasma of golden hamsters." Neurosci Lett 123(2);172-4. PMID: 2027530


Report Errors or Provide Feedback
Please cite the following article in publications resulting from the use of MetaCyc: Caspi et al, Nucleic Acids Research 42:D459-D471 2014
Page generated by SRI International Pathway Tools version 18.5 on Sun Nov 23, 2014, BIOCYC14B.