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Pathway Description
Eumelanin Biosynthesis
Homo sapiens
Metabolic Pathway
Created: 2019-03-22
Last Updated: 2019-09-13
Melanin is the term used for multiple pigments found in many organisms, and specifically our skin, hair and iris tissues. There are three types of melanin, eumelanin, pheomelanin and neuromelanin. Eumelanin is the most common, and can be brown or black. Melanin is produced by melanocytes, and is a polymer made of smaller components, so there are many types with different polymerization patterns and proportions of components.
To begin, this pathway takes L-dopachrome from the L-dopa and L-dopachrome biosynthesis pathways and, in the melanosome, it can either spontaneously form 5,6-dihydroxyindole, or can form 5,6-dihydroxyindole-2-carboxylic acid using L-dopachrome tautomerase as the catalyst. Both 5,6-dihydroxyindole and 5,6-dihydroxyindole-2-carboxylic acid use tyrosinase as a catalyst to form indole-5,6-quinone and indole-5,6-quinone-2-carboxylate respectively. Finally, some combination of 5,6-hydroxyindole, indole-5,6-quinone, 5,6-dihydroxyindole-2-carboxylic acid and indole-5,6-quinone-2-carboxylate combine to form melanochrome, an intermediate in the formation of eumelanin, and finally forms eumelanin, the final product of this pathway.
References
Eumelanin Biosynthesis References
Boissy RE, Sakai C, Zhao H, Kobayashi T, Hearing VJ: Human tyrosinase related protein-1 (TRP-1) does not function as a DHICA oxidase activity in contrast to murine TRP-1. Exp Dermatol. 1998 Aug;7(4):198-204.
Pubmed: 9758418
Jimenez-Cervantes C, Solano F, Kobayashi T, Urabe K, Hearing VJ, Lozano JA, Garcia-Borron JC: A new enzymatic function in the melanogenic pathway. The 5,6-dihydroxyindole-2-carboxylic acid oxidase activity of tyrosinase-related protein-1 (TRP1). J Biol Chem. 1994 Jul 8;269(27):17993-8000.
Pubmed: 8027058
Kobayashi T, Hearing VJ: Direct interaction of tyrosinase with Tyrp1 to form heterodimeric complexes in vivo. J Cell Sci. 2007 Dec 15;120(Pt 24):4261-8. doi: 10.1242/jcs.017913. Epub 2007 Nov 27.
Pubmed: 18042623
Kobayashi T, Urabe K, Winder A, Jimenez-Cervantes C, Imokawa G, Brewington T, Solano F, Garcia-Borron JC, Hearing VJ: Tyrosinase related protein 1 (TRP1) functions as a DHICA oxidase in melanin biosynthesis. EMBO J. 1994 Dec 15;13(24):5818-25.
Pubmed: 7813420
Kobayashi T, Urabe K, Winder A, Tsukamoto K, Brewington T, Imokawa G, Potterf B, Hearing VJ: DHICA oxidase activity of TRP1 and interactions with other melanogenic enzymes. Pigment Cell Res. 1994 Aug;7(4):227-34.
Pubmed: 7855068
Kobayashi T, Imokawa G, Bennett DC, Hearing VJ: Tyrosinase stabilization by Tyrp1 (the brown locus protein). J Biol Chem. 1998 Nov 27;273(48):31801-5. doi: 10.1074/jbc.273.48.31801.
Pubmed: 9822646
Korner AM, Gettins P: Synthesis in vitro of 5,6-dihydroxyindole-2-carboxylic acid by dopachrome conversion factor from Cloudman S91 melanoma cells. J Invest Dermatol. 1985 Sep;85(3):229-31. doi: 10.1111/1523-1747.ep12276688.
Pubmed: 4031539
Munoz-Munoz JL, Garcia-Molina F, Varon R, Tudela J, Garcia-Canovas F, Rodriguez-Lopez JN: Generation of hydrogen peroxide in the melanin biosynthesis pathway. Biochim Biophys Acta. 2009 Jul;1794(7):1017-29. doi: 10.1016/j.bbapap.2009.04.002. Epub 2009 Apr 15.
Pubmed: 19374959
Olivares C, Jimenez-Cervantes C, Lozano JA, Solano F, Garcia-Borron JC: The 5,6-dihydroxyindole-2-carboxylic acid (DHICA) oxidase activity of human tyrosinase. Biochem J. 2001 Feb 15;354(Pt 1):131-9. doi: 10.1042/0264-6021:3540131.
Pubmed: 11171088
Sarangarajan R, Boissy RE: Tyrp1 and oculocutaneous albinism type 3. Pigment Cell Res. 2001 Dec;14(6):437-44.
Pubmed: 11775055
Winder A, Kobayashi T, Tsukamoto K, Urabe K, Aroca P, Kameyama K, Hearing VJ: The tyrosinase gene family--interactions of melanogenic proteins to regulate melanogenesis. Cell Mol Biol Res. 1994;40(7-8):613-26.
Pubmed: 7787879
Yokoyama K, Suzuki H, Yasumoto K, Tomita Y, Shibahara S: Molecular cloning and functional analysis of a cDNA coding for human DOPAchrome tautomerase/tyrosinase-related protein-2. Biochim Biophys Acta. 1994 Apr 6;1217(3):317-21. doi: 10.1016/0167-4781(94)90292-5.
Pubmed: 8148378
Cassady JL, Sturm RA: Sequence of the human dopachrome tautomerase-encoding TRP-2 cDNA. Gene. 1994 Jun 10;143(2):295-8. doi: 10.1016/0378-1119(94)90114-7.
Pubmed: 8206391
Bouchard B, Del Marmol V, Jackson IJ, Cherif D, Dubertret L: Molecular characterization of a human tyrosinase-related-protein-2 cDNA. Patterns of expression in melanocytic cells. Eur J Biochem. 1994 Jan 15;219(1-2):127-34. doi: 10.1111/j.1432-1033.1994.tb19922.x.
Pubmed: 8306979
Tripathi RK, Strunk KM, Giebel LB, Weleber RG, Spritz RA: Tyrosinase gene mutations in type I (tyrosinase-deficient) oculocutaneous albinism define two clusters of missense substitutions. Am J Med Genet. 1992 Jul 15;43(5):865-71. doi: 10.1002/ajmg.1320430523.
Pubmed: 1642278
Giebel LB, Strunk KM, Spritz RA: Organization and nucleotide sequences of the human tyrosinase gene and a truncated tyrosinase-related segment. Genomics. 1991 Mar;9(3):435-45.
Pubmed: 1903356
Kwon BS, Haq AK, Pomerantz SH, Halaban R: Isolation and sequence of a cDNA clone for human tyrosinase that maps at the mouse c-albino locus. Proc Natl Acad Sci U S A. 1987 Nov;84(21):7473-7. doi: 10.1073/pnas.84.21.7473.
Pubmed: 2823263
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