What is melanogenesis?Melanogenesis is the biochemical process of melanin production. Melanogenesis pathway is catalyzed by the tyrosinase enzyme.
- Web definition of melanogenesis
- merriam-webster.com defines as: "the formation of melanin."
- Drugs.com defines as: "formation of melanin."
- Collinsdictionary.com defines as: "the production of melanin."
Mechanisms regulating melanogenesis and its pathwaysMelanin production takes place in the melanosomes, which are membrane-bound organelles located inside the melanocytes. Melanosomes are synthesized in the melanocytes. They are sites of synthesis, storage and transport of melanin.
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A base level melanogenesis is carried on continuously in the melanosomes to keep up with the genetically determined level of melanin. Exposure to UV radiation enhances the melanin production by activating tyrosinase enzyme for melanogenesis.
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Tyrosinase regulation of melanogenesisTyrosinase, a glycoprotein, is the principal enzyme involved in the melanin production. The tyrosinase is a single membrane-spanning transmembrane protein, spanning the entirety of the melanosomal membrane. It span from one side of the melanosomal membrane through to the other side of the membrane and is permanently attached. Most of the tyrosinase protein is present inside the melanosomal vesicle, which is the catalytic region of melanogenesis pathway. Only a small part of tyrosinase traverses the melanosomal membrane and projects into cytoplasm. The histidine residues present in the catalytic region bind to copper ions for tyrosinase activation.
Melanogenesis pathwayL-tyrosine is a non-essential amino acid as it can be synthesized by the body. Being a proteinogenic amino acid, it is the building block as well as the pathway in the synthesis of many cellular proteins, enzymes and catalysts. L-tyrosine [L-2-Amino-3-(4-hydroxyphenyl)propanoic acid] is the precursor to the melanin.
L-phenylalanine to l-tyrosine pathway
L-tyrosine has to reach the melanosomes only by the process of spontaneous passive transport which leads its insufficiency in the melanogenesis pathway.
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L-phenylalanine ››› intracellular phenylalanine hydroxylase (PAH) enzyme ››› L-tyrosineL-dopaquinone synthesis pathway
In the melanogenesis pathway, tyrosinase enzyme catalyses the hydroxylation of l-tyrosine to l-dihydroxyphenylalanine (L-DOPA) and the subsequent oxidation of L-DOPA to l-dopaquinone. With the formation of dopaquinone, the melanogenesis pathway is bifurcated into synthesis of the eumelanin and pheomelanin.
L-tyrosine ››› tyrosinase catalyst ››› L-dihydroxyphenylalanine (L-DOPA) ››› tyrosinase catalyst ››› L-dopaquinoneEumelanogenesis pathway
In this intermediate melanogenesis pathway, l-dopaquinone reacts with cysteine (which is actively transported across melanosomal membrane) to form either 5-S-cysteinyl-dopa or 2-S-cysteinyl-dopa. Both these cysteinyl-dopa intermediates, convert to benzothiazine intermediate and then polymerize to pheomelanin at the end of the melanogenesis pathway.
Dopaquinone + cysteine ››› 5-S-cysteinyldopa ››› benzothiazine intermediate ››› polymerization ››› pheomelanin
Dopaquinone + cysteine ››› 2-S-cysteinyldopa ››› benzothiazine intermediate ››› polymerization ››› pheomelaninPheomelanogenesis pathway
In this intermediate melanogenesis pathway, l-dopaquinone is converted spontaneously into from leucodopachrome and then dopachrome. Dopachrome is either converted spontaneously into 5,6-dihydroxyindole (indole) or convert to 5,6-dihydroxyindole-2-carboxylic acid by the enzymatic action of dopachrome tautomerase (DCT). Both these intermediates convert to quinone and then polymerize to eumelanin.
Dopaquinone ››› spontaneous conversion ››› leucodopachrome ››› spontaneous conversion ››› dopachrome ››› dopachrome tautomerase (DCT) catalyst ››› 5,6-dihydroxyindole-2-carboxylic acid ››› quinone ››› polymerization ››› eumelanin
Dopaquinone ››› spontaneous conversion ››› leucodopachrome ››› spontaneous conversion ››› dopachrome ››› spontaneous conversion ››› 5,6-dihydroxyindole ››› quinone ››› polymerization ››› eumelanin
1.Inês Ferreira dos Santos Videira, Daniel Filipe Lima Moura, Sofia Magina. Mechanisms regulating melanogenesis. An Bras Dermatol. 2013 Jan-Feb; 88(1): 76–83.
2.Park HY, Kosmadaki M, Yaar M, Gilchrest BA. Cellular mechanisms regulating human melanogenesis. Cell Mol Life Sci. 2009 May;66(9):1493-506.
3.Gillbro, J. M. Olsson, M. J. The melanogenesis and mechanisms of skin-lightening agents – existing and new approaches. International Journal of Cosmetic Science, 33: 210–221.
4.Agar N, Young AR. Melanogenesis: a photoprotective response to DNA damage? Mutat Res. 2005 Apr 1;571(1-2):121-32. Epub 2005 Jan 23.
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