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How Melanin is Produced

Written by: Jake Khalde


Imagine yourself spending a day at the beach on a hot summer day. After a day filled with sun and fun, you go home, ready to take that satisfying post-beach shower. You look in the mirror and notice that your cheeks are sun-kissed. You get excited because who doesn’t love a good tan? (Hint: your skin cells.) But you start to wonder, “How does this happen?”

Skin melanization happens because of melanogenesis, a process of the production and distribution of melanin. Melanin is what colors your skin, hair, and eye. It is what your skin makes when it undergoes damage by the sun as a form of self-protection, but melanin has a smaller SPF factor to it - a rating of about SPF 1-4, so sunscreen is still the way to go! There are three types of melanin: eumelanin, pheomelanin, and neuromelanin. Eumelanin make black/brown pigments, and pheomelanin make red/yellow pigments. Unlike the other types of melanin, neuromelanin functions as an antioxidant that inhibits toxic compounds and metals, thus protecting neurons.

It is necessary to establish that melanocytes are the cells that produce melanin through melanosomes. Melanocytes start from migratory embryonic cells, called neural crest melanoblast cells (melanoblasts are the precursors to melanocytes). These neural crest melanoblasts cells move to the epidermis, among other places. Melanosomes form and mature in the melanocytes in four stages, and each produces a different type of melanin - yup, that’s right: there is more than one type of melanin! The first two stages are “early” melanosomes, and the last two stages are “late” melanosomes. It isn’t fully understood how early melanosomes in stage one form in the first place, but the melanosomes in stage one have some of the same proteins as in other locations: the endoplasmic reticulum, endosomes, lysosomes, and coated vesicles.

In the first stage of melanosome formation and maturation, a vesicle (sac) forms. In the second stage, the melanosome elongates and receives the enzymes needed for melanogenesis: tyrosinase, tyrosinase-related protein one, and tyrosine-related protein two. Tyrosinase is the only enzyme critical for melanogenesis, though. Stage three of melanosome formation and maturation is where the real action starts: the melanosome starts producing the melanin polymers (more than one melanin that forms a group, or a polymer, of the single compound melanin, the monomer), which then lay on the fibrils, small fibers, of the melanosome! In the last stage, stage four, the melanin finally has made the melanin type it is supposed to make.

Melanogenesis is a complex process of many stages. It starts with the hydroxylation of the protein tyrosine to L-3,4-dihydroxyphenylalanine (DOPA). The brown and black pigment-producing melanin, eumelanin, is made when the amino acid cysteine or antioxidant glutathione is absent. The yellow and orange pigment-producing melanin, pheomelanin, is created when there are a lot of cysteines in the DOPAquinone, a converted form of DOPA, with the help of the tyrosine catalyst again. Unlike eumelanin and pheomelanin, neuromelanin is produced when free dopamine in the cytoplasm oxidizes to unstable ortho-quinones (dopamine-o-quinone, aminochrome, and indole-5,6-quinone). Then, the ortho-quinones polymerize to make a structure of indole-5,6-quinone. Different than pheomelanin and eumelanin, neuromelanin synthesis does not involve tyrosine.

The skin produces melanin after sun damage as a form of self-protection. You may have heard that a base tan is healthy and protective, but it is not: any tan is a sign of sun damage. Even if there is no period of burning or blistering, a tan is a sign of sun damage already done. Dermatologist Ranella Hirsch says that “a tan means that you’ve already responded to UV injury” on her Instagram page. Even with melanin’s protective nature, it does not have enough SPF for anyone - not even those with heavily melanated skin (again, an SPF range estimated to be 1-4) have enough sun protection from melanin.

Melanin production in the skin is not identical to melanin produced in neurons, but both have complex biological and chemical processes. Behind every beach trip tan is a complex biological process.


Sources:


Brenner, Michaela, and Vincent J. Hearing. “The Protective Role of Melanin Against UV Damage in Human Skin.” NCBI, 2009, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2671032/. Accessed 10 June 2022.


Chang, Te. “Natural Melanogenesis Inhibitors Acting Through the Down-Regulation of Tyrosinase Activity.” NCBI, 2012, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5449013/. Accessed 10 June 2022.


Cichorek, Miroslawa, et al. “Heterogeneity of neural crest-derived melanocytes.” Research Gate, Research Gate, April 2013, https://www.researchgate.net/publication/236622051_Heterogeneity_of_neural_crest-derived_melanocytes. Accessed 9 June 2022.


Dermatol, An Bras. “Mechanisms regulating melanogenesis - PMC.” NCBI, 2013, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3699939/. Accessed 10 June 2022.


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