Biochemistry, Melanin (2024)

Introduction

Melanin is a term used to describe a large group of related molecules responsible for many biological functions, including pigmentation of skin and hair and photoprotection of skin and eye.[1][2][3]

Fundamentals

In humans, melanin exists as three forms: eumelanin (which is subdividedfurtherinto black and brown forms), pheomelanin, and neuromelanin.

Cellular Level

Eumelanin and pheomelanin are produced in various amounts in the basal layer of the epidermis within cells called melanocytes. Melanocytes are the mature forms of melanoblasts, which migrate from the neural crest following neural tube closure. As melanin is produced within melanocytes, it is packaged in small, round membrane-bound organelles called melanosomes. Melanosomes are transported from melanocytes to neighboring keratinocytes via tentacle-like dendritic processes. Melanosomes arriving in keratinocytes are positioned superficially to cell nuclei, which serves to protect from incoming ultraviolet (UV) radiation.[4]

Molecular Level

The first step of biosynthesis of both eumelanin and pheomelanin begins the same way. Tyrosine is converted into dihydroxyphenylalanine (DOPA), which requires tyrosine hydroxylase and tetrahydrobiopterin as a cofactor. The enzyme tyrosinase then convertsdihydroxyphenylalanineinto dopaquinone, which can follow a variety of pathways to form the eumelanin or pheomelanin.

The primary stimulus for melanogenesis and subsequent melanosome production is UV radiation, which upregulates melanocyte production of pro-opiomelanocortin (POMC) and its downstream products, alpha-melanocyte-stimulating hormone (alpha-MSH) and adrenocorticotropic hormone (ACTH). The overall effect is to increase eumelanin production. (Interestingly, people withpro-opiomelanocortinmutations have red hair and Fitzpatrick skin type 1 due to the relative increase in pheomelanin to eumelanin expression).

Neuromelanin is a dark pigment produced by dopaminergic and noradrenergic cells of the substantia nigra and locus coeruleus as a breakdown product of dopamine.[5]

Function

In its various forms, melanin fulfills a variety of biological functions, including skin and hair pigmentation and photoprotection of the skin and eye.

Pigmentation of the skin results from the accumulation of melanin-containing melanosomes in the basal layer of the epidermis. Differences in skin pigmentation result both from the relative ratio of eumelanin (brown–black) to pheomelanin (yellow–red), as well as the number of melanosomes within melanocytes. Pheomelanin accounts for the pinkish skin constituting the lips, nipples, vagin*, and glans of the penis. In general, lightly pigmented skin tends to contain melanocytes with clusters of two to three melanosomes, whereas darkly pigmented skin tends to contain individual melanosomes which can melanize neighboring keratinocytes more readily. The overall melanin density correlates with the darkness of skin as well as Fitzpatrick skin type.

The interplay between melanin and UV radiation is complex. Researcherswidely believe that melanin production in melanocytes increased as an evolutionary adaptation to the widespread loss of human body hair more than a million years ago. Populations living closer to the equator tended to develop a greater proportion of eumelanin, which is a UV–absorbent, antioxidant, and free radical scavenger. Conversely, populations living further from the equator are relatively richer in pheomelanin, which produces free radicals in response to UV radiation, accelerating carcinogenesis. As the main stimulus for cutaneous vitamin D production is UV light exposure, it follows that dark-skinned individuals also tend to have lower levels of vitamin D and should be screened accordingly.

Less clear is the link between melanin, the sun, and cutaneous immunology. Both acute and chronic UV light exposure induces immunosuppression; UVA light is used therapeutically for a large number of skin conditions, including psoriasis. Intriguingly, melanin is believed to have immunomodulatory and even anti-bacterial properties, although the underlying mechanisms have not yet been fully elucidated. Malignant melanocytes rich in melanin are less sensitive to chemo-, radio-, or photodynamic therapy, and amelanotic melanomas have longer disease-free and overall survival than melanotic ones. Therefore, some have suggested inhibition of melanogenesis as a therapy for malignant melanoma.

Just as melanin protects the skin from photodamage, it also protects the eye. Melanin is concentrated in the iris and choroid, and those with grey, blue, and green eye colors, as well as albinos, have more sun-related ocular issues.

Hair color is determined by the relative proportion of various forms of melanin:

  • Black and brown hair results from varying degrees of black and brown eumelanin

  • Blonde hair results from a small amount of brown eumelanin in the absence of black eumelanin

  • Red hair results from roughly equal amounts of pheomelanin as eumelanin. Strawberry blonde hair results from brown eumelanin in the presence of pheomelanin.

Clinical Significance

Each step in the formation and transport of melanin may be impaired, resulting in a diverse group of diseases:[6][7][8]

  • Melanoblast:Waardenburg syndrome, a group of autosomal recessive (AR) and dominant (AD) diseases characterized by a white forelock, skin hypopigmentation, and premature graying of the hair, results from impaired melanoblast migration to their destination tissue (i.e., iris, hair). Various forms also include congenital deafness, heterochromia iridis, synophrys, and dystopia canthorum.

  • Melanocyte:Vitiligo, a disease characterized by photosensitive and depigmented white patches surrounded by normally pigmented skin and ophthalmologic issues, results from auto-immune destruction of melanocytes.

  • Melanosome:Chédiak-Higashi syndrome, an autosomal recessive disease characterized by partial oculocutaneous albinism, platelet dysfunction, hemophagocytic lymphohistiocytosis (HLH), and immunodeficiency, results from mutations in genes which likely regulate lysosomal trafficking.Griscelli syndrome, anautosomal recessivegroup of diseases, characterized by hair and skin hypopigmentation, results from mutations in the protein complex responsible for the transfer of mature melanosomes to keratinocytes. Various forms also include neurologic impairment, immunodeficiency, and HLH.

  • Tyrosinase:Phenylketonuria, anautosomal recessivedisease characterized by intellectual disability, epilepsy, fair, blonde hair and blue eyes, and other skin changes, results from a deficiency of the phenylalanine hydroxylase enzyme. The pigmentary changes are due to competitive inhibition of tyrosinase by phenylalanine buildup.Oculocutaneous albinism, a group ofautosomal recessivediseases characterized by hypopigmentation and ocular problems, results from mutations of the tyrosinase (TYR) gene.Vogt-Koyanagi-Harada syndrome, a disease characterized by progression through phases of meningoencephalitis, uveitis, alopecia with vitiligo-like depigmentation, and recurrent uveitis, results from autoimmune destruction of melanosome-bound antigens, possibly including the tyrosinase enzyme itself.

  • Dopaminergic neurons:Parkinson disease, a neurodegenerative condition characterized by progressive postural and gait difficulties, results from drop-out of neuromelanin-producing dopaminergic neurons in the brain. Depigmentation of the substantia nigra pars compacta is a pathologic hallmark of the condition.

References

1.

Maranduca MA, Branisteanu D, Serban DN, Branisteanu DC, Stoleriu G, Manolache N, Serban IL. Synthesis and physiological implications of melanic pigments. Oncol Lett. 2019 May;17(5):4183-4187. [PMC free article: PMC6444329] [PubMed: 30944614]

2.

Fernandez-Flores A, Saeb-Lima M, Cassarino DS. Histopathology of aging of the hair follicle. J Cutan Pathol. 2019 Jul;46(7):508-519. [PubMed: 30932205]

3.

Starace M, Alessandrini A, Brandi N, Piraccini BM. Use of Nail Dermoscopy in the Management of Melanonychia: Review. Dermatol Pract Concept. 2019 Jan;9(1):38-43. [PMC free article: PMC6368078] [PubMed: 30775147]

4.

D'Alba L, Shawkey MD. Melanosomes: Biogenesis, Properties, and Evolution of an Ancient Organelle. Physiol Rev. 2019 Jan 01;99(1):1-19. [PubMed: 30255724]

5.

Del Bino S, Duval C, Bernerd F. Clinical and Biological Characterization of Skin Pigmentation Diversity and Its Consequences on UV Impact. Int J Mol Sci. 2018 Sep 08;19(9) [PMC free article: PMC6163216] [PubMed: 30205563]

6.

Juhasz MLW, Levin MK. The role of systemic treatments for skin lightening. J Cosmet Dermatol. 2018 Dec;17(6):1144-1157. [PubMed: 30133125]

7.

Saleem MD. Biology of human melanocyte development, Piebaldism, and Waardenburg syndrome. Pediatr Dermatol. 2019 Jan;36(1):72-84. [PubMed: 30561083]

8.

Carballo-Carbajal I, Laguna A, Romero-Giménez J, Cuadros T, Bové J, Martinez-Vicente M, Parent A, Gonzalez-Sepulveda M, Peñuelas N, Torra A, Rodríguez-Galván B, Ballabio A, Hasegawa T, Bortolozzi A, Gelpi E, Vila M. Brain tyrosinase overexpression implicates age-dependent neuromelanin production in Parkinson's disease pathogenesis. Nat Commun. 2019 Mar 07;10(1):973. [PMC free article: PMC6405777] [PubMed: 30846695]

Biochemistry, Melanin (2024)

FAQs

Biochemistry, Melanin? ›

Melanin pigments are large polymers synthesized from amino acids that have strong light-absorbing capabilities across the ultraviolet–visible spectrum (Prota 1992). They occur in two main forms: (1) eumelanin

eumelanin
Eumelanin is a black-brown pigment that is a chemically diverse biomacromolecule with functional properties relevant to technology, such as photoprotection, metal ion chelation, and redox activity.
https://www.sciencedirect.com › topics › chemistry › eumelanin
, which confers black and grey colours, and (2) phaeomelanin
phaeomelanin
Pheomelanin is the pigment responsible for producing red hair color and is produced through a polymorphic melanocortin-1 receptor gene (MC1R). From: Best Practice & Research Clinical Anaesthesiology, 2018.
https://www.sciencedirect.com › topics › pheomelanin
, which bestows chestnut and buff colours.

What 3 components make up melanin? ›

Melanin's molecular composition includes a mix of carbon (pink), hydrogen (white), oxygen (blue), and nitrogen (green). The chemical formula of melanin is C18H10N2O4. It has a molar mass of 318 g/mole (for every 318 g of melanin, there are 6.02 x 10^23 molecules of melanin).

What is the chemical function of melanin? ›

Melanin is a substance in your body that produces hair, eye and skin pigmentation. The more melanin you produce, the darker your eyes, hair and skin will be. The amount of melanin in your body depends on a few different factors, including genetics and how much sun exposure your ancestral population had.

What triggers melanin production? ›

A major extrinsic regulator of melanogenesis is ultraviolet radiation (UVR), including UVA and UVB light. This is the main stimulus for melanin production, leading to induced pigmentation of the skin, or 'tanning'.

What is the enzyme that produces melanin? ›

The TYRP1 gene provides instructions for making an enzyme called tyrosinase-related protein 1. This enzyme is located in melanocytes, which are specialized cells that produce a pigment called melanin. Melanin is the substance that gives skin, hair, and eyes their color.

What organ produces melanin? ›

Eumelanin and pheomelanin are in the epidermis, which is one of the layers of the skin. By contrast, neuromelanin is present in the brain. Melanocytes are the cells that produce eumelanin and pheomelanin. Cells known as keratinocytes then carry melanin to the skin surface.

Can you increase your melanin? ›

Can you increase melanin? People of any skin type can try increasing melanin to reduce skin cancer risk. Studies suggest that upping your intake of certain nutrients could increase melanin levels. It might even increase the amount of melanin in people with fair skin types.

Is melanin a protein or hormone? ›

Melanin (/ˈmɛlənɪn/; from Ancient Greek μέλας (mélas) 'black, dark') is a family of biomolecules organized as oligomers or polymers, which among other functions provide the pigments of many organisms. Melanin pigments are produced in a specialized group of cells known as melanocytes.

What is melanin stimulated by? ›

Acting through melanocortin 1 receptor, α-MSH stimulates the production and release of melanin (a process referred to as melanogenesis) by melanocytes in skin and hair. Acting in the hypothalamus, α-MSH suppresses appetite.

Is melanin acidic or alkaline? ›

The process of melanin formation takes place in specialized acidic organelles (melanosomes) in melanocytes. The process of melanin polymerization requires an alkaline pH in vitro, and therefore, the purpose of an acidic environment in vivo remains a mystery. It is known that melanin is always bound to protein in vivo.

What depletes melanin? ›

Skin lightening treatments can temporarily reduce your skin's melanin production. Most of them work by suppressing the enzyme that's needed to form melanin. However, aside from wearing sunscreen and limiting sun exposure, you cannot lower your body's overall melanin production.

What can I eat to increase melanin? ›

Foods that may increase melanin in hair include antioxidant-rich foods like berries, nuts, beans, citrus fruits, and leafy greens. Eating foods high in copper, such as crab meat, almonds, lentils, peanuts, and beef liver, may also support melanin production in hair.

Which amino acid creates melanin? ›

The melanic pigments, eumelanin and pheomelanin, are the final product of complex biochemical reactions starting from the amino acid L-tyrosine. Melanin has a major role in skin homeostasis through the photoprotection it offers from the harmful effect of ultraviolet radiation.

What causes deficiency of melanin? ›

Melanin deficiency has previously been associated with various genetic abnormalities and congenital defects. Some of the diseases associated with melanin include: Albinism - There are almost ten different types of oculocutaneous albinism, conditions that are inherited in an autosomal recessive manner.

What regulates melanin? ›

The pigment melanin is produced in melanosomes by melanocytes in a complex process called melanogenesis. The melanocyte interacts with endocrine, immune, inflammatory and central nervous systems, and its activity is also regulated by extrinsic factors such as ultraviolet radiation and drugs.

What gene controls melanin? ›

The MC1R gene provides instructions for making a protein called the melanocortin 1 receptor. This receptor plays an important role in normal pigmentation. The receptor is primarily located on the surface of melanocytes, which are specialized cells that produce a pigment called melanin.

What are the three main types of melanin? ›

In humans, melanin exists as three forms: eumelanin (which is subdivided further into black and brown forms), pheomelanin, and neuromelanin.

What are the three shades of melanin? ›

Types of Melanin
  • Eumelanin makes mostly dark colors in hair, eyes, and skin, and includes two types: brown and black. ...
  • Pheomelanin colors the pinkish parts of your body, such as your lips and nipples. ...
  • Neuromelanin controls the colors of neurons, which are nerve cells that send messages throughout your body.
Oct 10, 2023

What are the 3 pigments that contribute to skin color? ›

The color of skin is influenced by a number of pigments, including melanin, carotene, and hemoglobin. Recall that melanin is produced by cells called melanocytes, which are found scattered throughout the stratum basale of the epidermis.

What is the ingredient melanin? ›

Melanin is a natural product found in Streptomyces nodosus, Streptomyces avermitilis, and other organisms with data available. Insoluble polymers of TYROSINE derivatives found in and causing darkness in skin (SKIN PIGMENTATION), hair, and feathers providing protection against SUNBURN induced by SUNLIGHT.

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