Melanin

Source: Wikipedia, the free encyclopedia.
(Redirected from
Eumelanin
)
Not to be confused with Melamine or Melatonin.

Melanin
One possible structure of Eumelanin
One possible structure of Eumelanin
Material typeHeterogeneous Biopolymer
Micrograph of Melanin pigment (light refracting granular material—center of image) in a pigmented melanoma.
Micrograph of the epidermis, with melanin labeled at left.

Melanin (

melanocytes. They have been described as "among the last remaining biological frontiers with the unknown".[1]

There are five basic types of melanin:

Parkinson's.[3]
Allomelanin and pyomelanin are two types of nitrogen-free melanin.

In the human skin, melanogenesis is initiated by exposure to

skin tone.[5]

Melanin types

Eumelanin

Part of the structural formula of eumelanin. "(COOH)" can be COOH or H, or (more rarely) other substituents. The arrow denotes where the polymer continues.

Eumelanin has two forms linked to

5,6-dihydroxyindole (DHI) and 5,6-dihydroxyindole-2-carboxylic acid (DHICA). DHI-derived eumelanin is dark brown or black and insoluble, and DHICA -derived eumelanin which is lighter and soluble in alkali. Both eumelanins arise from the oxidation of tyrosine in specialized organelles called melanosomes. This reaction is catalyzed by the enzyme tyrosinase. The initial product, dopaquinone can transform into either 5,6-dihydroxyindole (DHI) or 5,6-dihydroxyindole-2-carboxylic acid (DHICA). DHI and DHICA are oxidized and then polymerize to form the two eumelanins.[6]

In natural conditions, DHI and DHICA often co-polymerize, resulting in a range of eumelanin polymers. These polymers contribute to the variety of melanin components in human skin and hair, ranging from light yellow/red pheomelanin to light brown DHICA-enriched eumelanin and dark brown or black DHI-enriched eumelanin. These final polymers differ in solubility and color.[6]

Analysis of highly pigmented (Fitzpatrick type V and VI) skin finds that DHI-eumelanin comprises the largest portion, approximately 60–70%, followed by DHICA-eumelanin at 25–35%, and pheomelanin only 2–8%. Notably, while an enrichment of DHI-eumelanin occurs in during sun tanning, it is accompanied by a decrease in DHICA-eumelanin and pheomelanin.[6] A small amount of black eumelanin in the absence of other pigments causes grey hair. A small amount of eumelanin in the absence of other pigments causes blond hair.[7] Eumelanin is present in the skin and hair, etc.

Pheomelanin

Part of the structural formula of pheomelanin. "(COOH)" can be COOH or H, or (more rarely) other substituents. The arrows denote where the polymer continues.

Pheomelanins (or phaeomelanins) impart a range of yellowish to reddish colors.[8] Pheomelanins are particularly concentrated in the lips, nipples, glans of the penis, and vagina.[9] When a small amount of eumelanin in hair (which would otherwise cause blond hair) is mixed with pheomelanin, the result is orange hair, which is typically called "red" or "ginger" hair. Pheomelanin is also present in the skin, and redheads consequently often have a more pinkish hue to their skin as well. Exposure of the skin to ultraviolet light increases pheomelanin content, as it does for eumelanin; but rather than absorbing light, pheomelanin within the hair and skin reflect yellow to red light, which may increase damage from UV radiation exposure.[10]

Pheomelanin production is highly dependent on

L-cysteine
is present.

Neuromelanin

Main article: Neuromelanin

Neuromelanin (NM) is an insoluble polymer pigment produced in specific populations of

transition metals such as iron, as well as other potentially toxic molecules. Therefore, it may play crucial roles in apoptosis and the related Parkinson's disease.[13]

Other forms of melanins

Up until the 1960s, melanin was classified into eumelanin and pheomelanin. However in 1955 a melanin associated with nerve cells was discovered, neuromelanin, in 1972 a water-soluble form, pyomelanin. In 1976, allomelanin, the fifth form of the melanins was found in nature.[2]

Selenomelanin

It is possible to enrich melanin with

sulphur. This selenium analogue of pheomelanin has been successfully synthesized through chemical and biosynthetic routes using selenocystine as a feedstock.[14] Due selenium's higher atomic number, the obtained selenomelanin can be expected to provide better protection against ionising radiation as compared to the other known forms of melanin. This protection has been demonstrated with radiation experiments on human cells and bacteria, opening up the possibility of applications in space travel.[15]

Trichochromes

Trichochromes (formerly called trichosiderins) are pigments produced from the same metabolic pathway as the eumelanins and pheomelanins, but unlike those molecules they have low molecular weight. They occur in some red human hair.[16]

Humans

Albinism occurs when melanocytes produce little melanin. This albino girl is from Papua New Guinea.

In humans, melanin is the primary determinant of skin color. It is also found in hair, the pigmented tissue underlying the iris of the eye, and the stria vascularis of the inner ear. In the brain, tissues with melanin include the medulla and pigment-bearing neurons within areas of the brainstem, such as the locus coeruleus. It also occurs in the zona reticularis of the adrenal gland.[17]

The melanin in the skin is produced by

epidermis. Although, in general, human beings possess a similar concentration of melanocytes in their skin, the melanocytes in some individuals and ethnic groups produce variable amounts of melanin. Some humans have very little or no melanin synthesis in their bodies, a condition known as albinism.[18]

Because melanin is an aggregate of smaller component molecules, there are many different types of melanin with different proportions and bonding patterns of these component molecules. Both pheomelanin and eumelanin are found in human skin and hair, but eumelanin is the most abundant melanin in humans, as well as the form most likely to be deficient in albinism.[19]

Other organisms

Melanins have very diverse roles and functions in various organisms. A form of melanin makes up the ink used by many

gamma rays[22] and harness this energy for growth.[23]

In

Cyprinus carpio use pheomelanin instead.[26][27]

The darker feathers of birds owe their color to melanin and are less readily degraded by bacteria than unpigmented ones or those containing carotenoid pigments.[28] Feathers that contain melanin are also 39% more resistant to abrasion than those that do not because melanin granules help fill the space between the keratin strands that form feathers.[29][30] Pheomelanin synthesis in birds implies the consumption of cysteine, a semi‐essential amino acid that is necessary for the synthesis of the antioxidant glutathione (GSH) but that may be toxic if in excess in the diet. Indeed, many carnivorous birds, which have a high protein content in their diet, exhibit pheomelanin‐based coloration.[31]

Melanin is also important in

agouti gene which regulates the distribution of melanin.[33][34] The mechanisms of the gene have been extensively studied in mice to provide an insight into the diversity of mammalian coat patterns.[35]

Melanin in

iridescent color.[36][37]

Arachnids are one of the few groups in which melanin has not been easily detected, though researchers found data suggesting spiders do in fact produce melanin.[38]

Some moth species, including the

wood tiger moth, convert resources to melanin to enhance their thermoregulation. As the wood tiger moth has populations over a large range of latitudes, it has been observed that more northern populations showed higher rates of melanization. In both yellow and white male phenotypes of the wood tiger moth, individuals with more melanin had a heightened ability to trap heat but an increased predation rate due to a weaker and less effective aposematic signal.[39]

Melanin protects

radiotrophic microbes in Chernobyl, and as of 2022 continues under the Belarusian Institute of Genetics and Cytology.[46] Her most significant contribution is Mosse et al., 2000 on mice[41][42][43][44][45][46][47]: 1151  but also includes Mosse et al., 1994,[45] Mosse et al., 1997,[45] Mosse et al., 1998,[44] Mosse et al., 2001,[45] Mosse et al., 2002,[44][45] Mosse et al., 2006,[44][45] Mosse et al., 2007[45] and Mosse et al., 2008.[45]

Plants

Chemical structure of indole-5,6-quinone

Melanin produced by plants are sometimes referred to as 'catechol melanins' as they can yield

catecholamines leading to the formation of catechol melanin. Despite this many plants contain compounds which inhibit the production of melanins.[49]

Interpretation as a single monomer

It is now understood that melanins do not have a single structure or stoichiometry. [citation needed] Nonetheless, chemical databases such as PubChem include structural and empirical formulae; typically 3,8-Dimethyl-2,7-dihydrobenzo[1,2,3-cd:4,5,6-c′d′]diindole-4,5,9,10-tetrone. This can be thought of as a single monomer that accounts for the measured elemental composition and some properties of melanin, but is unlikely to be found in nature.[50] Solano[50] claims that this misleading trend stems from a report of an empirical formula in 1948,[51] but provides no other historical detail.

3,8-Dimethyl-2,7-dihydrobenzo[1,2,3-cd:4,5,6-c′d′]diindole-4,5,9,10-tetrone
3,8-Dimethyl-2,7-dihydrobenzo[1,2,3-cd:4,5,6-c′d′]diindole-4,5,9,10-tetrone
3,8-Dimethyl-2,7-dihydrobenzo[1,2,3-cd:4,5,6-c′d′]diindole-4,5,9,10-tetrone ball and stick model
Names
Preferred IUPAC name
3,8-Dimethyl-2,7-dihydrobenzo[1,2,3-cd:4,5,6-c′d′]diindole-4,5,9,10-tetrone
Identifiers
ChemSpider
Properties
C18H10N2O4
Molar mass 318.288 g·mol−1
Density 1.6 to 1.8 g/cm3
Melting point < −20 °C (−4 °F; 253 K)
Boiling point 450 to 550 °C (842 to 1,022 °F; 723 to 823 K)
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).

Biosynthetic pathways

The first step of the biosynthetic pathway for both eumelanins and pheomelanins is catalysed by tyrosinase.[52]

dopaquinone

Dopaquinone can combine with cysteine by two pathways to benzothiazines and pheomelanins

Dopaquinone + cysteine → 5-S-cysteinyldopa → benzothiazine intermediate → pheomelanin
Dopaquinone + cysteine → 2-S-cysteinyldopa → benzothiazine intermediate → pheomelanin

Also, dopaquinone can be converted to leucodopachrome and follow two more pathways to the eumelanins

Dopaquinone → leucodopachrome → dopachrome → 5,6-dihydroxyindole-2-carboxylic acid → quinone → eumelanin
Dopaquinone → leucodopachrome → dopachrome → 5,6-dihydroxyindole → quinone → eumelanin

Detailed metabolic pathways can be found in the KEGG database (see External links).

  • L-tyrosine
    L-tyrosine
  • L-DOPA
    L-DOPA
  • L-dopaquinone
    L-dopaquinone
  • L-leucodopachrome
    L-leucodopachrome
  • L-dopachrome
    L-dopachrome

Microscopic appearance

Melanin is brown, non-refractile, and finely granular with individual granules having a diameter of less than 800 nanometers. This differentiates melanin from common blood breakdown pigments, which are larger, chunky, and refractile, and range in color from green to yellow or red-brown. In heavily pigmented lesions, dense aggregates of melanin can obscure histologic detail. A dilute solution of potassium permanganate is an effective melanin bleach.[53]

Genetic disorders and disease states

There are approximately nine types of

congenital reduction or absence of melanin pigment in the skin, hair, and eyes. The estimated frequency of OCA2 among African-Americans is 1 in 10,000, which contrasts with a frequency of 1 in 36,000 in white Americans.[54] In some African nations, the frequency of the disorder is even higher, ranging from 1 in 2,000 to 1 in 5,000.[55] Another form of Albinism, the "yellow oculocutaneous albinism", appears to be more prevalent among the Amish, who are of primarily Swiss and German ancestry. People with this IB variant of the disorder commonly have white hair and skin at birth, but rapidly develop normal skin pigmentation in infancy.[55]

Ocular albinism affects not only eye pigmentation but visual acuity, as well. People with albinism typically test poorly, within the 20/60 to 20/400 range. In addition, two forms of albinism, with approximately 1 in 2,700 most prevalent among people of Puerto Rican origin, are associated with mortality beyond melanoma-related deaths.

The connection between albinism and

melanocytes in the stria vascularis of the inner ear results in cochlear impairment,[59]
though why this is, is not fully understood.

In Parkinson's disease, a disorder that affects neuromotor functioning, there is decreased neuromelanin in the substantia nigra and locus coeruleus as a consequence of specific dropping out of dopaminergic and noradrenergic pigmented neurons. This results in diminished dopamine and norepinephrine synthesis. While no correlation between race and the level of neuromelanin in the substantia nigra has been reported, the significantly lower incidence of Parkinson's in blacks than in whites has "prompt[ed] some to suggest that cutaneous melanin might somehow serve to protect the neuromelanin in substantia nigra from external toxins."[60]

In addition to melanin deficiency, the molecular weight of the melanin polymer may be decreased by various factors such as oxidative stress, exposure to light, perturbation in its association with melanosomal

matrix proteins, changes in pH, or in local concentrations of metal ions. A decreased molecular weight or a decrease in the degree of polymerization of ocular melanin has been proposed to turn the normally anti-oxidant polymer into a pro-oxidant. In its pro-oxidant state, melanin has been suggested to be involved in the causation and progression of macular degeneration and melanoma.[61] Rasagiline, an important monotherapy drug in Parkinson's disease, has melanin binding properties, and melanoma tumor reducing properties.[62]

Higher eumelanin levels also can be a disadvantage, however, beyond a higher disposition toward vitamin D deficiency. Dark skin is a complicating factor in the laser removal of port-wine stains. Effective in treating white skin, in general, lasers are less successful in removing port-wine stains in people of Asian or African descent. Higher concentrations of melanin in darker-skinned individuals simply diffuse and absorb the laser radiation, inhibiting light absorption by the targeted tissue. In a similar manner, melanin can complicate laser treatment of other dermatological conditions in people with darker skin.

moles
are formed where there is a localized concentration of melanin in the skin. They are highly associated with pale skin.

Nicotine has an affinity for melanin-containing tissues because of its precursor function in melanin synthesis or its irreversible binding of melanin. This has been suggested to underlie the increased nicotine dependence and lower smoking cessation rates in darker pigmented individuals.[63]

Human adaptation

Physiology

Melanocytes insert granules of melanin into specialized cellular

epidermis. The melanosomes in each recipient cell accumulate atop the cell nucleus, where they protect the nuclear DNA from mutations caused by the ionizing radiation of the sun's ultraviolet rays. In general, people whose ancestors lived for long periods in the regions of the globe near the equator have larger quantities of eumelanin in their skins. This makes their skins brown or black and protects them against high levels of exposure to the sun, which more frequently result in melanomas in lighter-skinned people.[64]

Not all the effects of pigmentation are advantageous. Pigmentation increases the heat load in hot climates, and dark-skinned people absorb 30% more heat from sunlight than do very light-skinned people, although this factor may be offset by more profuse sweating. In cold climates dark skin entails more heat loss by radiation. Pigmentation also hinders synthesis of vitamin D. Since pigmentation appears to be not entirely advantageous to life in the tropics, other hypotheses about its biological significance have been advanced, for example a secondary phenomenon induced by adaptation to parasites and tropical diseases.[65]

Evolutionary origins

SLC24A5 has undergone positive selection.[70]

Effects

As with peoples having migrated northward, those with light skin migrating toward the equator acclimatize to the much stronger solar radiation. Nature selects for less melanin when ultraviolet radiation is weak. Most people's skin darkens when exposed to UV light, giving them more protection when it is needed. This is the physiological purpose of

solar radiation, including the photodegradation of certain vitamins such as riboflavins, carotenoids, tocopherol, and folate.[71]

Melanin in the eyes, in the

accommodation—the ability to change shape to focus from far to near—a detriment due probably to protein
crosslinking caused by UV exposure.

Recent research suggests that melanin may serve a protective role other than photoprotection.[72] Melanin is able to effectively chelate metal ions through its carboxylate and phenolic hydroxyl groups, in many cases much more efficiently than the powerful chelating ligand ethylenediaminetetraacetate (EDTA). Thus, it may serve to sequester potentially toxic metal ions, protecting the rest of the cell. This hypothesis is supported by the fact that the loss of neuromelanin observed in Parkinson's disease is accompanied by an increase in iron levels in the brain.

Physical properties and technological applications

Evidence exists in support of a highly cross-linked

downregulation of rod outer segment phagocytosis by the RPE. This phenomenon has been attributed in part to foveal sparing in macular degeneration.[76]

Role in melanoma metastasis

The research done by Sarna's team proved that heavily pigmented melanoma cells have Young's modulus about 4.93 kPa, when in non-pigmented ones it was only 0.98 kPa.[77] In another experiment they found that elasticity of melanoma cells is important for its metastasis and growth: non-pigmented tumors were bigger than pigmented and it was much easier for them to spread. They also showed that there are both pigmented and non-pigmented cells in melanoma tumors, so that they can both be drug-resistant and metastatic.[77]

See also

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External links

Look up melanin in Wiktionary, the free dictionary.
Look up leuco form in Wiktionary, the free dictionary.
Retrieved from "https://en.wikipedia.org/w/index.php?title=Melanin&oldid=1217727298#Eumelanin"