Melanin
Encyclopedia
Melanin is a pigment
that is ubiquitous in nature, being found in most organisms (spider
s are one of the few groups in which it has not been detected). In animals melanin pigments are derivatives of the amino acid tyrosine
. The most common form of biological
melanin is eumelanin, a brown-black polymer
of dihydroxyindole
carboxylic acid
s, and their reduced forms. All melanins can be considered as derivatives of polyacetylene
, since they rely on a polyconiugate structure. Another common form of melanin is pheomelanin, a red-brown polymer
of benzothiazine
units largely responsible for red hair and freckles. The presence of melanin in the archaea
and bacteria
kingdoms is an issue of ongoing debate among researchers in the field.
The increased production of melanin in human skin is called melanogenesis. Production of melanin is stimulated by DNA damage induced by UVB-radiation, and it leads to a delayed development of a tan. This melanogenesis-based tan takes more time to develop, but it is long-lasting.
The photochemical properties of melanin make it an excellent photoprotectant
. It absorbs harmful UV-radiation (ultraviolet) and transforms the energy into harmless heat through a process called "ultrafast internal conversion
". This property enables melanin to dissipate more than 99.9% of the absorbed UV radiation as heat (see photoprotection
). This prevents the indirect DNA damage
that is responsible for the formation of malignant melanoma and other skin cancers.
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 zona reticularis
of the adrenal gland
, and pigment-bearing neurons within areas of the brainstem, such as the locus coeruleus and the substantia nigra
.
The melanin in the skin is produced by melanocyte
s, which are found in the basal layer
of the epidermis. Although, in general, human beings possess a similar concentration of melanocytes in their skin, the melanocytes in some individuals and ethnic groups more frequently or less frequently express
the melanin-producing gene
s, thereby conferring a greater or lesser concentration of skin melanin. Some individual animals and humans have very little or no melanin in their bodies, a condition known as albinism
.
Because melanin is an aggregate of smaller component molecules, there are many different types of melanin with differing 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
.
s have long been thought to comprise numerous cross-linked 5,6-dihydroxyindole
(DHI) and 5,6-dihydroxyindole-2-carboxylic acid
(DHICA) polymers. However, recent research into the electrical properties of eumelanin has indicated that it may consist of more basic oligomer
s adhering to one another by some other mechanism. Eumelanin is found in hair, areola
, and skin, and the hair colors grey, black, yellow, and brown. In humans, it is more abundant in people with dark skin.
There are two different types of eumelanin. The two types are black eumelanin and brown eumelanin, with black melanin being darker than brown. Black eumelanin is mostly in non-Europeans and aged Europeans, while brown eumelanin is in mostly young Europeans.
A small amount of black eumelanin in the absence of other pigments causes grey hair. A small amount of brown eumelanin in the absence of other pigments causes yellow (blond) color hair.
. Pheomelanin also may become carcinogen
ic when exposed to the ultraviolet rays of the sun. In chemical terms, pheomelanin differs from eumelanin in that its oligomer structure incorporates benzothiazine
and benzothiazole
units that are produced, instead of DHI and DHICA, when the amino acid L-cysteine is present.
(from the Latin
black substance) - Pars Compacta part, the locus coeruleus (blue spot), the dorsal motor nucleus of the vagus nerve
(cranial nerve X), and the median raphe nucleus of the pons
. Both the substantia nigra
and locus coeruleus can be easily identified grossly at the time of autopsy because of their dark pigmentation. In human
s, these nuclei are not pigmented at the time of birth, but develop pigmentation during maturation to adulthood.
Although the functional nature of neuromelanin is unknown in the brain, the pigment is made from oxyradical metabolites of monoamine neurotransmitter
s including dopamine
and norepinephrine
. Luigi Zecca and David Sulzer
demonstrated that neuromelanin pigment is an autophagy
product that accumulates in lysosomes, which are unable to effectively degrade it. In this way, the synthesis of neuromelanin, is protective as its encapsulation within the autophagic organelle removes it from reacting with sites in the neuronal cytosol that could lead to neurotoxicity.
While neuromelanin becomes higher throughout life in most people, the loss of pigmented neurons from specific nuclei is seen in a variety of neurodegenerative diseases. In Parkinson's disease
there is massive loss of dopamine
-producing pigmented neurons in the substantia nigra
. High levels of neuromelanin are also detected in other primate
s, and in carnivore
s such as cat
s and dog
s.
s (see cephalopod ink
) as a defense mechanism against predators. Melanins also protect microorganisms, such as bacteria and fungi, against stresses that involve cell damage such as UV radiation from the sun and reactive oxygen species
. Melanin also protects against damage from high temperatures, chemical stresses (such as heavy metals
and oxidizing agents), and biochemical threats (such as host defenses against invading microbes). Therefore, in many pathogenic microbes (for example, in Cryptococcus neoformans
, a fungus) melanins appear to play important roles in virulence
and pathogenicity
by protecting the microbe against immune
responses of its host
. In invertebrates, a major aspect of the innate immune defense system against invading pathogens involves melanin. Within minutes after infection, the microbe is encapsulated within melanin (melanization), and the generation of free radical byproducts during the formation of this capsule is thought to aid in killing them. Some types of fungi, called radiotrophic fungi
, appear to be able to use melanin as a photosynthetic pigment that enables them to capture gamma rays and harness its energy for growth.
The black feathers of birds owe their color to melanin; they are much more readily degraded by bacteria than white feathers, or those containing other pigments such as carotene
s.
Catechol melanin
s are plant melanins.
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The first step of the biosynthetic pathway for both eumelanins and pheomelanins is catalysed
by tyrosinase
:
Dopaquinone can combine with cysteine
by two pathways to benzothiazines and pheomelanins
Alternatively, dopaquinone can be converted to leucodopachrome and follow two more pathways to the eumelanins
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.
There are approximately ten different types of oculocutaneous albinism
, which is mostly an autosomal recessive disorder. Certain ethnicities have higher incidences of different forms. For example, the most common type, called oculocutaneous albinism type 2 (OCA2), is especially frequent among people of black Africa
n descent. It is an autosomal recessive disorder characterized by a 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. In some African nations, the frequency of the disorder is even higher, ranging from 1 in 2,000 to 1 in 5,000. 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.
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 2700 most prevalent among people of Puerto Rican origin, are associated with mortality beyond melanoma-related deaths.
The role that melanin deficiency plays in such disorders remains under study.
The connection between albinism and deafness is well known, though poorly understood. E.g., in his 1859 treatise On the Origin of Species, Charles Darwin
observed that "cats which are entirely white and have blue eyes are generally deaf". In humans, hypopigmentation and deafness occur together in the rare Waardenburg's syndrome, predominantly observed among the Hopi
in North America
. The incidence of albinism in Hopi Indians has been estimated as approximately 1 in 200 individuals. It is interesting to note that similar patterns of albinism and deafness have been found in other mammals, including dogs and rodents. However, a lack of melanin per se does not appear to be directly responsible for deafness associated with hypopigmentation, as most individuals lacking the enzymes required to synthesize melanin have normal auditory function. Instead the absence of melanocytes in the stria vascularis of the inner ear results in cochlea
r impairment, though why this is, is not fully understood. It may be that melanin, the best sound-absorbing material known, plays some protective function. in alternate fashion, melanin may affect development, as Darwin suggests.
In Parkinson's disease
, a disorder that affects neuromotor functioning, there is decreased neuromelanin in the substantia nigra as consequence of specific dropping out of dopaminergic pigmented neurons. This results in diminished dopamine
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.". Also see Nicolaus review article on the function of neuromelanins
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 protein
s, 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
.
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 stain
s. 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 similar manner, melanin can complicate laser treatment of other dermatological conditions in people with darker skin.
Freckles and mole
s 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 and nicotine. This has been suggested to underlie the increased nicotine dependence and lower smoking cessation
rates in darker pigmented individuals.
called melanosome
s. These are then transferred into the other skin cells of the human 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 results in melanoma
s in lighter-skinned people.
With humans, exposure to sunlight stimulates the skin
to produce vitamin D
. Because high levels of cutaneous melanin act as a natural sun screen, dark skin can be a risk factor for vitamin D deficiency in regions of the Earth known as cool temperate zones, i.e., above 36 degrees latitude in the Northern hemisphere and below 36 degrees in the Southern hemisphere. As a result of this, health authorities in Canada and the USA have issued recommendations for people with darker complexions (including people of southern European descent) to consume between 1000-2000 IU (International Units) of vitamin D, daily, through Autumn to Spring.
The most recent scientific evidence indicates that all humans evolved in Africa
, then populated the rest of the world through successive radiations. It seems likely that the first modern humans had relatively large numbers of eumelanin-producing melanocytes. In accordance, they had darker skin as with the indigenous people of Africa today. As some of these original peoples migrated and settled in areas of Asia
and Europe
, the selective pressure for eumelanin production decreased in climates where radiation from the sun was less intense. Of the two common gene variants known to be associated with pale human skin, Mc1r does not appear to have undergone positive selection, while SLC24A5
has.
As with peoples having migrated northward, those with light skin migrating toward the equator acclimatize to the much stronger solar radiation. Most people's skin darkens when exposed to UV light, giving them more protection when it is needed. This is the physiological purpose of sun tanning
. Dark-skinned people, who produce more skin-protecting eumelanin, have a greater protection against sunburn
and the development of melanoma
, a potentially deadly form of skin cancer
, as well as other health problems related to exposure to strong solar radiation, including the photodegradation
of certain vitamin
s such as riboflavin
s, carotenoid
s, tocopherol
, and folate.
Melanin in the eyes, in the iris
and choroid
, helps protect them from ultraviolet
and high-frequency visible light; people with gray, blue, and green eyes
are more at risk for sun-related eye problems. Further, the ocular lens yellows with age, providing added protection. However, the lens also becomes more rigid with age, losing most of its 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 by J.D. Simon et al. suggests that melanin may serve a protective role other than photoprotection. Melanin is able to effectively ligate
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.
, polypyrrole
, and polyaniline
"Blacks" and their mixed copolymers. The simplest melanin is polyacetylene, and some fungal melanins are pure polyacetylene.
In 1963, D.E Weiss and coworkers reported high electrical conductivity in a melanin, iodine-doped and oxidized polypyrrole
"Black". They achieved the quite high conductivity of 1 Ohm/cm. A decade later, John McGinness
, and coworkers reported a high conductivity "ON" state in a voltage-controlled solid-state threshold switch made with DOPA melanin. Further, this material emitted a flash of light—electroluminescence
—when it switched. Melanin also shows negative resistance
, a classic property of electronically-active conductive polymers. Likewise, melanin is the best sound-absorbing material known, because of its strong electron-phonon
coupling. This might explain part of the reason behind melanin's presence in the inner ear
.
These early discoveries were "lost" until the recent emergence of such melanins in device applications, in particular, electroluminescent displays. In 2000, the Nobel Prize
in Chemistry was awarded to three scientists for their subsequent 1977 (re)discovery and development of such conductive organic polymers. In an essential reprise of the work by Weiss et al., these polymers were oxidized, iodine-doped "polyacetylene
black" melanins. There is no evidence that the Nobel committee was aware of the almost identical prior report by Weiss et al. of passive high conductivity in iodinated polypyrrole black or of switching and high electrical conductivity in DOPA melanin and related organic semiconductor
s. The melanin organic electronic device is now in the Smithsonian Institution
's National Museum of American History
's "Smithsonian Chips", collection of historic solid-state electronic devices.
Although synthetic melanin (commonly referred to as BSM, or "black synthetic matter") is made up of 3-6 oligomeric units linked together — the so-called "protomolecule" — there is no evidence that naturally occurring biopolymer (BCM, for "black cell matter") mimics this structure. However, since there is no reason to believe that natural melanin does not belong to the category of the polyarenes and polycationic polyenes, like pyrrol black and acetylene black, it is necessary to review all the chemical and biological analytic data gathered to date in the study of natural melanins (eumelanins, pheomelanins, allomelanins)."
Evidence exists in support of a highly cross-linked heteropolymer
bound covalently
to matrix scaffolding melanoproteins. It has been proposed that the ability of melanin to act as an antioxidant
is directly proportional to its degree of polymerization or molecular weight. Suboptimal conditions for the effective polymerization of melanin monomer
s may lead to formation of lower-molecular-weight, pro-oxidant melanin that has been implicated in the causation and progression of macular degeneration
and melanoma
. Signaling pathway
s that upregulate melanization in the retinal pigment epithelium (RPE) also may be implicated in the downregulation of rod
outer segment phagocytosis by the RPE. This phenomenon has been attributed in part to fovea
l sparing in macular degeneration
.
The act of placing skin pigmentation within a rubric of racial classification and linked to social status or other human attributes is known as racialism
. Many people and societies overlay racialism with racist
perceptions and systems that arbitrarily assign to groups of people sharing a genetically transmitted pigmentation a status of inherent superiority or inferiority, privilege, or disadvantage based on skin color.
Apartheid-era South Africa
is an example of a white supremacist
society based on a system of stratification of power and privilege by skin color, as well as racial admixture. Similar examples can be found in Brazil
's highly socially color-stratified society; and, in the U.S., segregation
, institutional racism
, and internal "color consciousness" on the part of members of some ethnicities.
Pigment
A pigment is a material that changes the color of reflected or transmitted light as the result of wavelength-selective absorption. This physical process differs from fluorescence, phosphorescence, and other forms of luminescence, in which a material emits light.Many materials selectively absorb...
that is ubiquitous in nature, being found in most organisms (spider
Spider
Spiders are air-breathing arthropods that have eight legs, and chelicerae with fangs that inject venom. They are the largest order of arachnids and rank seventh in total species diversity among all other groups of organisms...
s are one of the few groups in which it has not been detected). In animals melanin pigments are derivatives of the amino acid tyrosine
Tyrosine
Tyrosine or 4-hydroxyphenylalanine, is one of the 22 amino acids that are used by cells to synthesize proteins. Its codons are UAC and UAU. It is a non-essential amino acid with a polar side group...
. The most common form of biological
Biological tissue
Tissue is a cellular organizational level intermediate between cells and a complete organism. A tissue is an ensemble of cells, not necessarily identical, but from the same origin, that together carry out a specific function. These are called tissues because of their identical functioning...
melanin is eumelanin, a brown-black polymer
Polymer
A polymer is a large molecule composed of repeating structural units. These subunits are typically connected by covalent chemical bonds...
of dihydroxyindole
Indole
Indole is an aromatic heterocyclic organic compound. It has a bicyclic structure, consisting of a six-membered benzene ring fused to a five-membered nitrogen-containing pyrrole ring. Indole is a popular component of fragrances and the precursor to many pharmaceuticals. Compounds that contain an...
carboxylic acid
Carboxylic acid
Carboxylic acids are organic acids characterized by the presence of at least one carboxyl group. The general formula of a carboxylic acid is R-COOH, where R is some monovalent functional group...
s, and their reduced forms. All melanins can be considered as derivatives of polyacetylene
Polyacetylene
Polyacetylene is an organic polymer with the repeat unit n. The high electrical conductivity discovered for these polymers beginning in the 1960's accelerated interest in the use of organic compounds in microelectronics...
, since they rely on a polyconiugate structure. Another common form of melanin is pheomelanin, a red-brown polymer
Polymer
A polymer is a large molecule composed of repeating structural units. These subunits are typically connected by covalent chemical bonds...
of benzothiazine
Benzothiazine
Benzothiazine is a heterocyclic compound consisting of a benzene ring attached to the 6-membered heterocycle thiazine. The name is applied to both the 2H- and 4H- isomers of the molecule....
units largely responsible for red hair and freckles. The presence of melanin in the archaea
Archaea
The Archaea are a group of single-celled microorganisms. A single individual or species from this domain is called an archaeon...
and bacteria
Bacteria
Bacteria are a large domain of prokaryotic microorganisms. Typically a few micrometres in length, bacteria have a wide range of shapes, ranging from spheres to rods and spirals...
kingdoms is an issue of ongoing debate among researchers in the field.
The increased production of melanin in human skin is called melanogenesis. Production of melanin is stimulated by DNA damage induced by UVB-radiation, and it leads to a delayed development of a tan. This melanogenesis-based tan takes more time to develop, but it is long-lasting.
The photochemical properties of melanin make it an excellent photoprotectant
Photoprotection
Photoprotection is a group of mechanisms that nature has developed to minimize the damage that the human body suffers when exposed to UV radiation...
. It absorbs harmful UV-radiation (ultraviolet) and transforms the energy into harmless heat through a process called "ultrafast internal conversion
Internal conversion (chemistry)
Internal conversion is a transition from a higher to a lower electronic state in a molecule or atom. It is sometimes called "radiationless de-excitation", because no photons are emitted...
". This property enables melanin to dissipate more than 99.9% of the absorbed UV radiation as heat (see photoprotection
Photoprotection
Photoprotection is a group of mechanisms that nature has developed to minimize the damage that the human body suffers when exposed to UV radiation...
). This prevents the indirect DNA damage
Indirect DNA damage
Indirect DNA damage occurs when a UV-photon is absorbed in the human skin by a chromophore that does not have the ability to convert the energy into harmless heat very quickly. Molecules that do not have this ability have a long lived excited state. This long lifetime leads to a high probability...
that is responsible for the formation of malignant melanoma and other skin cancers.
In humans
Human skin color
Human skin color is primarily due to the presence of melanin in the skin. Skin color ranges from almost black to white with a pinkish tinge due to blood vessels underneath. Variation in natural skin color is mainly due to genetics, although the evolutionary causes are not completely certain...
. It is also found in hair
Hair
Hair is a filamentous biomaterial, that grows from follicles found in the dermis. Found exclusively in mammals, hair is one of the defining characteristics of the mammalian class....
, the pigmented tissue underlying the iris
Iris (anatomy)
The iris is a thin, circular structure in the eye, responsible for controlling the diameter and size of the pupils and thus the amount of light reaching the retina. "Eye color" is the color of the iris, which can be green, blue, or brown. In some cases it can be hazel , grey, violet, or even pink...
of the eye, and the stria vascularis of the inner ear
Inner ear
The inner ear is the innermost part of the vertebrate ear. In mammals, it consists of the bony labyrinth, a hollow cavity in the temporal bone of the skull with a system of passages comprising two main functional parts:...
. In the brain, tissues with melanin include the medulla
Adrenal medulla
The adrenal medulla is part of the adrenal gland. It is located at the center of the gland, being surrounded by the adrenal cortex. It is the innermost part of the adrenal gland, consisting of cells that secrete epinephrine , norepinephrine , and a small amount of dopamine in response to...
and zona reticularis
Zona reticularis
The zona reticularis is the innermost layer of the adrenal cortex, lying deep to the zona fasciculata and superficial to the adrenal medulla. The cells are arranged cords that project in different directions giving a net-like appearance The zona reticularis is the innermost layer of the adrenal...
of the adrenal gland
Adrenal gland
In mammals, the adrenal glands are endocrine glands that sit atop the kidneys; in humans, the right suprarenal gland is triangular shaped, while the left suprarenal gland is semilunar shaped...
, and pigment-bearing neurons within areas of the brainstem, such as the locus coeruleus and the substantia nigra
Substantia nigra
The substantia nigra is a brain structure located in the mesencephalon that plays an important role in reward, addiction, and movement. Substantia nigra is Latin for "black substance", as parts of the substantia nigra appear darker than neighboring areas due to high levels of melanin in...
.
The melanin in the skin is produced by melanocyte
Melanocyte
-External links: - "Eye: fovea, RPE" - "Integument: pigmented skin"...
s, which are found in the basal layer
Stratum germinativum
The stratum basale is the deepest layer of the five layers of the epidermis, which is the outer covering of skin in mammals. The stratum basale is a continuous layer of cells...
of the epidermis. Although, in general, human beings possess a similar concentration of melanocytes in their skin, the melanocytes in some individuals and ethnic groups more frequently or less frequently express
Gene expression
Gene expression is the process by which information from a gene is used in the synthesis of a functional gene product. These products are often proteins, but in non-protein coding genes such as ribosomal RNA , transfer RNA or small nuclear RNA genes, the product is a functional RNA...
the melanin-producing gene
Gene
A gene is a molecular unit of heredity of a living organism. It is a name given to some stretches of DNA and RNA that code for a type of protein or for an RNA chain that has a function in the organism. Living beings depend on genes, as they specify all proteins and functional RNA chains...
s, thereby conferring a greater or lesser concentration of skin melanin. Some individual animals and humans have very little or no melanin in their bodies, a condition known as albinism
Albinism
Albinism is a congenital disorder characterized by the complete or partial absence of pigment in the skin, hair and eyes due to absence or defect of an enzyme involved in the production of melanin...
.
Because melanin is an aggregate of smaller component molecules, there are many different types of melanin with differing proportions and bonding patterns of these component molecules. Both pheomelanin and eumelanin are found in human skin and hair
Hair
Hair is a filamentous biomaterial, that grows from follicles found in the dermis. Found exclusively in mammals, hair is one of the defining characteristics of the mammalian class....
, but eumelanin is the most abundant melanin in humans, as well as the form most likely to be deficient in albinism
Albinism
Albinism is a congenital disorder characterized by the complete or partial absence of pigment in the skin, hair and eyes due to absence or defect of an enzyme involved in the production of melanin...
.
Eumelanin
Eumelanin polymerPolymer
A polymer is a large molecule composed of repeating structural units. These subunits are typically connected by covalent chemical bonds...
s have long been thought to comprise numerous cross-linked 5,6-dihydroxyindole
Indole
Indole is an aromatic heterocyclic organic compound. It has a bicyclic structure, consisting of a six-membered benzene ring fused to a five-membered nitrogen-containing pyrrole ring. Indole is a popular component of fragrances and the precursor to many pharmaceuticals. Compounds that contain an...
(DHI) and 5,6-dihydroxyindole-2-carboxylic acid
Carboxylic acid
Carboxylic acids are organic acids characterized by the presence of at least one carboxyl group. The general formula of a carboxylic acid is R-COOH, where R is some monovalent functional group...
(DHICA) polymers. However, recent research into the electrical properties of eumelanin has indicated that it may consist of more basic oligomer
Oligomer
In chemistry, an oligomer is a molecule that consists of a few monomer units , in contrast to a polymer that, at least in principle, consists of an unlimited number of monomers. Dimers, trimers, and tetramers are oligomers. Many oils are oligomeric, such as liquid paraffin...
s adhering to one another by some other mechanism. Eumelanin is found in hair, areola
Areola
This article is about the breast tissue. For the entomology term, see the glossary of Lepidopteran terms. For an artistic cloud motif, see aureola. For the cactus feature, see Areole....
, and skin, and the hair colors grey, black, yellow, and brown. In humans, it is more abundant in people with dark skin.
There are two different types of eumelanin. The two types are black eumelanin and brown eumelanin, with black melanin being darker than brown. Black eumelanin is mostly in non-Europeans and aged Europeans, while brown eumelanin is in mostly young Europeans.
A small amount of black eumelanin in the absence of other pigments causes grey hair. A small amount of brown eumelanin in the absence of other pigments causes yellow (blond) color hair.
Pheomelanin
Pheomelanin is also found in hair and skin and is both in lighter-skinned humans and darker-skinned humans. Pheomelanin imparts a pink to red hue and, thus, is found in particularly large quantities in red hairRed hair
Red hair occurs on approximately 1–2% of the human population. It occurs more frequently in people of northern or western European ancestry, and less frequently in other populations...
. Pheomelanin also may become carcinogen
Carcinogen
A carcinogen is any substance, radionuclide, or radiation that is an agent directly involved in causing cancer. This may be due to the ability to damage the genome or to the disruption of cellular metabolic processes...
ic when exposed to the ultraviolet rays of the sun. In chemical terms, pheomelanin differs from eumelanin in that its oligomer structure incorporates benzothiazine
Benzothiazine
Benzothiazine is a heterocyclic compound consisting of a benzene ring attached to the 6-membered heterocycle thiazine. The name is applied to both the 2H- and 4H- isomers of the molecule....
and benzothiazole
Benzothiazole
Benzothiazole is an aromatic heterocyclic compound with the chemical formula . It is colorless, slightly viscous liquid. Although the parent compound, benzothiazole is not widely used, many of its derivatives are found in commercial products or in nature...
units that are produced, instead of DHI and DHICA, when the amino acid L-cysteine is present.
Neuromelanin
Neuromelanin is the dark pigment present in pigment-bearing neurons of four deep brain nuclei: the substantia nigraSubstantia nigra
The substantia nigra is a brain structure located in the mesencephalon that plays an important role in reward, addiction, and movement. Substantia nigra is Latin for "black substance", as parts of the substantia nigra appear darker than neighboring areas due to high levels of melanin in...
(from the Latin
Latin
Latin is an Italic language originally spoken in Latium and Ancient Rome. It, along with most European languages, is a descendant of the ancient Proto-Indo-European language. Although it is considered a dead language, a number of scholars and members of the Christian clergy speak it fluently, and...
black substance) - Pars Compacta part, the locus coeruleus (blue spot), the dorsal motor nucleus of the vagus nerve
Vagus nerve
The vagus nerve , also called pneumogastric nerve or cranial nerve X, is the tenth of twelve paired cranial nerves...
(cranial nerve X), and the median raphe nucleus of the pons
Pons
The pons is a structure located on the brain stem, named after the Latin word for "bridge" or the 16th-century Italian anatomist and surgeon Costanzo Varolio . It is superior to the medulla oblongata, inferior to the midbrain, and ventral to the cerebellum. In humans and other bipeds this means it...
. Both the substantia nigra
Substantia nigra
The substantia nigra is a brain structure located in the mesencephalon that plays an important role in reward, addiction, and movement. Substantia nigra is Latin for "black substance", as parts of the substantia nigra appear darker than neighboring areas due to high levels of melanin in...
and locus coeruleus can be easily identified grossly at the time of autopsy because of their dark pigmentation. In human
Human
Humans are the only living species in the Homo genus...
s, these nuclei are not pigmented at the time of birth, but develop pigmentation during maturation to adulthood.
Although the functional nature of neuromelanin is unknown in the brain, the pigment is made from oxyradical metabolites of monoamine neurotransmitter
Monoamine neurotransmitter
thumb|right|350px| A phylogenetic tree showing how a number of monoamine receptors are related to each other.Monoamine neurotransmitters are neurotransmitters and neuromodulators that contain one amino group that is connected to an aromatic ring by a two-carbon chain...
s including dopamine
Dopamine
Dopamine is a catecholamine neurotransmitter present in a wide variety of animals, including both vertebrates and invertebrates. In the brain, this substituted phenethylamine functions as a neurotransmitter, activating the five known types of dopamine receptors—D1, D2, D3, D4, and D5—and their...
and norepinephrine
Norepinephrine
Norepinephrine is the US name for noradrenaline , a catecholamine with multiple roles including as a hormone and a neurotransmitter...
. Luigi Zecca and David Sulzer
David Sulzer
David Sulzer is a American neuroscientist and Professor at Columbia University Medical Center in the Departments of Psychiatry, Neurology, and Pharmacology...
demonstrated that neuromelanin pigment is an autophagy
Autophagy
In cell biology, autophagy, or autophagocytosis, is a catabolic process involving the degradation of a cell's own components through the lysosomal machinery. It is a tightly regulated process that plays a normal part in cell growth, development, and homeostasis, helping to maintain a balance...
product that accumulates in lysosomes, which are unable to effectively degrade it. In this way, the synthesis of neuromelanin, is protective as its encapsulation within the autophagic organelle removes it from reacting with sites in the neuronal cytosol that could lead to neurotoxicity.
While neuromelanin becomes higher throughout life in most people, the loss of pigmented neurons from specific nuclei is seen in a variety of neurodegenerative diseases. In Parkinson's disease
Parkinson's disease
Parkinson's disease is a degenerative disorder of the central nervous system...
there is massive loss of dopamine
Dopamine
Dopamine is a catecholamine neurotransmitter present in a wide variety of animals, including both vertebrates and invertebrates. In the brain, this substituted phenethylamine functions as a neurotransmitter, activating the five known types of dopamine receptors—D1, D2, D3, D4, and D5—and their...
-producing pigmented neurons in the substantia nigra
Substantia nigra
The substantia nigra is a brain structure located in the mesencephalon that plays an important role in reward, addiction, and movement. Substantia nigra is Latin for "black substance", as parts of the substantia nigra appear darker than neighboring areas due to high levels of melanin in...
. High levels of neuromelanin are also detected in other primate
Primate
A primate is a mammal of the order Primates , which contains prosimians and simians. Primates arose from ancestors that lived in the trees of tropical forests; many primate characteristics represent adaptations to life in this challenging three-dimensional environment...
s, and in carnivore
Carnivore
A carnivore meaning 'meat eater' is an organism that derives its energy and nutrient requirements from a diet consisting mainly or exclusively of animal tissue, whether through predation or scavenging...
s such as cat
Cat
The cat , also known as the domestic cat or housecat to distinguish it from other felids and felines, is a small, usually furry, domesticated, carnivorous mammal that is valued by humans for its companionship and for its ability to hunt vermin and household pests...
s and dog
Dog
The domestic dog is a domesticated form of the gray wolf, a member of the Canidae family of the order Carnivora. The term is used for both feral and pet varieties. The dog may have been the first animal to be domesticated, and has been the most widely kept working, hunting, and companion animal in...
s.
In other organisms
Melanins have very diverse roles and functions in various organisms. A form of melanin makes up the ink used by many cephalopodCephalopod
A cephalopod is any member of the molluscan class Cephalopoda . These exclusively marine animals are characterized by bilateral body symmetry, a prominent head, and a set of arms or tentacles modified from the primitive molluscan foot...
s (see cephalopod ink
Cephalopod ink
Cephalopod ink is a dark pigment released into water by most species of cephalopod, usually as an escape mechanism. All cephalopods, with the exception of the Nautilidae and the species of octopus belonging to the suborder Cirrina, are able to release ink....
) as a defense mechanism against predators. Melanins also protect microorganisms, such as bacteria and fungi, against stresses that involve cell damage such as UV radiation from the sun and reactive oxygen species
Reactive oxygen species
Reactive oxygen species are chemically reactive molecules containing oxygen. Examples include oxygen ions and peroxides. Reactive oxygen species are highly reactive due to the presence of unpaired valence shell electrons....
. Melanin also protects against damage from high temperatures, chemical stresses (such as heavy metals
Heavy metals
A heavy metal is a member of a loosely-defined subset of elements that exhibit metallic properties. It mainly includes the transition metals, some metalloids, lanthanides, and actinides. Many different definitions have been proposed—some based on density, some on atomic number or atomic weight,...
and oxidizing agents), and biochemical threats (such as host defenses against invading microbes). Therefore, in many pathogenic microbes (for example, in Cryptococcus neoformans
Cryptococcus neoformans
Cryptococcus neoformans is an encapsulated yeast that can live in both plants and animals. Its teleomorph is Filobasidiella neoformans, a filamentous fungus belonging to the class Tremellomycetes. It is often found in pigeon excrement....
, a fungus) melanins appear to play important roles in virulence
Virulence
Virulence is by MeSH definition the degree of pathogenicity within a group or species of parasites as indicated by case fatality rates and/or the ability of the organism to invade the tissues of the host. The pathogenicity of an organism - its ability to cause disease - is determined by its...
and pathogenicity
Pathogenicity
Pathogenicity is the ability of a pathogen to produce an infectious disease in an organism.It is often used interchangeably with the term "virulence", although virulence is used more specifically to describe the relative degree of damage done by a pathogen, or the degree of pathogenicity caused by...
by protecting the microbe against immune
Immune system
An immune system is a system of biological structures and processes within an organism that protects against disease by identifying and killing pathogens and tumor cells. It detects a wide variety of agents, from viruses to parasitic worms, and needs to distinguish them from the organism's own...
responses of its host
Host (biology)
In biology, a host is an organism that harbors a parasite, or a mutual or commensal symbiont, typically providing nourishment and shelter. In botany, a host plant is one that supplies food resources and substrate for certain insects or other fauna...
. In invertebrates, a major aspect of the innate immune defense system against invading pathogens involves melanin. Within minutes after infection, the microbe is encapsulated within melanin (melanization), and the generation of free radical byproducts during the formation of this capsule is thought to aid in killing them. Some types of fungi, called radiotrophic fungi
Radiotrophic fungus
Radiotrophic fungi are fungi which appear to use the pigment melanin to convert gamma radiation into chemical energy for growth. This proposed mechanism may be similar to anabolic pathways for the synthesis of reduced organic carbon in phototrophic organisms, which capture photons from visible...
, appear to be able to use melanin as a photosynthetic pigment that enables them to capture gamma rays and harness its energy for growth.
The black feathers of birds owe their color to melanin; they are much more readily degraded by bacteria than white feathers, or those containing other pigments such as carotene
Carotene
The term carotene is used for several related unsaturated hydrocarbon substances having the formula C40Hx, which are synthesized by plants but cannot be made by animals. Carotene is an orange photosynthetic pigment important for photosynthesis. Carotenes are all coloured to the human eye...
s.
Catechol melanin
Catechol melanin
Catechol melanins are plant melanins. They yield catechol on alkali fusion. This type of substance can be found in fungi like Ustilago. Indole-5,6-quinone is a chemical compound found in the oxidative browning reaction of fruits like bananas mediated by polyphenol oxidase from tyrosine and...
s are plant melanins.
Biosynthetic pathways
The first step of the biosynthetic pathway for both eumelanins and pheomelanins is catalysed
Enzyme catalysis
Enzyme catalysis is the catalysis of chemical reactions by specialized proteins known as enzymes. Catalysis of biochemical reactions in the cell is vital due to the very low reaction rates of the uncatalysed reactions....
by tyrosinase
Tyrosinase
Tyrosinase also known as monophenol monooxygenase is an enzyme that catalyses the oxidation of phenols and is widespread in plants and animals...
:
- TyrosineTyrosineTyrosine or 4-hydroxyphenylalanine, is one of the 22 amino acids that are used by cells to synthesize proteins. Its codons are UAC and UAU. It is a non-essential amino acid with a polar side group...
→ DOPA → dopaquinone
Dopaquinone can combine with cysteine
Cysteine
Cysteine is an α-amino acid with the chemical formula HO2CCHCH2SH. It is a non-essential amino acid, which means that it is biosynthesized in humans. Its codons are UGU and UGC. The side chain on cysteine is thiol, which is polar and thus cysteine is usually classified as a hydrophilic amino acid...
by two pathways to benzothiazines and pheomelanins
- Dopaquinone + cysteine → 5-S-cysteinyldopa → benzothiazine intermediate → pheomelanin
- Dopaquinone + cysteine → 2-S-cysteinyldopa → benzothiazine intermediate → pheomelanin
Alternatively, 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 → quinoneQuinoneA quinone is a class of organic compounds that are formally "derived from aromatic compounds [such as benzene or naphthalene] by conversion of an even number of –CH= groups into –C– groups with any necessary rearrangement of double bonds," resulting in "a fully conjugated cyclic dione structure."...
→ eumelanin
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
Hemosiderin
thumb|Hemosiderin image of a kidney viewed under a microscope. The brown areas represent hemosiderinHemosiderin or haemosiderin is an iron-storage complex. It is always found within cells and appears to be a complex of ferritin, denatured ferritin and other material...
, 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
Potassium permanganate
Potassium permanganate is an inorganic chemical compound with the formula KMnO4. It is a salt consisting of K+ and MnO4− ions. Formerly known as permanganate of potash or Condy's crystals, it is a strong oxidizing agent. It dissolves in water to give intensely purple solutions, the...
is an effective melanin bleach.
Genetic disorders and disease states
Melanin deficiency has been connected for some time with various genetic abnormalities and disease states.There are approximately ten different types of oculocutaneous albinism
Oculocutaneous albinism
Oculocutaneous albinism is a form of albinism involving the eyes , skin , and in rare instances, the hair as well.Four types of oculocutaneous albinism have been described, all caused by a disruption of melanin synthesis and all autosomal recessive disorders.Common Albinism requires genes from both...
, which is mostly an autosomal recessive disorder. Certain ethnicities have higher incidences of different forms. For example, the most common type, called oculocutaneous albinism type 2 (OCA2), is especially frequent among people of black Africa
Africa
Africa is the world's second largest and second most populous continent, after Asia. At about 30.2 million km² including adjacent islands, it covers 6% of the Earth's total surface area and 20.4% of the total land area...
n descent. It is an autosomal recessive disorder characterized by a 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. In some African nations, the frequency of the disorder is even higher, ranging from 1 in 2,000 to 1 in 5,000. Another form of Albinism, the "yellow oculocutaneous albinism", appears to be more prevalent among the Amish
Amish
The Amish , sometimes referred to as Amish Mennonites, are a group of Christian church fellowships that form a subgroup of the Mennonite churches...
, who are of primarily Swiss
Switzerland
Switzerland name of one of the Swiss cantons. ; ; ; or ), in its full name the Swiss Confederation , is a federal republic consisting of 26 cantons, with Bern as the seat of the federal authorities. The country is situated in Western Europe,Or Central Europe depending on the definition....
and German
Germany
Germany , officially the Federal Republic of Germany , is a federal parliamentary republic in Europe. The country consists of 16 states while the capital and largest city is Berlin. Germany covers an area of 357,021 km2 and has a largely temperate seasonal climate...
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.
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 2700 most prevalent among people of Puerto Rican origin, are associated with mortality beyond melanoma-related deaths.
Mortality also is increased in patients with Hermansky-Pudlak syndromeHermansky-Pudlak syndromeHermansky–Pudlak syndrome is a rare autosomal recessive disorder which results in oculocutaneous albinism , bleeding problems due to a platelet abnormality , and storage of an abnormal fat-protein compound .There are eight classic forms of the disorder, based on the genetic mutation...
and Chediak-Higashi syndromeChédiak-Higashi syndromeChédiak–Higashi syndrome is a rare autosomal recessive disorder that arises from a microtubule polymerization defect which leads to a decrease in phagocytosis. The decrease in phagocytosis results in recurrent pyogenic infections, partial albinism and peripheral neuropathy...
. Patients with Hermansky-Pudlak syndrome have a bleeding diathesis secondary to platelet dysfunction and also experience restrictive lung disease (pulmonary fibrosis), inflammatory bowel disease, cardiomyopathy, and renal disease. Patients with Chediak-Higashi syndrome are susceptible to infection and also can develop lymphofollicular malignancy.
The role that melanin deficiency plays in such disorders remains under study.
The connection between albinism and deafness is well known, though poorly understood. E.g., in his 1859 treatise On the Origin of Species, Charles Darwin
Charles Darwin
Charles Robert Darwin FRS was an English naturalist. He established that all species of life have descended over time from common ancestry, and proposed the scientific theory that this branching pattern of evolution resulted from a process that he called natural selection.He published his theory...
observed that "cats which are entirely white and have blue eyes are generally deaf". In humans, hypopigmentation and deafness occur together in the rare Waardenburg's syndrome, predominantly observed among the Hopi
Hopi
The Hopi are a federally recognized tribe of indigenous Native American people, who primarily live on the Hopi Reservation in northeastern Arizona. The Hopi area according to the 2000 census has a population of 6,946 people. Their Hopi language is one of the 30 of the Uto-Aztecan language...
in North America
North America
North America is a continent wholly within the Northern Hemisphere and almost wholly within the Western Hemisphere. It is also considered a northern subcontinent of the Americas...
. The incidence of albinism in Hopi Indians has been estimated as approximately 1 in 200 individuals. It is interesting to note that similar patterns of albinism and deafness have been found in other mammals, including dogs and rodents. However, a lack of melanin per se does not appear to be directly responsible for deafness associated with hypopigmentation, as most individuals lacking the enzymes required to synthesize melanin have normal auditory function. Instead the absence of melanocytes in the stria vascularis of the inner ear results in cochlea
Cochlea
The cochlea is the auditory portion of the inner ear. It is a spiral-shaped cavity in the bony labyrinth, making 2.5 turns around its axis, the modiolus....
r impairment, though why this is, is not fully understood. It may be that melanin, the best sound-absorbing material known, plays some protective function. in alternate fashion, melanin may affect development, as Darwin suggests.
In Parkinson's disease
Parkinson's disease
Parkinson's disease is a degenerative disorder of the central nervous system...
, a disorder that affects neuromotor functioning, there is decreased neuromelanin in the substantia nigra as consequence of specific dropping out of dopaminergic pigmented neurons. This results in diminished dopamine
Dopamine
Dopamine is a catecholamine neurotransmitter present in a wide variety of animals, including both vertebrates and invertebrates. In the brain, this substituted phenethylamine functions as a neurotransmitter, activating the five known types of dopamine receptors—D1, D2, D3, D4, and D5—and their...
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.". Also see Nicolaus review article on the function of neuromelanins
In addition to melanin deficiency, the molecular weight of the melanin polymer
Polymer
A polymer is a large molecule composed of repeating structural units. These subunits are typically connected by covalent chemical bonds...
may be decreased by various factors such as oxidative stress, exposure to light, perturbation in its association with melanosomal matrix protein
Matrix protein
Viral matrix proteins are non structural proteins linking the viral envelope with the virus core. They play a crucial role in virus assembly, and interact with the RNP complex as well as with the viral membrane...
s, changes in pH
PH
In chemistry, pH is a measure of the acidity or basicity of an aqueous solution. Pure water is said to be neutral, with a pH close to 7.0 at . Solutions with a pH less than 7 are said to be acidic and solutions with a pH greater than 7 are basic or alkaline...
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
Pro-oxidant
Pro-oxidants are chemicals that induce oxidative stress, through either creating reactive oxygen species or inhibiting antioxidant systems. The oxidative stress produced by these chemicals can damage cells and tissues...
. In its pro-oxidant state, melanin has been suggested to be involved in the causation and progression of macular degeneration
Macular degeneration
Age-related macular degeneration is a medical condition which usually affects older adults and results in a loss of vision in the center of the visual field because of damage to the retina. It occurs in “dry” and “wet” forms. It is a major cause of blindness and visual impairment in older adults...
and melanoma
Melanoma
Melanoma is a malignant tumor of melanocytes. Melanocytes are cells that produce the dark pigment, melanin, which is responsible for the color of skin. They predominantly occur in skin, but are also found in other parts of the body, including the bowel and the eye...
.
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 stain
Port-wine stain
A port-wine stain or naevus flammeus is a vascular anomaly consisting of superficial and deep dilated capillaries in the skin which produce a reddish to purplish discoloration of the skin. They are so called for their colour, resembling that of port wine...
s. 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 similar manner, melanin can complicate laser treatment of other dermatological conditions in people with darker skin.
Freckles and mole
Mole (skin marking)
A melanocytic nevus is a type of lesion that contains nevus cells .Some sources equate the term mole with "melanocytic nevus". Other sources reserve the term "mole" for other purposes....
s are formed where there is a localized concentration of melanin in the skin. They are highly associated with pale skin.
Nicotine
Nicotine
Nicotine is an alkaloid found in the nightshade family of plants that constitutes approximately 0.6–3.0% of the dry weight of tobacco, with biosynthesis taking place in the roots and accumulation occurring in the leaves...
has an affinity for melanin-containing tissues because of its precursor function in melanin synthesis or its irreversible binding of melanin and nicotine. This has been suggested to underlie the increased nicotine dependence and lower smoking cessation
Smoking cessation
Smoking cessation is the process of discontinuing the practice of inhaling a smoked substance. This article focuses exclusively on cessation of tobacco smoking; however, the methods described may apply to cessation of smoking other substances that can be difficult to stop using due to the...
rates in darker pigmented individuals.
Human adaptation
Melanocytes insert granules of melanin into specialized cellular vesiclesVesicle (biology)
A vesicle is a bubble of liquid within another liquid, a supramolecular assembly made up of many different molecules. More technically, a vesicle is a small membrane-enclosed sack that can store or transport substances. Vesicles can form naturally because of the properties of lipid membranes , or...
called melanosome
Melanosome
In a biological cell, a melanosome is an organelle containing melanin, the most common light-absorbing pigment found in the animal kingdom.Cells that synthesize melanins are called melanocytes, and also the retinal pigment epithelium cells, whereas cells that have merely engulfed the melanosomes...
s. These are then transferred into the other skin cells of the human epidermis. The melanosomes in each recipient cell accumulate atop the cell nucleus
Cell nucleus
In cell biology, the nucleus is a membrane-enclosed organelle found in eukaryotic cells. It contains most of the cell's genetic material, organized as multiple long linear DNA molecules in complex with a large variety of proteins, such as histones, to form chromosomes. The genes within these...
, where they protect the nuclear DNA
DNA
Deoxyribonucleic acid is a nucleic acid that contains the genetic instructions used in the development and functioning of all known living organisms . The DNA segments that carry this genetic information are called genes, but other DNA sequences have structural purposes, or are involved in...
from mutations caused by the ionizing radiation
Ionizing radiation
Ionizing radiation is radiation composed of particles that individually have sufficient energy to remove an electron from an atom or molecule. This ionization produces free radicals, which are atoms or molecules containing unpaired electrons...
of the sun's ultraviolet
Ultraviolet
Ultraviolet light is electromagnetic radiation with a wavelength shorter than that of visible light, but longer than X-rays, in the range 10 nm to 400 nm, and energies from 3 eV to 124 eV...
rays. In general, people whose ancestors lived for long periods in the regions of the globe near the equator
Equator
An equator is the intersection of a sphere's surface with the plane perpendicular to the sphere's axis of rotation and containing the sphere's center of mass....
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 results in melanoma
Melanoma
Melanoma is a malignant tumor of melanocytes. Melanocytes are cells that produce the dark pigment, melanin, which is responsible for the color of skin. They predominantly occur in skin, but are also found in other parts of the body, including the bowel and the eye...
s in lighter-skinned people.
With humans, exposure to sunlight stimulates the skin
Skin
-Dermis:The dermis is the layer of skin beneath the epidermis that consists of connective tissue and cushions the body from stress and strain. The dermis is tightly connected to the epidermis by a basement membrane. It also harbors many Mechanoreceptors that provide the sense of touch and heat...
to produce vitamin D
Vitamin D
Vitamin D is a group of fat-soluble secosteroids. In humans, vitamin D is unique both because it functions as a prohormone and because the body can synthesize it when sun exposure is adequate ....
. Because high levels of cutaneous melanin act as a natural sun screen, dark skin can be a risk factor for vitamin D deficiency in regions of the Earth known as cool temperate zones, i.e., above 36 degrees latitude in the Northern hemisphere and below 36 degrees in the Southern hemisphere. As a result of this, health authorities in Canada and the USA have issued recommendations for people with darker complexions (including people of southern European descent) to consume between 1000-2000 IU (International Units) of vitamin D, daily, through Autumn to Spring.
The most recent scientific evidence indicates that all humans evolved in Africa
Africa
Africa is the world's second largest and second most populous continent, after Asia. At about 30.2 million km² including adjacent islands, it covers 6% of the Earth's total surface area and 20.4% of the total land area...
, then populated the rest of the world through successive radiations. It seems likely that the first modern humans had relatively large numbers of eumelanin-producing melanocytes. In accordance, they had darker skin as with the indigenous people of Africa today. As some of these original peoples migrated and settled in areas of Asia
Asia
Asia is the world's largest and most populous continent, located primarily in the eastern and northern hemispheres. It covers 8.7% of the Earth's total surface area and with approximately 3.879 billion people, it hosts 60% of the world's current human population...
and Europe
Europe
Europe is, by convention, one of the world's seven continents. Comprising the westernmost peninsula of Eurasia, Europe is generally 'divided' from Asia to its east by the watershed divides of the Ural and Caucasus Mountains, the Ural River, the Caspian and Black Seas, and the waterways connecting...
, the selective pressure for eumelanin production decreased in climates where radiation from the sun was less intense. Of the two common gene variants known to be associated with pale human skin, Mc1r does not appear to have undergone positive selection, while SLC24A5
SLC24A5
Sodium/potassium/calcium exchanger 5 also known as solute carrier family 24 member 5 is a protein that in humans is encoded by the SLC24A5 gene that has a major influence on natural skin colour variation. The NCKX5 protein is a member of the potassium-dependent sodium/calcium exchanger family...
has.
As with peoples having migrated northward, those with light skin migrating toward the equator acclimatize to the much stronger solar radiation. Most people's skin darkens when exposed to UV light, giving them more protection when it is needed. This is the physiological purpose of sun tanning
Sun tanning
Sun tanning or simply tanning is the process whereby skin color is darkened or tanned. The process is most often a result of exposure to ultraviolet radiation from the sun or from artificial sources, such as a tanning bed, but can also be a result of windburn or reflected light...
. Dark-skinned people, who produce more skin-protecting eumelanin, have a greater protection against sunburn
Sunburn
A sunburn is a burn to living tissue, such as skin, which is produced by overexposure to ultraviolet radiation, commonly from the sun's rays. Usual mild symptoms in humans and other animals include red or reddish skin that is hot to the touch, general fatigue, and mild dizziness. An excess of UV...
and the development of melanoma
Melanoma
Melanoma is a malignant tumor of melanocytes. Melanocytes are cells that produce the dark pigment, melanin, which is responsible for the color of skin. They predominantly occur in skin, but are also found in other parts of the body, including the bowel and the eye...
, a potentially deadly form of skin cancer
Skin cancer
Skin neoplasms are skin growths with differing causes and varying degrees of malignancy. The three most common malignant skin cancers are basal cell cancer, squamous cell cancer, and melanoma, each of which is named after the type of skin cell from which it arises...
, as well as other health problems related to exposure to strong solar radiation, including the photodegradation
Photodegradation
Photodegradation is degradation of a photodegradable molecule caused by the absorption of photons, particularly those wavelengths found in sunlight, such as infrared radiation, visible light, and ultraviolet light. However, other forms of electromagnetic radiation can cause photodegradation...
of certain vitamin
Vitamin
A vitamin is an organic compound required as a nutrient in tiny amounts by an organism. In other words, an organic chemical compound is called a vitamin when it cannot be synthesized in sufficient quantities by an organism, and must be obtained from the diet. Thus, the term is conditional both on...
s such as riboflavin
Riboflavin
Riboflavin, also known as vitamin B2 or additive E101, is an easily absorbed micronutrient with a key role in maintaining health in humans and animals. It is the central component of the cofactors FAD and FMN, and is therefore required by all flavoproteins. As such, vitamin B2 is required for a...
s, carotenoid
Carotenoid
Carotenoids are tetraterpenoid organic pigments that are naturally occurring in the chloroplasts and chromoplasts of plants and some other photosynthetic organisms like algae, some bacteria, and some types of fungus. Carotenoids can be synthesized fats and other basic organic metabolic building...
s, tocopherol
Tocopherol
Tocopherols are a class of chemical compounds of which many have vitamin E activity. It is a series of organic compounds consisting of various methylated phenols...
, and folate.
Melanin in the eyes, in the iris
Iris (anatomy)
The iris is a thin, circular structure in the eye, responsible for controlling the diameter and size of the pupils and thus the amount of light reaching the retina. "Eye color" is the color of the iris, which can be green, blue, or brown. In some cases it can be hazel , grey, violet, or even pink...
and choroid
Choroid
The choroid, also known as the choroidea or choroid coat, is the vascular layer of the eye, containing connective tissue, and lying between the retina and the sclera. The human choroid is thickest at the far extreme rear of the eye , while in the outlying areas it narrows to 0.1 mm...
, helps protect them from ultraviolet
Ultraviolet
Ultraviolet light is electromagnetic radiation with a wavelength shorter than that of visible light, but longer than X-rays, in the range 10 nm to 400 nm, and energies from 3 eV to 124 eV...
and high-frequency visible light; people with gray, blue, and green eyes
Eye color
Eye color is a polygenic phenotypic character and is determined by two distinct factors: the pigmentation of the eye's iris and the frequency-dependence of the scattering of light by the turbid medium in the stroma of the iris....
are more at risk for sun-related eye problems. Further, the ocular lens yellows with age, providing added protection. However, the lens also becomes more rigid with age, losing most of its accommodation
Accommodation (eye)
Accommodation is the process by which the vertebrate eye changes optical power to maintain a clear image on an object as its distance changes....
— the ability to change shape to focus from far to near — a detriment due probably to protein
Protein
Proteins are biochemical compounds consisting of one or more polypeptides typically folded into a globular or fibrous form, facilitating a biological function. A polypeptide is a single linear polymer chain of amino acids bonded together by peptide bonds between the carboxyl and amino groups of...
crosslinking caused by UV exposure.
Recent research by J.D. Simon et al. suggests that melanin may serve a protective role other than photoprotection. Melanin is able to effectively ligate
Chemical ligation
Chemical ligation is a set of techniques used for creating long peptide or protein chains. It is the second step of a convergent approach. First, smaller peptides containing 30-50 amino acids are prepared by conventional chemical peptide synthesis. Then, they are completely deprotected...
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
In terms of structure and electronics, melanins are "rigid-backbone" conductive polymers composed of polyacetylenePolyacetylene
Polyacetylene is an organic polymer with the repeat unit n. The high electrical conductivity discovered for these polymers beginning in the 1960's accelerated interest in the use of organic compounds in microelectronics...
, polypyrrole
Polypyrrole
Polypyrrole is a chemical compound formed from a number of connected pyrrole ring structures. For example a tetrapyrrole is a compound with four pyrrole rings connected. Methine-bridged cyclic tetrapyrroles are called porphyrins. Polypyrroles are conducting polymers of the rigid-rod polymer host...
, and polyaniline
Polyaniline
Polyaniline is a conducting polymer of the semi-flexible rod polymer family. Although the compound itself was discovered over 150 years ago, only since the early 1980s has polyaniline captured the intense attention of the scientific community. This is due to the rediscovery of its high electrical...
"Blacks" and their mixed copolymers. The simplest melanin is polyacetylene, and some fungal melanins are pure polyacetylene.
In 1963, D.E Weiss and coworkers reported high electrical conductivity in a melanin, iodine-doped and oxidized polypyrrole
Polypyrrole
Polypyrrole is a chemical compound formed from a number of connected pyrrole ring structures. For example a tetrapyrrole is a compound with four pyrrole rings connected. Methine-bridged cyclic tetrapyrroles are called porphyrins. Polypyrroles are conducting polymers of the rigid-rod polymer host...
"Black". They achieved the quite high conductivity of 1 Ohm/cm. A decade later, John McGinness
John McGinness
John Edward McGinness , is an American physicist and physician. McGinness worked as a in the field of Organic electronics and Nanotechnology.-Education:McGinness studied physics at the University of Houston and after his B.S...
, and coworkers reported a high conductivity "ON" state in a voltage-controlled solid-state threshold switch made with DOPA melanin. Further, this material emitted a flash of light—electroluminescence
Electroluminescence
Electroluminescence is an optical phenomenon and electrical phenomenon in which a material emits light in response to the passage of an electric current or to a strong electric field...
—when it switched. Melanin also shows negative resistance
Negative resistance
Negative resistance is a property of some electric circuits where an increase in the current entering a port results in a decreased voltage across the same port. This is in contrast to a simple ohmic resistor, which exhibits an increase in voltage under the same conditions. Negative resistors are...
, a classic property of electronically-active conductive polymers. Likewise, melanin is the best sound-absorbing material known, because of its strong electron-phonon
Phonon
In physics, a phonon is a collective excitation in a periodic, elastic arrangement of atoms or molecules in condensed matter, such as solids and some liquids...
coupling. This might explain part of the reason behind melanin's presence in the inner ear
Inner ear
The inner ear is the innermost part of the vertebrate ear. In mammals, it consists of the bony labyrinth, a hollow cavity in the temporal bone of the skull with a system of passages comprising two main functional parts:...
.
Nobel Prize
The Nobel Prizes are annual international awards bestowed by Scandinavian committees in recognition of cultural and scientific advances. The will of the Swedish chemist Alfred Nobel, the inventor of dynamite, established the prizes in 1895...
in Chemistry was awarded to three scientists for their subsequent 1977 (re)discovery and development of such conductive organic polymers. In an essential reprise of the work by Weiss et al., these polymers were oxidized, iodine-doped "polyacetylene
Polyacetylene
Polyacetylene is an organic polymer with the repeat unit n. The high electrical conductivity discovered for these polymers beginning in the 1960's accelerated interest in the use of organic compounds in microelectronics...
black" melanins. There is no evidence that the Nobel committee was aware of the almost identical prior report by Weiss et al. of passive high conductivity in iodinated polypyrrole black or of switching and high electrical conductivity in DOPA melanin and related organic semiconductor
Organic semiconductor
An organic semiconductor is an organic material with semiconductor properties. Single molecules, short chain and organic polymers can be semiconductive. Semiconducting small molecules include the polycyclic aromatic compounds pentacene, anthracene, and rubrene...
s. The melanin organic electronic device is now in the Smithsonian Institution
Smithsonian Institution
The Smithsonian Institution is an educational and research institute and associated museum complex, administered and funded by the government of the United States and by funds from its endowment, contributions, and profits from its retail operations, concessions, licensing activities, and magazines...
's National Museum of American History
National Museum of American History
The National Museum of American History: Kenneth E. Behring Center collects, preserves and displays the heritage of the United States in the areas of social, political, cultural, scientific and military history. Among the items on display are the original Star-Spangled Banner and Archie Bunker's...
's "Smithsonian Chips", collection of historic solid-state electronic devices.
Although synthetic melanin (commonly referred to as BSM, or "black synthetic matter") is made up of 3-6 oligomeric units linked together — the so-called "protomolecule" — there is no evidence that naturally occurring biopolymer (BCM, for "black cell matter") mimics this structure. However, since there is no reason to believe that natural melanin does not belong to the category of the polyarenes and polycationic polyenes, like pyrrol black and acetylene black, it is necessary to review all the chemical and biological analytic data gathered to date in the study of natural melanins (eumelanins, pheomelanins, allomelanins)."
Evidence exists in support of a highly cross-linked heteropolymer
Heteropolymer
A heteropolymer or copolymer is a polymer derived from two monomeric species, as opposed to a homopolymer where only one monomer is used...
bound covalently
Covalent bond
A covalent bond is a form of chemical bonding that is characterized by the sharing of pairs of electrons between atoms. The stable balance of attractive and repulsive forces between atoms when they share electrons is known as covalent bonding....
to matrix scaffolding melanoproteins. It has been proposed that the ability of melanin to act as an antioxidant
Antioxidant
An antioxidant is a molecule capable of inhibiting the oxidation of other molecules. Oxidation is a chemical reaction that transfers electrons or hydrogen from a substance to an oxidizing agent. Oxidation reactions can produce free radicals. In turn, these radicals can start chain reactions. When...
is directly proportional to its degree of polymerization or molecular weight. Suboptimal conditions for the effective polymerization of melanin monomer
Monomer
A monomer is an atom or a small molecule that may bind chemically to other monomers to form a polymer; the term "monomeric protein" may also be used to describe one of the proteins making up a multiprotein complex...
s may lead to formation of lower-molecular-weight, pro-oxidant melanin that has been implicated in the causation and progression of macular degeneration
Macular degeneration
Age-related macular degeneration is a medical condition which usually affects older adults and results in a loss of vision in the center of the visual field because of damage to the retina. It occurs in “dry” and “wet” forms. It is a major cause of blindness and visual impairment in older adults...
and melanoma
Melanoma
Melanoma is a malignant tumor of melanocytes. Melanocytes are cells that produce the dark pigment, melanin, which is responsible for the color of skin. They predominantly occur in skin, but are also found in other parts of the body, including the bowel and the eye...
. Signaling pathway
Signal transduction
Signal transduction occurs when an extracellular signaling molecule activates a cell surface receptor. In turn, this receptor alters intracellular molecules creating a response...
s that upregulate melanization in the retinal pigment epithelium (RPE) also may be implicated in the downregulation of rod
Rod cell
Rod cells, or rods, are photoreceptor cells in the retina of the eye that can function in less intense light than can the other type of visual photoreceptor, cone cells. Named for their cylindrical shape, rods are concentrated at the outer edges of the retina and are used in peripheral vision. On...
outer segment phagocytosis by the RPE. This phenomenon has been attributed in part to fovea
Fovea
The fovea centralis, also generally known as the fovea , is a part of the eye, located in the center of the macula region of the retina....
l sparing in macular degeneration
Macular degeneration
Age-related macular degeneration is a medical condition which usually affects older adults and results in a loss of vision in the center of the visual field because of damage to the retina. It occurs in “dry” and “wet” forms. It is a major cause of blindness and visual impairment in older adults...
.
Bias in human societies
The act of placing skin pigmentation within a rubric of racial classification and linked to social status or other human attributes is known as racialism
Racialism
Racialism is an emphasis on race or racial considerations. Currently, racialism entails a belief in the existence and significance of racial categories, but not necessarily that any absolute hierarchy between the races has been demonstrated by a rigorous and comprehensive scientific process...
. Many people and societies overlay racialism with racist
Racism
Racism is the belief that inherent different traits in human racial groups justify discrimination. In the modern English language, the term "racism" is used predominantly as a pejorative epithet. It is applied especially to the practice or advocacy of racial discrimination of a pernicious nature...
perceptions and systems that arbitrarily assign to groups of people sharing a genetically transmitted pigmentation a status of inherent superiority or inferiority, privilege, or disadvantage based on skin color.
Apartheid-era South Africa
South Africa
The Republic of South Africa is a country in southern Africa. Located at the southern tip of Africa, it is divided into nine provinces, with of coastline on the Atlantic and Indian oceans...
is an example of a white supremacist
White supremacy
White supremacy is the belief, and promotion of the belief, that white people are superior to people of other racial backgrounds. The term is sometimes used specifically to describe a political ideology that advocates the social and political dominance by whites.White supremacy, as with racial...
society based on a system of stratification of power and privilege by skin color, as well as racial admixture. Similar examples can be found in Brazil
Brazil
Brazil , officially the Federative Republic of Brazil , is the largest country in South America. It is the world's fifth largest country, both by geographical area and by population with over 192 million people...
's highly socially color-stratified society; and, in the U.S., segregation
Racial segregation
Racial segregation is the separation of humans into racial groups in daily life. It may apply to activities such as eating in a restaurant, drinking from a water fountain, using a public toilet, attending school, going to the movies, or in the rental or purchase of a home...
, institutional racism
Institutional racism
Institutional racism describes any kind of system of inequality based on race. It can occur in institutions such as public government bodies, private business corporations , and universities . The term was coined by Black Power activist Stokely Carmichael in the late 1960s...
, and internal "color consciousness" on the part of members of some ethnicities.
See also
- Addison's diseaseAddison's diseaseAddison’s disease is a rare, chronic endocrine disorder in which the adrenal glands do not produce sufficient steroid hormones...
- Albino
- CaroteneCaroteneThe term carotene is used for several related unsaturated hydrocarbon substances having the formula C40Hx, which are synthesized by plants but cannot be made by animals. Carotene is an orange photosynthetic pigment important for photosynthesis. Carotenes are all coloured to the human eye...
- Griscelli syndromeGriscelli syndromeGriscelli syndrome is a rare autosomal recessive disorder characterized by albinism with immunodeficiency, that usually causes death by early childhood.-Types:...
A syndrome characterised by hypopigmentation. - Human skin colorHuman skin colorHuman skin color is primarily due to the presence of melanin in the skin. Skin color ranges from almost black to white with a pinkish tinge due to blood vessels underneath. Variation in natural skin color is mainly due to genetics, although the evolutionary causes are not completely certain...
- List of human hair color genes
- Mc1r
- Melanin theoryMelanin theoryMelanin theory is a pseudoscientific theory, founded in the distortion of the known physical properties of melanin, a natural polymer and organic semiconductor. In humans, melanin is the primary determinant of skin color. People whose ancestors lived for long periods in the regions of the globe...
, a pseudoscientific theory that ascribes supernatural abilities to melanin - MelanismMelanismMelanism is an undue development of dark-colored pigment in the skin or its appendages, and the opposite of albinism. It is also the medical term for black jaundice.The word is deduced from the , meaning black pigment....
- Melanogenesis, the increased production of melanin
- MelanomaMelanomaMelanoma is a malignant tumor of melanocytes. Melanocytes are cells that produce the dark pigment, melanin, which is responsible for the color of skin. They predominantly occur in skin, but are also found in other parts of the body, including the bowel and the eye...
- Melanotropin receptorMelanotropin receptorMelanotropin receptor is a protein found in skin and eye cells that make melanin . People with certain changes in the gene for the melanotropin receptor have a higher risk of developing melanoma...
- Organic semiconductorOrganic semiconductorAn organic semiconductor is an organic material with semiconductor properties. Single molecules, short chain and organic polymers can be semiconductive. Semiconducting small molecules include the polycyclic aromatic compounds pentacene, anthracene, and rubrene...
- Parkinson's diseaseParkinson's diseaseParkinson's disease is a degenerative disorder of the central nervous system...
- Risks and benefits of sun exposureRisks and benefits of sun exposureThe ultraviolet radiation in sunlight, though a principal source of vitamin D3 compared to diet, is mutagenic. Supplementing diet with vitamin D3 supplies vitamin D without this mutagenic effect, but bypasses natural mechanisms that would prevent overdoses of vitamin D generated internally from...
- SLC24A5SLC24A5Sodium/potassium/calcium exchanger 5 also known as solute carrier family 24 member 5 is a protein that in humans is encoded by the SLC24A5 gene that has a major influence on natural skin colour variation. The NCKX5 protein is a member of the potassium-dependent sodium/calcium exchanger family...
- Vitamin DVitamin DVitamin D is a group of fat-soluble secosteroids. In humans, vitamin D is unique both because it functions as a prohormone and because the body can synthesize it when sun exposure is adequate ....