Melanin is a naturally produced polymer found in a multitude of locations in the body, from the eye and ear, to the brain and skin. Each different location contains a different variety of melanin, such as neuromelanin in the brain, and eumelanin and pheomelanin in the skin. The functions of most of the melanins found in biology are not fully understood, except for melanin found in the skin, known as eumelanin or pheomelanin. Although the structures and the exact formation pathways of both skin melanins are not very well understood, mechanisms have been suggested (Figure 1). The chemical structure of the different forms of melanin in the skin has proven difficult to analyze due to the properties of the molecule. They are found to be insoluble, amorphous, and cannot be studied as a solution or in crystal form. To overcome these frustrating properties, a partial degradation process has been used to study the separate components of each melanin structure.
It is known that both melanins are synthesized at the bottom of the epidermis (top layer of the skin), in a region termed the basal layer. Special cells located in the basal layer, termed melanocytes, produce melanin containing packets, called melanosomes. This process is termed melanogenesis, and is initiated once the nuclei of skin cells begin to become damaged from ultraviolet radiation (UVR), emitted by either the sun, or an artificial source (such as a sun bed). The melanosomes are then spread to separate keratinocytes (skin cells) throughout the epidermis, carried by tentacle-like projections, termed dendrites. Once the melanosomes reach the end of the projections they are squeezed out, into the keratinocytes. The melanin containing packets spread out above the nucleus, where they stay, protecting the DNA inside the organelle from harmful UVR. The skin cells eventually rise to the top of the epidermis where they die and are desquamated (shed away).
Where reference is made to melanin in the text, eumelanin is implied. It is known that the melanin in the skin acts as a pigment, but the importance of melanin in most of the other organs is not well understood.
Melanin functioning as a pigment
In the skin, melanin functions as an absorptive pigment. A pigment is a substance that, as a result of selective colour (wavelength) absorption, determines the colours of many plants and animals. In humans, the two types of melanin present in the skin (eumelanin and pheomelanin) are responsible for different skin tone (which is induced by ultraviolet radiation), and the constituent of freckles.
Eumelanin is a black or brown pigment, and is mainly concerned with the protection of the skin by absorbing incoming UV radiation. This protective ability warrants melanin to be termed a photoprotectant (a substance capable of providing protection against radiation from the sun). Pheomelanin is a reddish pigment, a very weak absorptive of UV radiation, further it also acts as a photosensitizer (makes your skin sensitive to light), where it increases sun sensitivity and skin ageing.
Skin colour is determined by:
- The ratio of eumelanin to pheomelanin, where the more eumelanin present, the darker tone of an individual;
- The absolute amount and concentration of melanin in the skin; and
- The size of the packets that melanin travels in (melanosomes), the number of melanosomes, and how well spread the melanosomes are.
Melanin is produced in specialized skin cells located at the ‘bottom’ of the epidermis (top layer of skin) termed melanocytes. These melanocytes start producing melanin once damage occurs to the nuclei of cells in the skin, caused by ultraviolet radiation. This radiation can be either artificially (sunbeds) or naturally (sun) produced, and results in the biological release of alpha-melanocyte stimulating hormone (α-MSH). α-MSH binds itself to melanocyte cells, inducing the production of melanin within melanosomes. This overall process is termed melanogenesis. Once produced, melanin is transported to the upper levels of the skin through the outward growth of keratinocytes (skin cells). It has been found that the amount of melanocytes generally doesn’t vary between people, but the number of melanosomes, and subsequently melanin, can vary dramatically.
The production pathway of both eumelanin and pheomelanin is becoming better understood, it is known that the base amino acid is tyrosine, and tyrosinase is an important enzyme in the process of melanogenesis. Tyrosinase both initiates the synthesis of the two melanins, and is involved in steps further down the process line.
Melanin is able to protect the skin from UVR by several methods; it is able to scatter incoming UVR, absorb it, and can also absorb compounds produced by photochemical action which would be toxic or carcinogenic.
The amount of UV radiation that is absorbed or scattered is determined upon by a number of factors. The size, shape, and distribution of melanosomes, as well as the wavelength of the incident ray. The absorption spectrum for melanin at different wavelength is shown in Figure 1.
Various ethnic origins
According to Charles Darwin (1859), evolution is driven by natural selection, where those best suited to an environment are most likely to survive and reproduce. In this manner man evolved from dark to fair skinned. The first humans are thought to have originated in Africa, where those who had developed darker skin demonstrated a better chance of survival, as the excessive amounts of melanin prevented folate from being destroyed in the blood. As man began to migrate north, to less sun drenched areas, the dark tone of the skin became an undesirable trait, as with the lack of intense radiation came a deficiency in vitamin D. Vitamin D is an essential nutrient where the synthesis is initiated in the skin and whose production is stimulated by UV radiation. Many factors influence vitamin D synthesis, but if the UV radiation isn’t intense enough, the ionizing radiation will not be able to pass through epidermis, and hence vitamin D synthesis will be deficient. Historically therefore, lighter skinned humans were better able to adapt to their environment and more likely to survive. Reproduction gave rise to fairer skinned humans and evolved to the various races we have today.
It is generally accepted that eumelanins are macromolecules of DHI (5,6-dihydroxylindole) , its carboxylated form, DHICA (5,6-dihydroxylindole-2-carboxylic acid), and their various redox states (Figure 4). These macromolecules are regarded as the molecules primary structure. It has been found that coupling between these molecules is most likely to occur at positions 3, 4, and 7, which inevitably leads to chemical disorder. This chemical disorder and range of bonding positions leads to a number of different polymeric structures that are all termed eumelanin.
There is uncertainty over the secondary structure (arrangement of alpha helices, beta sheets, and coils) of eumelanin, which can be expected when the multitude of bonding arrangements that can be produced by the various monomers is considered.There are two predominant models that exist – the large heteropolymer model, and the recently suggested stacked oligomer model - which both explain the chemical properties of eumelanin in different ways.
The heteropolymer model suggests that the coupling of monomers occurs via random bonding, while this theory ignores the mechanisms of how the monomers become coupled. Until recently, the heteropolymer model was thought to be the only way to describe the optical and absorption properties of eumelanin. In the mid 1990’s, X-ray scattering and scanning tunneling were used to suggest a vastly different model. This model assumes eumelanin is composed of oligomeric (a molecule made up of small monomers) plates (Figure 5). Since the first suggestion of the stacked model, several advances and tests have pointed to the correctness of Zajac et al’s (1994) findings.
Pheomelanin, like eumelanin, has base macromolecules of DHI, DHICA and their redox states (Figure 6). It differs from eumelanin in that its structure, either oligomer stacks or the heteropolymer model, also incorporates the cysteine amino acid in to it.
The photoprotective properties of melanin are directly related to the absorption and scattering of incoming radiation.
As the percentage of incident radiation that undergoes scattering increases, the likelihood of the radiation coming into contact with DNA is reduced. The amount of radiation that passes through to the DNA is dependent on the wavelength of the incident ray, and the size of the particles that it is striking. For a wavelength of 300nm, forward scattering dominates when the particle size is above 30nm. Therefore, smaller particles result in a greater percentage of backward scattering, which is biologically preferred. Chedekel et al describe that the radiation can be reflected and refracted by melanin until it is reemitted out of the skin, or it is absorbed by melanin or other cutaneous absorbtive substances (chromophores).
The sizes of human melanosomes are thought to range from about 228nm to 684nm. It is therefore desired, on a scattering basis, to have melanosomes closer to 230nm rather than 690nm, while absorption is favoured by a large surface area, leading to a need for large melanosomes.
The amount of energy absorbed also depends on the wavelength of the incident ray (see Figure 8 for absorption spectrum), melanin is best suited to absorb radiation in the range of 340nm, which is in the UVA/B region.
Once the energy is absorbed by melanin, electrons are raised to excited states and in turn, pass the energy on to the cell in which it is situated . Simon reported that most (99%) of the energy absorbed is dissipated ‘non-radiatively’ within a nanosecond of excitation. The cell is then assumed to use this energy to regulate its conditions and drive chemical reactions, a role similar to that of chlorophyll in photosynthesis. It is widely supported that with increased melanin density in the skin, patients are less likely to encounter UV exposure related diseases.
- Meredith, P and Sarna, T (2006). "The physical and chemical properties of eumelanin", Pigment Cell Research. Vol 19, pp572-594.
- Jablonski, N and Chaplin, G (2000). "The Evolution of human Skin Coloration", Journal of Human Evolution. Vol 39, pp57-106.
- Simon, J D (2000). "Spectroscopic and dynamic studies of the epidermal chromophores trans-urocanic acid and eumelanin", Acc. Chem. Res. Vol 33 (5) pp307-313.
- Chedekel, Zeise and Fitzpatrick (1994). Melanin: Its role in Human Photoprotection. Valdenmar Publishing Company.
- Zajac, G W et al (1994). "The fundamental unit of synthetic melanin: verification by tunnelling microscopy of X-ray scattering results" Biochem. Biophys. Acta. Vol 1199 (3), pp271-278.
- Miyamoto, K and Baba, K (1987). "Stereological Method for Unfolding Size-Shape Distribution of Spheroidal Organelles from Electron Micrographs" Journal of Electron Microscopy. Vol 36 (3), pp90-97.
- Darwin, C (1859). On the Origin of Species. John Murray, Britain.