Melanin Explained
Brown skin, black skin, tanned skin. Melanin.
Black hair, blonde hair, red head. Melanin.
We have all heard about melanin, but what is it actually? Melanin is a pigment, a group of chemicals found throughout nature not just people. There are different types of melanin some of which will be explored later but the property that makes melanin so special, is it’s ability to absorb a good range of radiation (electromagnetic wavelengths) unlike some other natural pigments. The more you have the better your skin is at absorbing radiation.
Before we start I would like to address a popular misconception about darker skin,
“Black people don’t need to use sunscreen”
Whilst it’s true that dark skin is better at protecting itself from UV rays than fairer skin, it does not mean you are being fully protected. Sunburn is the body’s response to DNA being damaged, darker skinned people may not burn, but after a lot of UV exposure you could have sunburn without even noticing it. The sun will still cause damage to your DNA and cause you oxidative stress!
Darker skinned individuals have a lower chance of getting melanoma (skin cancer) HOWEVER they’re less likely to survive skin cancer than their fair skinned counterparts. This is because it is so much easier to miss the early signs of skin cancer in darker skin. When it is discovered, it has a higher chance of being discovered in an advanced stage of cancer where the chance of survival is low. Riddle me this, do you know what melanoma looks like?
Melanin’s ability to absorb radiation is what makes me black
Melanins ability to absorb a large range of radiation is the reason why it’s a dark pigment. Thought experiment. Everything you see is light reflecting off the surface of something. Turn off the light in a room and you see nothing. If an object manages to absorb all of the visible light, you see black. For example they have developed a paint called Vantablack 2.0 (google it) which absorbs over 99% of visible light and when you see the images it quite literally doesn’t even look real at all.
Melanins ability to absorb radiation is what makes the pigment dark, and you need a lot of it to be darker skinned. The concentration (amount) of melanin pigment in the skin of POC is higher hence we have darker skin than less melanated people.
What’s the point of melanin?
Remember the electromagnetic spectrum that you learned about in secondary school, radio waves, microwaves, visible light, ultra violet (UV) and X-rays. In our everyday lives we are constantly exposed to different forms of radiation, be it our phones, or UV rays from the sun. Or when you break a bone and you undergo a X-ray. Some portions of the spectrum are “harmless”, by this I mean you can have lifetime long exposures to them and not face any direct consequences of exposure.
Some forms of radiation are dangerous, depending on the energy of the wave. For example gamma waves carry the most energy, in comparison to a wave like UV. Acute exposure to gamma radiation for a couple minutes would have you dead in around 2 weeks, but there is a possibility to go a whole lifetime with exposure to UV and have no ill effects.
The ability for melanin to absorb large ranges of radiation is what makes it special. Melanin absorbs a good portion of electromagnetic waves, so that it doesn’t penetrate the skin and cause damage.
Damage? It’s just sunburn
If UV is not absorbed by melanin, it can wreak havoc to the molecules in your body. People underestimate the process that occurs when you get sunburned. People shrug it off, everyone thinks of it as a literal burn, inconvenient, painful but you can get over it. However this is far from the truth sunburn is scary.
Sunburn is the body’s reaction to direct DNA damage in the body. It’s not just a burn.
DNA can be found in multiple different states within the body, some DNA is tightly wound so its not activated whilst some is being replicated into RNA so proteins can be made. Control of DNA and its activation are a very complex but essential feature your body has to have in order to operate efficiently, it’s why you can get sweaty hands but not phlegmy (mucus/snotty) hands. It’s why your liver breaks down alcohol, but your lungs don’t, each part of your body has a different purpose in which specific sequences of DNA are needed for but others are not.
Nearly all cells contain all the DNA information that defines your body, but in order to become a specialised cell certain DNA is turned off and on so that a specific purpose can be reached, it’s what makes a liver cell different from a kidney cell. A liver cell will have the DNA active which allows for proteins to be made to break down molecules, however a kidney cell will have DNA active that will allow for proteins to be made that allow it to draw “useful” molecules like sodium ions and chloride ions out the blood stream. This is a simplified view but its essential to understand for the explanation of the damage caused.
This is the essence of the molecular biology central dogma, it’s the flow of information from DNA to the end product. I have included a diagram, for easy visualisation. The end point is the protein/enzyme which carries out a function, like any flowchart issues in early stages can be carried on till the end. Defence mechanisms exist but these exceed the scope of this piece.
DNA is what allows a cell to perform its function. DNA will often be translated in proteins which will each perform a job.
Another thought experiment. Imagine we have a section of DNA that codes for a protein called X. Protein X’s role is to regulate how often the cell replicates itself. UV can cause direct damage to the DNA in which protein X is made from, which would reflect in a mutation occurring in protein X.
There are three outcomes, protein X would either, cease to perform its function, perform its function even quicker or slower or have a negligable change. Let’s say this mutation causes it to work at a quicker rate, so it makes the cell replicate itself even quicker. Even though this is a simplistic view, ladies and gentlemen this is how cancer occurs. The cell would continue to replicate and eventually become a localised collection of cells that would then be defined as a tumour.
Thats all doom and gloom but again, remember melanins main characteristic, the thing that makes it special. Melanins helps to prevent this process from occurring by absorbing the radiation before it reaches the DNA. People with the ability to tan are an excellent example of this, exposure to UV causes their body to increase the concentration of melanin in their skin, giving them a darker look, a clever first line defensive mechanism. Paler people who don’t have a strong ability to create melanin in the sun will obtain sunburn much more easier, but darker skinned people have a much stronger first line of defence to radiation.
How is damage caused?
Thymine Dimers and Free Radicals
Just to reiterate UV rays are high energy waves, but what exactly does it do to your DNA? Adenine, Thymine, Cytosine and Guanine each of them in an exact sequence, which code for your existence. However if two thymines are adjacent in the sequence the UV can cause them to react to each other binding them together.
UV also interacts with the Oxygen present in your skin, causing them turn into a free radical particle. They are very unstable and will react with nearly anything, luckily though your skin cells are full of biological and organic molecules so they can “absorb” the hit. But a free radical in close proximity of something important such as DNA replicating machinery, or DNA itself can cause cell damage directly.
A Biochemists view of melanin
Melanin usage in other species
Melanin has a diverse set of functions in other organisms, other than simply protecting them from harmful UV rays. Fungi use melanin to capture and harvest energy from electromagnetic radiation in a process known as radiosynthesis. This is due to the electrical properties of the molecule. The immune systems of some insects and nematodes are based on melanin, whilst in the contrary some pathogens use melanin to evade immune responses from the host they are invading.
Melanin is not a protein, it is a molecule formed down a reaction pathway by enzymes which will be referred to later, the diagram above highlights some of the structures. What you need to know is the vast number of benzene rings, and bonds is what makes it good at absorbing the energy. Explaining the exact mechanism is beyond the scope of this blog but I have decided to include the chemical structure of some active ingredients in sunscreen. Have a look at the similarities between the molecules.
Melanin exists as three forms, eumelanin, pheomelanin and neuromelanin. Eumelanin further divided into two, a black and brown form. Pheomelanin is yellow-red pigment and the ratio of these two in skin, hair and eyes decide the colour which is achieved. Pheomelanin is the reason for the pinkish skin colour of various body parts such as your lips.
For example, black and brown hair is created when only black and brown forms of eumelanin are present, whilst in blonde hair a small amount of brown eumelanin has to be present with pheomelanin. Red hair occurs when there are equal amounts of both eumelanin and pheomelanin.
Melanin Production
Melanin is produced in a complex process called melanogenesis, and is produced by cells called melanocytes in their organelles called melanosomes. Apologies for the tongue twister, but it’s important to understand the distinction between the words so you don’t get confused later. Melanosomes are organelles, essentially see them in the same way you see the word organ. It’s very hard to survive without organs, in the same way that a cells organelles can define the purpose of the cell. Without the organelles, it’s just there taking up space doing nothing.
Melanasomes are also found in some of the cells that make up your eyes, as they would provide some of the pigments that would colour them. We will focus on the role of the melanosomes found in your skin (epidermis).
Activation
Proopiomelanocortin (αMSH) , a hormone, is released by keratinocytes as a result of UV exposure. This activates melanocortin 1 receptor (MC1R) in the membrane of melanocytes (the cell), which results in downstream signalling and expression of MITF which has a function of regulating the process of melanogenesis.
Synthesis
Melanosomes has 4 distinct stages of development which allow it to perform its function. Stage 1 pre-melanosomes are non-pigmented, stage 2 involves a protein called Pmel17, this protein is essential for the melanosomes filamentous striation structure of the cell. Key enzymes, tyrosinase and TRYP1, are delivered to the cell as well in order to begin making melanin. During stage 3 melanin pigment is deposited into the striations and finally a stage 4 melanosome is the fully melanised and mature version of itself ready to perform its function.
Transport
The final destination of a melanosome containing the pigment is the keratinocytes in the skin. Unfortunately this process is not well understood, but there are some theories into how this occurs. One is the exocytosis of melanosomes which is followed by the phagocytic uptake into the keratinocytes. This in simpler terms is the cell “spitting out” the melanosome and it being essentially swallowed by the receiver cell. Another method theorised is a tunnel like membrane structure where the melanosomes are transported through into the receiver. Who knows? But that’s the beauty of science, eventually someone will figure out the mechanism and this sentence will disappear as a whole.
Disease
DNA ultimately decides how this process occurs in your body and mutations to your DNA can cause certain steps, proteins or enzymes to be impaired and not work as they should. Having impaired function of melanocytes can cause vitiligo, which is characterised by white patches surrounded by normally pigmented skin. This is an autoimmune condition. The immune system destroys melanocytes in the body stopping them from creating melanosomes to be transported to the upper skin.
TYRP1
TYRP1 is one of the three enzymes responsible for the creation of melanin, there has been difficulty in obtaining the structure of TYRP1 and this has slowed down research being conducted on to the structure and function of this enzyme. It is one of the enzymes transported to the melanosome during its development.
What’s the point of characterising the structure of a protein?
Solving exactly how this enzyme works has a number of benefits, firstly it means we can make predictions on how newly discovered proteins/enzymes in the future would work, if they have a similar structure to this enzyme. Secondly comparisons can be made between a correctly functioning enzyme and an enzyme from a diseased individual, by looking at the DNA that codes them and how it makes a difference. Albinism is an example of a disease which occurs when there are mutations present in the DNA sequence that makes these.
Defining the structure also allows for potential therapeutic applications to be developed. Certain variations of this enzyme have a significant association with the risk of gaining melanoma. This means potentially in the future you could have your DNA sequenced and if you have a variant which is associated with a higher risk you can start to take active steps to prevent it occurring. There have been clinical trials which target the inhibition of melanogenesis using monoclonal antibodies, which can result in higher chance of effective therapeutic intervention.
The crystilisation of this enzyme has casted significant doubt on a assumption that was made about how the enzyme functions. This assumption was made about the metal ion present in it’s active site for over 3 decades!!! However the structure shows that there is zinc present in the active site, which gives more clues for how the enzyme functions but future research will try and solve how it works.
Conclusion
First and foremost wear sunscreen no matter what skin colour you are to protect yourself from the sun.
But I hope you have enjoyed this scientific blog, and have come away from this with some new knowledge. It took me a long time to write this, but I am happy to finally share this with all of you.
References
I have not included intext citations, however if you would like to know where I obtained a specific piece of information from, contact me.
Lai, X. et al. (2017) ‘Structure of Human Tyrosinase Related Protein 1 Reveals a Binuclear Zinc Active Site Important for Melanogenesis’, Angewandte Chemie — International Edition, 56(33), pp. 9812–9815. doi:10.1002/ANIE.201704616.
Meredith, P. and Sarna, T. (2006) ‘The physical and chemical properties of eumelanin’, Pigment Cell Research, 19(6), pp. 572–594. doi:10.1111/J.1600–0749.2006.00345.X.
Rastogi, R.P. et al. (2010) ‘Molecular mechanisms of ultraviolet radiation-induced DNA damage and repair’, Journal of Nucleic Acids, 2010. doi:10.4061/2010/592980.
Schlessinger, D.I., Anoruo, M. and Schlessinger, J. (2021) ‘Biochemistry, Melanin’, StatPearls [Preprint]. Available at: https://www.ncbi.nlm.nih.gov/books/NBK459156/.
Sinha, R.P. and Häder, D.P. (2002) ‘UV-induced DNA damage and repair: a review’, Photochemical & Photobiological Sciences, 1(4), pp. 225–236. doi:10.1039/B201230H.
Wasmeier, C. et al. (2008) ‘Melanosomes at a glance’, Journal of Cell Science, 121, pp. 3995–3999. doi:10.1242/jcs.040667.
Chemspider.com for the chemical structures of the suncreen active ingredients
Eu + pheo melanine obtained from https://www.researchgate.net/figure/Structure-of-eumelanin-and-pheomelanin-The-positions-with-COOH-in-eumelanin_fig2_331903150
