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To have an effect, a molecule must bind to a receptor and trigger a signal.  Studying a receptor’s structure can give us insights about the way this triggering process works.

Capsaicin is a fascinating molecule that puts the “pep” into peppers.  Curiously, the amount of capsaicin in a pepper is measured with a test devised in 1912 by Wilbur Scoville.  Dried peppers are dissolved in alcohol, this liquid extract is diluted in water, and trained people determine the pepper’s Scoville value by “tasting” the heat.

I wonder how these people are recruited.   I like hot sauce but I can’t imagine being a Scoville chili tester, largely because of the chili’s effects.

What do you feel when you eat chilis?

Heat?  Pain? Both?

What you feel results from a signal by the capsaicin receptor (TRPVI).  What can the structure of the capsaicin receptor tell us about its function?  Can we learn things from the capsaicin receptor that will help understand how other receptors work?  Like the wasabi receptor?

Let’s find out.

capsaicin

Capsaicin

 

 

 

 

 

 

 

 

 

 

 

 

 

Where does the capsaicin receptor hang out?

A good place to start is to figure out where the receptor is located in a cell.

We know some receptors are found in membranes, but others, like the estrogen receptor are located inside the cell.  Those kinds of receptors move into the nucleus and bind to DNA when they’re target molecule enters the scene.

Other kinds of receptors stick through the cell membrane.

We can answer this question using Molecule World, a molecular modeling program for the iPad®, to color the TrpVI receptor model (3J5P) by charge.  We’re only showing the core backbone of the protein below and hiding the amino acid side chains. That view lets us to see the secondary structure a bit more clearly.

capsaicin_charge

 

 

 

 

 

 

 

 

In the image above, you can see there are lots of helices on one side of the receptor and they’re all colored grey.  A grey color is commonly used to represent neutral or uncharged residues.  If we color by hydrophobicity, we’ll also learn these regions are hydrophobic.  That tells us this part of the receptor is stuck in the membrane.

But which end is outside the cell?  What do you think?  Is it the cup-shaped end, the flatter end, or is the structure turned sideways in the image above?

To answer this question, we need a little more help.

Capsaicin isn’t the only thing that sends signals through this receptor, changes in pH, heat (~42°C), molecules like lysophosphatidic acid (LPA), and certain spider toxins, can affect signaling as well.

What does it feel like when you’ve been bitten by a spider?

Luckily, Liao et. al. (1) solved the structure of the capsaicin receptor in the presence of a spider toxin (3J5Q).  This spider toxin is a useful tool for us because it’s a protein and can’t go through the cell membrane.  This means we can use it to figure out which side of the receptor is inside the cell and which side is out.

In this image, I selected the spider toxin proteins and colored them by molecule.

You can see all four molecules of spider toxin are bound on the flat side of the receptor.  Since the grey region is in the membrane, the cup-shaped portion must be located inside the cell.

spider_capsaicin

 

 

 

 

 

 

 

 

 

And that’s not all.

If we have both structures downloaded in Molecule World, we can compare the model of the TrpVI receptor alone to the model bound to spider toxin.

When we alternate between structures, it’s almost like you see the channel open up.

image

 

 

 

 

 

 

 

 

What goes through the channel?

Since the structure is colored by charge, we can make some guesses about the kinds of ions that pass through the open channel.

 

What did this have to do with the wasabi receptor?

Now that you’ve experimented with the capsaicin receptor, you can apply what you’ve learned to a new structure that was solved just recently (2).  Use the PDB ID 3J9P to download the wasabi receptor in Molecule World from the PDB database.

You should be able to tell where the receptor is located in the cell, make a guess about which side is inside and which is out, and guess the kinds of ions that pass through the channel.

Have fun!

 

References

1. Liao M, Cao E, Julius D, Cheng Y. Structure of the trpv1 ion channel determined by electron cryo-microscopy.  Nature (2013) 504 p.107

2.  Paulsen CE, Armache JP, Gao Y, Cheng Y, Julius D.  Structure of the TRPA1 ion channel suggests regulatory mechanisms.  Nature. 2015 Apr 8. doi: 10.1038/nature14367. [Epub ahead of print]

 

 

 

 

 

Comments

  1. […] Source: Some like it hot – receptors for capsaicin and wasabi [Discovering Biology in a Digital World] […]

  2. #2 Herman
    April 12, 2015

    I really like the use of the molecular model, as it really helps me to understand better.I do however think that the descriptions are not always easily understandable and i often had to read through a passage three or four times to get a better idea of what is meant.I could be the only one who felt this way but would like to know whether someone else maybe had the same problem.

  3. #3 Yeni Totjeka
    Port Elizabeth
    April 12, 2015

    Wow! This is fascinating!

  4. #4 Susan Blouw
    Windhoek
    April 12, 2015

    Are these receptors only located in the membranes on the tongue, of right through the body’s membranes?

  5. #5 Mariëtta Janse van Rensburg (15087132)
    Pretoria
    April 12, 2015

    This is remarkable. This receptor serves as a multi purpose mechanism in the cell, because it allows the passage of ions through the cell, it detects changes in pH and heat and the intensity of both these quantities.

  6. #6 Claudia Gevers (u15040862)
    April 12, 2015

    It is very interesting to be able to understand why some food burn more than others. An interesting question would be why people experience the heat differently, for example i can’t handle hot foods while my uncle is able to eat chillis as a midday snack.

  7. #7 Simon Walks
    Lusaka
    April 12, 2015

    I read on Health Votes once that wasabi can help to fight bacteria, to reduce inflammations, and can suppress blood clots and cancer cells within the body.

  8. #8 Mariëtta Janse van Rensburg (15087132)
    Pretoria
    April 12, 2015

    Wasabi receptors will probably have the same function as the capsaicin receptor except for the fact that the signals will be influenced by wasabi rather that capsaicin.

  9. #9 Nicole Konstantinopoulos
    South Africa
    April 12, 2015

    To understand how these receptors work is very fascinating, however, why do people experience heat differently? What about the receptors in each individual determines if it’s a mild zing or an extra hot burn?
    14392357

  10. #10 Alessandra
    South Africa
    April 12, 2015

    This is so fascinating! The molecular model also helps me understand the processes better. Are these receptors located throughout the body?
    15014518

  11. #11 Dominique u15051197
    Pretoria
    April 12, 2015

    This is fascinating! I agree that wasabi receptors will have the same function as the capsaicin. It would be interesting to look into what ions are passing through these receptors and how that relates to the burn people experience.

  12. #12 Dominique u15051197
    Pretoria
    April 12, 2015

    It would be great to look deeper into the transfer of ions here and get a sense of how that relates the burning sensation.

  13. #13 Lisa u15179738
    Pretoria
    April 13, 2015

    Another interesting fact about this topic is that when foods containing capsaicinoids are eaten, the capsaicinoids irritate the tigeminal cells, these are the cells that release a chemical into the blood to tell the brain that you have eaten something hot. The brain responds by flushing the body with water. This is why after consuming a particularly hot Chile some people suddenly break into a sweat, their nose runs and they get teary eyed.

  14. #14 Lerato Dibokwane-u15054591
    Pretoria
    April 13, 2015

    The awesome discoveries like the molecular model really provides a clear understanding to the molecular makeup of our bodies and paves a way for other fascinating discoveries

  15. #15 KP Sedibane
    Pretoria
    April 13, 2015

    Wow this is very interesting, at least i know why some food burn. People feel the burning on different places, for example just down the chest, does this mean that they are situated in the digestive system or on specific places?

  16. #16 Xongile Mbiza, 15062237
    South Africa,Pretoria
    April 13, 2015

    This is news to me, i can now why we are able to detect the chilliness of food. The capsaicin does its work very well thus the complex structure it has. But the information does not really explain how it really works and how it relates to wasabi.

  17. #17 Brian Ndlovu 15162894
    South Africa, Pretoria
    April 13, 2015

    @Herman, I have the same problem too. I guess we have to grasp science terminology used often in these blogs and be a regular and active science blog participant, i guess with time we will be accustomed to this blogging language that science bloggers use. Receptors i wonder, as it’s not clearly outline in the blog vary from person to person, if so why is that the case? for instance somebody eat meal with chill without any problem to it chilly taste. Does receptors get use to a certain taste for instance or what cause this?

  18. #18 Rebecca Marshall (15086331)
    Pretoria
    April 13, 2015

    It is interesting to understand how and where the capsaicin binds to the receptors. What is also quite intriguing is that casein, a protein molecule found in milk, breaks the bonds formed between the receptors and capsaicin. Water however has no effect as capsaicin is an insoluble molecule. Thus it is more effective to drink milk instead of water to reduce the heat after a spicy meal.

  19. #19 Genevieve Gand - 15020054
    Pretoria
    April 14, 2015

    Its interesting to find out the effect of receptors as a result on combining capsaicin. But as said previously, what actual effect causes the initial burning sensation which one may eventually get used to? Further research would be credible to establish how the palette familiarizes itself to the burning sensations with certain tastes such as wasabi. The fact that the affect of the binding seems to differ to a variety of individuals which is also interesting.

  20. #20 Alone Joubert - 15102522
    Pretoria
    April 14, 2015

    The article discussed a very interesting topic. The fact that there are specific receptors triggered only by wasabi and others only by capsaicin is something to think about, does this mean that there is an individual receptor for each type of food? I looked into that on various internet sites, but very little information is given. It would be very interesting to look into this and run a few tests to help us understand the receptors located in our bodies so much better.

  21. #21 Alone Joubert - 15102522
    Pretoria
    April 14, 2015

    The fact that there are specific receptors triggered only by wasabi and others only by capsaicin is something to think about, does this mean that there is an individual receptor for each type of food? I looked into that on various internet sites, but very little information is given. It would be very interesting to look into this and run a few tests to help us understand the receptors located in our bodies so much better.

  22. #22 DB Mokone (14336830)
    Pretoria
    April 14, 2015

    It is interesting to see how these toxins and receptors are arranged , and how their arrangement works together with the wonderful nervous system of a living being in order for interpretations to lead to sensations( this all being the body’s way of protecting itself in alerting you) amazing work done to bring such things to visualization
    14336830

  23. #23 MH Phasha
    Pretoria
    April 15, 2015

    An interesting fact about why you would drink milk to cancel out the burning sensation after consuming spicy food. The reason is milk contains a special protein called casein which surrounds and binds with capsaicin molecules and washes them away. It’s all at the molecular level.
    28276362

  24. #24 Wann-Chyi Wu 15019277
    Pretoria
    April 15, 2015

    It is interesting to see that there are so many receptors and it responds differently to each kind of substance but what causes the “burn” that you feel and why do people differently to the hotness of the food?

  25. #25 Theo Hohls
    South Africa
    April 15, 2015

    Its interesting to think that just by deterimining the amount of ions that pass through a single receptor it may determine how a person experiences heat. Could further research into this actually lead to the development of a “hot scale” that a person can relate to based on what they know about their own receptors?? interesting to think how this receptor is able to detect a the ions passing throw and how it associates these ions with heat! Very interesting comment made by Lisa 13 about how the body flushes itself with water when a detection of capsaicin. u15016677

  26. #26 musawenkosi madonsela 14122309
    pretoria
    April 15, 2015

    what i wanna know is why people do not experience heat the same is that their receptors are not the same or it goes by that you are used to it?

  27. #27 Elden
    April 15, 2015

    I read on Health Votes once that wasabi can help to fight bacteria, to reduce inflammations, and can suppress blood clots and cancer cells within the body.
    (u15093702)

  28. #28 Nompumelelo Sibanyoni (15034552)
    Pretoria
    April 15, 2015

    This is really amazing. So this means that without these receptors the temperature wouldn’t be regulated after eating spicy food. So do the calcium ions pass through?

    • #29 Sandra Porter
      April 16, 2015

      Yes.

  29. #30 Jason Louw (u15156738)
    South Africa
    April 15, 2015

    It is interesting to note that there are multiple types of Capsaicin including: Capsaicin, Dihydrocapsaicin, Nordihydrocapsaicin, etc. Each Capsaicin type has a different ‘average’ unit on the Scoville Scale with Capsaicin being the highest at 16,000,000 heat units compared to the 1,200 heat units of a average bottle of Tabasco.

    Thank you for the informative article.

  30. #31 Christiaan de Jongh
    UP
    April 15, 2015

    This was really interesting! The molecular models helped me to get a better idea of what was being said, I also realized that there is still a lot of research that needs to be done on this topic? I will certainly have different thoughts when I eat spicy food from now on!

    15012868

  31. #32 Benita Labuschagne
    UP
    April 15, 2015

    wow! this was really an eye opener for me! I will also eat my spicy food with different thoughts from now on!

  32. #33 Billy Stander
    UP
    April 15, 2015

    I have never thought of taste in the way that I see it now after reading this article

  33. #34 M Hertzog
    April 16, 2015

    It is amazing to think that there are so many receptors on your tongue just to sense a burning sensation. It is also amazing how your tongue doesn’t really get hurt by the ”burn” and that it is just your brain telling you that it hurts when is actually doesnt.

  34. #35 M Hertzog
    April 16, 2015

    (15044654)

  35. #36 Stellar
    Pretoria
    April 16, 2015

    I am studying food science and technology and I find this blog page very interesting. It’s wonderful to see the science behind things we eat in our everyday lives!

    (14020123)

  36. #37 Stellar
    Pretoria
    April 16, 2015

    This is very surprising information, I had no idea that penguins had limited taste. But I suppose if they don’t chew their food and just swallow it they wouldnt taste much anyway! It is also interesting to learn that cats cannot taste sweet. Where does this leave dogs? Can they taste the 5 basic tastes?

    14020123

  37. #38 Stellar
    April 16, 2015

    Apologies, the above comment of mine applied to a different blog.

    I am studying food science and technology and I find this blog very interesting. It’s wonderful to see the science behind things we eat in our everyday lives.
    14020123
    14020123

  38. #39 Schoombie JD
    April 16, 2015

    Okay so now that we know about the burning sensation, what is the reason for dairy products such as milk giving one a soothing sensation to ease the burn of a chilli ,for example, when one drinks it ( the milk)?
    (15010989)

  39. #40 Sofia Vasconcelos (14437229)
    Pretoria
    April 16, 2015

    There is nothing more fascinating than the human body and how it all comes together so perfectly to function.
    I will definitely keep this in mind while enjoying my next spicy dish!

    This did make me wonder however if this means that we have different receptors for all kinds of foods, or if a single receptor is able to pic up different ‘signals’?

  40. #41 Stellar
    Pretoria
    April 16, 2015

    I am studying food science and technology and I find this blog very interesting. It’s wonderful to see the science behind things we eat in our everyday lives.
    14020123

  41. #42 Charne Coetzer
    Pretoria
    April 16, 2015

    I found this blog very useful as I really enjoy eating spicy food while other people cannot handle it at all. The molecular models really helped me to understand the article better.
    14010926

  42. #43 Rebekah Janse van Rensburg
    University of Pretoria
    April 16, 2015

    This is an interesting article as it helps me understand the science behind the spice, especially with the molecular models. Surely people react to the spicy heat differently, why is this so? Also, is it able to adapt to such spicy foods? And could you damage your cells by consuming too much spicy food?
    u15249396

  43. #44 Z Manzini (u15037097)
    UP
    April 16, 2015

    This was really interesting to read and it was very informative especially because we are learning about molecular structures in chemistry at the moment. I now have an example on the topic.

  44. #45 Nompumelelo Sibanyoni (15034552)
    Pretoria
    April 16, 2015

    This is interesting. What I would love to know is that what would happen to all the processes being done by these receptors if their structure decides to change?

  45. #46 Eileen Engelbrecht (15327192)
    Pretoria
    April 16, 2015

    What is really interesting to me is the fact that it’s the same receptor that receives signals not only from the molecules in peppers, but also from changes in pH, heat, other molecules like lysophosphatidic acid (LPA), and spider toxins. Does this mean that being bitten by a spider feels that same way as a really hot pepper tastes like??
    Another really cool thing is this model that they used. It is truly incredible to see the molecule in such a way. It really opened my eyes to the diversity of the molecular world.

  46. #47 Myles Illidge, 14094283.
    Pretoria
    April 16, 2015

    I find it very useful and interesting to know the make up of the everyday things we eat. Do the hydrophobic regions of the capcaisin molecule cause water to not remove the heat from chili?

  47. #48 Myles Illidge, 14094283.
    Pretoria
    April 16, 2015

    I find it very useful and interesting to learn the make up of the common, everyday things we eat.

    Is it because of the hydrophobic regions in the capsaicin molecule that water is not very effective in relieving the burning sensation?

  48. #49 rolindela pernell nelukalo
    pretoria
    April 17, 2015

    amazing are thi receptor connected to the whole body?

  49. #50 Suhail Solim (u15282270)
    Sandton
    April 17, 2015

    Its very interesting to know how our body reacts to chili. However some people are more resistant to chili than others. Can this also be explained by our membrane structure or is it only a question of taste?

  50. #51 Myles Illidge, 14094283.
    April 17, 2015

    Another use of Capsaicin is to repel insects. It manages to damage the membranes in cells, and cause problems in the nervous system.

    It amazes me to see how many uses there are for this molecule.

  51. #52 Dillan Baytopp (u14108608)
    Pretoria
    April 17, 2015

    Amazing how these receptors are able to create this burning sensation without actually burning at all and very interesting use for spider toxin.

  52. #53 ZG Manzini u15037097
    UP
    April 17, 2015

    Is true that Capsaicin decreases the intensity of pain by first stimulating it?

  53. #54 Monique
    Pretoria
    April 17, 2015

    i find it rather interesting how some people can withstand or rather tolerate the extremities of some spicy foods where as others act badly and cannot tolerate it.Why does it vary between people if we all have this specific capsaicin receptor?
    (u15089054)

  54. #55 u15084656
    Pretoria
    April 18, 2015

    This is Brilliant. The human Body and how complex it is never ceases to amaze me. I’ve noticed that the more spicy food you eat the more tolerant, towards spicy food, you become. What exactly causes this?

  55. #56 Jovishka Maharaj
    April 18, 2015

    I have always wondered how the burning sensation of peppers were created. It was interesting to read and learn how these receptors react to different substances.
    15045073

  56. #57 Myles Illidge, 14094283.
    April 18, 2015

    I fins it interesting to see how certain (fairly random) substances can be used to understand other substances. In this case the use of spider venom in the capsaicin molecule.

  57. #58 B.S Kramer
    Pretoria
    April 18, 2015

    I would like to start by saying that this comment is with regard to a research assignment for the University of Pretoria. I found this article interesting and enlightening as this was the first time I have heard of the term “capsaicin”. I for one am very tolerant towards spicy foods , and therefore wonder why this varies among people? Is it due to the fact that my taste buds have developed over time and are no longer as affected by the heat/spiciness of the food? I would also like to question how some food/beverages neutralise the burning sensation??
    U15004814

  58. #59 Kim u15147283
    April 18, 2015

    How does the Capsaicin receptor react to people who are allergic to hot or spicy foods? And if it were possible for the receptor to become inactive, what would cause it?

  59. #60 Precious Moloi
    Pretoria
    April 19, 2015

    Very interesting blog! Are these receptors located throughout the body?

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