Suicide Wings: A Capsaicin Experiment

It all started as a slight, barely noticeable tingle a few seconds after I took my first bite into a suicide wing at a local bar. The spiciness was a bit uncomfortable, but it wasn’t nearly as awful as everyone made it out to be. A few seconds passed, and the burning slowly intensified. Okay, maybe it was a bit spicy, but I can handle it; I’ve had worse. I gave it a few more seconds and that is when the burning really started to escalate; my forehead and hands started to sweat, my tongue felt like it was on fire, and tears started to run down my face. I have made a serious mistake, I thought to myself. Why did I think eating a suicide wing was a good idea? Five minutes and a dozen glasses of water later, the pain finally began to subside. But, for some reason I still do not understand, I took another bite into the wing from hell. Except this time, things seemed different. Although the wing was still spicy, it didn’t seem nearly as spicy as the first time. It felt like my tolerance for pain had increased since the first bite. As an aspiring biochemist, I was naturally curious, so I set out to learn what had happened to my spice sensitivity and why.

The first thing I discovered on my figurative journey was that the fiery feeling in my mouth was due to a molecule known as capsaicin. This molecule and other related molecules (commonly referred to as capsaicinoids) are found in the peppers from plants in the genus Capsicum. Capsaicinoids are produced by the peppers in order to aid in the dispersal of seeds. Plants in this genus use birds as a dispersal method for the seeds, as birds will not damage the seeds by ingesting the peppers. In contrast, seed damage and loss of viability commonly occurs during the consumption of the peppers by mammals. Birds are not affected by capsaicin, but mammals are. Thus, the production of capsaicin deters mammals from consuming the peppers, but birds can consume the fruit without adverse effects.

My second discovery was that capsaicin, and capsaicinoids in general, produce their fiery effects by acting as an agonist for the vanilloid receptor subtype 1 (TRPV1) receptors. These receptors are found on sensory neurons and are responsible for the recognition of heat, the regulation of temperature, and the sensation of pain. When the TRPV1 receptors are exposed to high temperatures (above 42⁰C), the cell depolarizes due to the rapid influx of extracellular calcium ions. This rapid influx of ions initiates a signal transduction pathway and elicits many physiological responses, one of which is a painful burning sensation (See figure 1). This sensation is due to the transmission of a signal from the TRPV1 receptors to the nervous system which, among other things, results in neurogenic inflammation, vasodilation, and an increased heart rate. The transmission of this signal is mediated primarily through two neuropeptides: substance P (SP) and calcium gene-related peptides (CGRP). As an agonist, capsaicin interacts with the TRPV1 receptors such that they are activated and the signal transduction pathway ensues. This means that when I took a bite out of the chicken wing, my mouth felt like it was burning when, in reality, the burning sensation was due to the interaction between capsaicin and the TRPV1 receptors. So, that explains the initial displeasure that I felt after the first bite, but what about the reduction in my sensitivity following the second?

Biochem sem blog picture

Figure 1. Capsaicin binding to the TRPV1 results in the influx of extracellular calcium ions. This influx initiates a signal transduction pathway resulting in the release of the neuropeptides substance P (SP) and calcium gene-related peptides (CGRP). The influx also activates a calcium/calmodulin dependant enzyme.

 

Although capsaicin initially causes a burning sensation through the release of SP and CGRP, exposure to the molecules over a longer period of time results in the desensitization of the sensory neuron. This desensitization, which lasts well over two hours, leads to a significant decrease in pain. The desensitization of the TRPV1 receptor explains why my first bite of the suicide wing felt blistering hot, but the second wasn’t nearly as painful. Although researchers agree upon the idea that desensitization occurs following long term exposure to capsaicin, the exact mechanism is still debated. There are currently two theories as to how the desensitization occurs, but recent research suggests that a combination of both theories may be correct. The first theory involves the blocking of SP and CGRP. The second theory involves the failure of the cell to repolarize following the influx of calcium ions.  Some researchers believe that the continued activation of the TRPV1 receptor by capsaicin causes the inhibition of the voltage-gated channels responsible for the release of SP and CGRP, which decreases our ability to sense pain. Other researchers believe that the continued activation of the TRPV1 prevents the repolarization of the cell through the continued stimulation of a calcium/calmodulin-dependant enzyme. The continued stimulation of this enzyme results in the dephosporylation and deactivation of many different proteins involved in the TRPV1 signal transduction pathway. In either case, the constant stimulation of the TRPV1 receptors by capsaicin causes desensitization. Therefore, capsaicin has proven to be useful as an analgesic! This point leads me to my final discovery.

Capsaicin has been utilized in a variety of different ways, with two major applications being mace (pepper spray) and as an analgesic. It is used in mace as an eye irritant that is very painful but does not pose any serious health effects. Capsaicin is also utilized as an analgesic for the treatment of ailments such as arthritis, sore muscles, sprains, strains, and bruises. It is most commonly used in topical ointments such as Icy Hot. Although capsaicin is mainly used as an external ointment, researchers have demonstrated that it can also be used through direct injection in order to treat chronic nerve pain. Current research is focusing on new and innovative uses!

When I took my first bite of the suicide wing, I would have never imagined that it would be the catalyst to learning about capsaicin, the TRPV1 receptor, and desensitization. I most certainly did not expect to learn that capsaicin is commonly used in pepper spray and as an analgesic! But that is the great thing about life: we may not necessarily set out to learn new things every time we try something new, but with a curious mind and a positive attitude, we are bound to learn something!

Happy Reading,

E

The Magic of Miraculin

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What if I told you I can make a lemon turn in to an orange? Ok, maybe I can’t do that, but what if I said I could make the lemon taste like an orange? Now that I can do! Making a lemon taste like an orange can be easily accomplished through eating a protein known as miraculin. Miraculin, for those who are curious, is a protein found in the fruit of the plant called Synsepalum dulcificum, which is found in areas in western Africa. When you eat this fruit, everything that should taste sour will instead taste very sweet. You may be asking yourself how a lemon tastes like an orange after eating this protein. Well, I can help you with that! But be warned, things may get a little complicated!

Before we dive in to how miraculin works, let’s take a step back and first look at how we taste in general. There are 5 main categories of taste that are referred to as sweet, sour, salty, bitter, and umami. Up until the 1980’s there was a common misconception that these five categories of taste are localized to specific areas of the tongue, and that simply isn’t true.  In reality, we are able to perceive any of the five categories of taste all over the tongue, but there are some areas that are more sensitive to specific tastes than others. This is due to the density of specific receptors in different areas on the tongue; where a greater receptor density results in an increased sensitivity to a particular taste.Picture1

Now that we’ve got that straightened out, let’s talk about taste buds. Taste buds are composed of many different types of cells which work together to provide us with a sense of taste. There are three main cell types found in a single taste bud: gustatory cells, sustentacular cells, and basal cells. Gustatory cells are responsible for initiating the signal transduction pathway responsible for taste, so this is where our focus will lie. The signal transduction pathway begins at structures known as gustatory hairs, as these hairs contain the receptors that interact with food. The gustatory hairs are exposed to the inside of our mouths, and the molecules from the food we eat washes over the gustatory hairs. These molecules then interact with the gustatory hairs, resulting in the initiation of a signal transduction pathway. The other ends of the gustatory cells are adjacent to afferent neurons, and the signal which originated from the gustatory hairs travels to the neurons and follows the afferent neural pathway to our brains. Our brains then interpret this signal and the result is our perception of taste.  Now, this is a general explanation for taste; the mechanisms for each of the 5 categories of taste differ significantly from one another. For example, the receptor responsible for the perception of sweetness, known as T1R2-T1R3, is a 7 transmembrane receptor (7TM). This 7TM receptor interacts with many carbohydrates which, ultimately, results in us tasting sweetness. In contrast, the receptor responsible for the perception of salt is not a 7TM receptor but an ion channel known as an amiloride-sensitive sodium channel. These ion channels detect the difference in membrane potential due to an increase in sodium ions (salt), and this change in membrane potential results in our perception of salt. Now that we’ve gotten a taste of how we perceive flavours (sorry, I couldn’t resist!), let’s look at to how miraculin works!

Miraculin is a small glycoprotein that forms a tetramer in the fruit.  This protein, when eaten, interacts with the T1R2-T1R3 receptor in an antagonistic sense. In normal circumstances, like when we eat an apple, the carbohydrates interact with T1R2-T1R3 as an agonist, resulting in an initiation of a signal transduction pathway and a sweet taste in our mouths. In contrast, miraculin acts as an antagonist such that the T1R2-T1R3 receptor is blocked and cannot initiate the signal transduction pathway, thus preventing us from tasting sweetness. Well wait just a minute. Didn’t I say it made things taste sweet, not prevent it? Hang with me here; this is where things go a little… sour. At the pH of our mouths, which is in the range of 6.2-7.4, miraculin acts as an antagonist; however, when we eat something sour (like a lemon), the natural acidity drastically drops the pH in our mouths, and miraculin begins to act like an agonist.  This transition from antagonist to agonist is due to a change in the conformation of miraculin, which is a result of the increased acidity. The change in conformation is, in turn, due to two histidine residues present on miraculin. At the normal pH of our mouths, these two histidines in miraculin have a net neutral charge, and in this conformation, miraculin interacts with the T1R2-T1R3 receptor such that no signal initiation occurs. At a decreased pH, however, the two histidines pick up protons and gain a net positive charge. As a result, the conformation of the protein changes such that the two histidines are capable of interacting and activating the T1R2-T1R3 receptor. So, what does this mean? After eating Synsepalum dulcificum, everything that should taste sour will wind up tasting very sweet due to the effects of low pH on miraculin. The effects only last an hour or so, so don’t get too worried about losing your ability to taste sour things! Putting all of this aside, you may be asking if miraculin has any practical uses apart from being a cool party trick. It turns out that many researchers have been developing ways to use miraculin for practical uses. Researchers hope to use miraculin as a low calorie alternative to sugar for people who have diabetes and for people who are simply trying watching their weight.

All in all, miraculin is a pretty cool protein with some interesting effects, and if you ever find yourself face to face with Synsepalum dulcificum, give it a try! Who knows, you may find the experience pretty… sweet.

Happy Readings,

E

A Brief Beginning

Sour, sweet, bitter, salty, and umami; the five distinct categories we can perceive as taste. And, according to essentially every image available on Google, each of these five elements have a corresponding area on the tongue. Of course, because it’s on Google, it must be true.  I mean, Google couldn’t possibly be wrong! If you dig a little bit deeper, however, you may (or may not) be surprised to find out that the whole “corresponding area” thing is a load of B.S. After realizing that Google has lied and can no longer be trusted, how can anyone believe anything on the internet?! Thankfully for you, this blog will be full of interesting, cutting edge science!  Specifically, I will be diving into the interesting topic of taste! What are taste buds (apart from being buds that taste)? How do they work? Is it possible to alter how they work?  All of these topics and more will be discussed in this blog!