Enzymes are biological catalysts that play a HUGE role in the chemical reactions that happen around us! The reason why they are so important is because without them, the metabolic processes in our cells won't occur at rates that are fast enough to sustain life! According to Dr. Richard Wolfenden from the University of North Carolina at Chapel Hill, most chemical reactions that occur in nature do not happen without the presence of enzymes because the amount of activation energy that the reactants need to overcome is too great! Without these biological catalysts, reactions that are required to create the building blocks of DNA and RNA will take approximately 78 million years. This means that without enzymes, there would be no life at all!
A. Enzymes are classified into 6 different categories:
These enzymes are normally globular proteins and the sequences of the amino acids ultimately determine the catalytic activity of the enzymes themselves. If you take a look at Figure 2, you will notice that in order for reactants to become products, they need to overcome a high energy transition state. The reason why enzymes are so important is because an uncatalyzed reaction requires a higher activation energy than a catalyzed reaction. Because enzymes can lower the activation energy, reactants won't have to overcome such a high activation energy to become products and thus the rate of the reaction will increases.
If enzymes are so great, you would think that we can just add any kind of enzymes to a substrate and they would bind right? Nope. That's not the case at all. The reason why enzymes won't just bind to any substrates that are being thrown at them is because of their specificity - which makes them particularly picky and won't just bind to any substrates that are dilly-dallying around. ;)
B. SUBSTRATE BINDING: Now, in order to catalyze (speed up the rate of) a reaction, substrates need to bind to enzymes at the active site - a location in the enzyme in which substrates can attached to during chemical reactions. We call this enzyme/substrate compound the enzyme-substrate complex (as seen in Figure 3). When substrates find the active site, ionic interactions, covalent bonds, and hydrogen bonding help stabilizes the spatial arrangement between the enzyme and its substrate. Once the substrate attaches to the active site, the enzyme helps converts it into a product and the product is then released from the active site.
The two different theories that explain the interaction between substrates and enzymes are: The lock and key theory and the induced fit model. In a lock and key theory, enzymes don't have to alter their structure in order for the substrate to bind to its active site. In the induced fit model, however, the binding of substrates to enzymes cause a small amount of free energy to be released. The enzyme starts to alter their conformational structure so that it will increase its affinity to the substrate. In a way, we can say that the binding of the substrate to the active site induces a conformational change in the enzyme so that the enzyme's affinity to the substrate increases (as seen in Figure 4).
C. MECHANISMS OF CATALYSIS: For the most part, enzymes require non-protein molecules called cofactors or coenzymes in order to work properly. Both of them tend to be small in size and are kept at low concentrations so that they can be recruited only when needed. The differences between cofactors and coenzymes are that: 1) Cofactors are inorganic molecules or ions (ie: Fe2+ and Mg2+). Enzymes without cofactors are inactive and are called apoenzymes; 2) Coenzymes include organic groups like NAD+, FAD, Coenzyme A, as well as water-soluble and fat-soluble vitamins. Enzymes with cofactors and coenzymes help create conjugated enzymes called holoenzymes. In the real world, deficiencies in vitamin cofactors can result in diseases that can be life-threatening. For instance, a deficiency in thiamine - a cofactor that is involved in cellular communication and metabolism - can result in Wernicke-Korsakoff syndrome. Patients who suffer from this disorder can have neurological problems and in severe cases, are unable to form new memories.
D. CONTROL OF ENZYME ACTIVITY: The concept of enzyme kinetics can be explained using the Michaelis-Menten Equation, where v is the rate of the reaction, [E] is the concentration of both of the enzymes, [S[ is the concentration of the substrate, [P] is the concentration of the product, and Km is a constant that measures the affinity of the enzyme to its substrate. It is important to remember that changes in enzyme concentration does not affect Km. Higher concentrations of enzymes will result in the reaction to reach the 1/2 Vmax at lower concentration of substrates; while lower concentrations of enzymes will require high concentrations of substrates to reach 1/2 Vmax. If we are comparing 2 different enzymes, just remember that enzymes with lower Km values will require a lower concentration of substrates to be half-saturated while those with higher Km values will require a higher concentrations of substrates to be half-saturated. This means that enzymes with lower Km values have a higher affinity for enzymes and those with higher Km values have a lower affinity for their substrates!
1) COOPERATIVITY: There are certain enzymes, however, that show an S-shaped (sigmoidal) instead of a normal hyperbola. These enzymes are considered to be "cooperative" or "allosteric" enzymes because they have multiple subunits and active sites. Binding of a substrate can cause it to transition from a low-affinity tense state (T) to a high-affinity relaxed state (R). On the other hand, the loss of substrates can cause the enzymes to convert from a relaxed state (R) to a tense state (T). Due to the fact that these enzymes show cooperative kinetics, they often act as regulatory enzymes and are subjected to activation and inhibition.
2) FEEDBACK REGULATION: Enzymes are normally subjected by products in a process called feedback regulation. While it is true that some enzymes may be regulated by feed-forward regulation, most enzymes are regulated by a process called negative feedback (feedback inhibition). These can either increase enzyme-substrate affinity or reduce/inactivate the activity at the active site. Now, you may ask yourself, "Why do we need negative feedback? Isn't the whole point of catalytic reactions is to create more products instead of inhibiting more from being created?" The answer is simple. Imagine this, our body is constantly trying to maintain homeostasis (maintain equilibrium). If we have enough of one product, we want to turn off the pathway so that it will prevent more from being created.
There are 4 types of reversible inhibition: Competitive, noncompetitive, mixed, and uncompetitive.
a. Competitive Inhibition: This is pretty straightforward. If you don't want a certain substrate to bind to the active site, all you need to do is add a competitive substrate (inhibitor) with a similar structure so that it will bind to the active site instead. This inhibition can be overcome if we add more substrate so that the concentration of substrates is higher than the concentration of inhibitors. Because the addition of tons of competitive inhibitors can outcompete the inhibitor, the Vmax value is not affected and the Km value increases. ***Remember that enzymes with higher Km values have lower affinity to their substrates because we require higher concentration of substrates to reach 1/2 Vmax in the presence of the inhibitor.
b. Noncompetitive Inhibition: This is different from competitive inhibition because the inhibitor binds to the allosteric site instead of the active site. Because the inhibitor binds to a non-catalytic region, the two molecules are not competing for the same site and the inhibition is thus considered as noncompetitive. Once the inhibitor binds to the allosteric site, the active site of the enzyme will go through a conformational change that will prevent new substrates from binding to the enzyme. Therefore, we cannot add more substrates to overcome this type of inhibition! Even though noncompetitive inhibitors don't affect the Km value, they do decrease the value of Vmax because less enzymes are available to bind to substrates. Takeaway from this: Enzymes that go through conformation changes due to competitive inhibitors will decrease the number of enzymes that are available to bind to substrates.
c. Mixed Inhibition: Similar to noncompetitive inhibition, mixed inhibitors bind to the allosteric sites instead of the active sites. Interestingly, they have the ability to bind to an enzyme or to an enzyme-substrate complex. If the inhibitor binds to an enzyme, it increases the Km value. If it binds to a complex, however, it lowers the Km value by increasing the enzyme's ability to bind to the substrate.
d. Uncompetitive Inhibition: Uncompetitive inhibitors are unique because they only bind to allosteric sites on enzyme-substrate complexes. This lowers the Km and Vmax values, which means that the enzyme's affinity to its substrate will increase and decrease the number of enzymes that are available to react.
e. Irreversible Inhibition: Unlike reversible inhibitions, in irreversible inhibitions, the active site is either unavailable for a long time or the enzyme is permanently altered and substrates can no longer bind to the active sites. The only way to overcome this is to synthesize more enzymes through transcription and translation.
3) REGULATED ENZYMES: These enzymes are often parts of biological pathways like glycolysis and the Kreb Cycle. There are 3 different types of regulated enzymes: Allosteric enzymes, covalently modified enzymes, and zymogens.
a. Allosteric Enzymes: These enzymes have multiple binding sites and alternate between an active and inactive form.
b. Covalently Modified Enzymes: Enzymes that can be activated or deactivated by phosphorylation, dephosphorylation, or glycosylation.
c. Zymogens: Enzymes that are secreted in its inactive form and are activated by cleavage. An example of trypsin, which is an enzyme that is released from the pancreas. It is secreted as trypsiniogen because without being controlled, this enzyme will digest the organ itself.
B. IMMUNE SYSTEM: The high degree of protein variability allows for a key feature of the adaptive (or acquired) immune system, the production of antibodies. An antibody is a type of protein that has a unique and very specific binding site that will readily bind its target, called an antigen, such that its target is inactivated or tagged for immune response.
C. MOTORS: A motor protein can perform mechanical work by coupling exergonic (energy releasing) ATP hydrolysis to a conformational change that allows for interaction with the protein's target substrate. Muscle contraction, for example, is achieved through a process of the motor protein myosin binding and releasing its microfilament (actin) substrate. Myosin also acts on microfilaments of the cytoskeleton to generate cellular movement.
Two other types of motor proteins, kinesins and dyneins, act on microtubules and play a role in transport within the cell. Kinesin walks microtubule "tracks" to deliver cellular cargo (e.g. chromosomes during mitosis, vesicles), generally in an antegrade direction (center to periphery). Dynein is used in retrograde cargo transport in the axons of neurons, and is capable of sliding microtubules in relation to one another, generating the movement of cilia and flagella.
Let's do a quick recap! Basically, we have learned that enzymes:
If you haven't read part 1 and 2 of this series yet, I will put the links here and here for you! For this segment, we will talk about peptide bond formations and the 4 different types of protein structures. Now, if you've already known about amino acids, you will know that they are the building blocks that make up peptides and proteins. However, how do they come together to create these peptides? The answer is something called "peptide bonds".
Proteins are linear polymers of amino acids (monomers of protein) or "residues". When there are 2 amino acids "bound" to each other, we call them dipeptides. When there are 3, they are called tripeptides. And when there are more AAs subunits/residues being bind to each other, they are called polypeptides. These peptides are actually joined together by peptide bonds, which is a covalent amide that is formed between the carboxylic group (-COO-) of one AA and the amino group (-NH3+) of another amino acid.
FOUR TYPES OF PROTEIN STRUCTURES
Proteins have 4 levels of structure: Primary, secondary, tertiary, and quaternary.
A. Primary Protein Structure: The primary structure of a protein is basically the sequence of amino acids that's stabilized by the formation of covalent peptide bonds between the adjacent amino acids. The primary structure of the protein is determined the gene that corresponds to that protein. The linear amino acid sequence is important because it helps determine the native conformation of the protein. The free amino end at the left that has NH3+ is called the N-terminus and the free carboxyl end at the right is known as the C-terminus (COO-).
PEPTIDE BOND FORMATION
Peptide bond formation is the result of a dehydration synthesis reaction. First, the electrophilic carbonyl carbon on the first AA is attacked by the nucleophilic amino group on the second AA. Then, the hydroxyl group of the carboxylic acid is kicked off and this results in the formation of the peptide bond. To make it short and sweet, the carboxyl group of one molecule will attack the amino group on the other amino acid - releasing an H2O molecule (some water) as a byproduct. You now have a dipeptide!
HOW TO BREAK UP PEPTIDE BONDS
Peptide bonds can be broken in processes called hydrolysis and proteolysis. This can either be done with proteolytic enzymes or strong acids. Let's say you throw the polypeptide in a strong acid solution with some heat, then you will get a bunch of broken up amino acids in the mixture. It's therefore considered to be nonspecific because it doesn't discriminate where it cuts. If you add some proteolytic enzymes, however, they will cleave up the peptide bonds only at specific locations. Proteases don't just cleave anywhere. Oh no no no. Just think of them as being the pickier friends/cousins to strong acids. ^^ For example, trypsin, an enzyme that's produced by our pancreas, only cleaves at the carboxyl side of basic amino acids like lysine, arginine, and histidine. Therefore, if there's a polypeptide chain with those basic amino acids, they will cleave the right side/C-terminal of those side chains!
B. Secondary Protein Structure: A protein's secondary structure is held together by the intramolecular hydrogen bonding between the amino acids that are nearby. The 2 most common secondary structures are alpha helices and beta pleated sheets.
1) Alpha Helices: An alpha helix has a rod-like structure that coils clockwise around a central axis. The side chains are pointing away from the helix core. It's an important structure in keratin, the protein that is found in our hair, skin, and fingernails!
2) Beta Sheets: Beta pleated sheets are composed of parallel or anti-parallel peptide chains that lie alongside one another. They are held together by hydrogen bonds between the carbonyl oxygen atom of 1 chain to the amide hydrogen atom in the adjacent chain.
***Amino Acids that Interfere with Secondary Structures :
Proline: Due to its rigid structure, proline is rarely found in alpha helices and beta sheets because it introduces kinks in the structures. The reason why is because its side chain forms a second alkyl group to the amine. This causes the structure to have conformational rigidity and in return, it cannot act as a donor for hydrogen bonding. Interestingly enough, although proline introduces kinks to secondary structures like alpha helices, it can be commonly found in helices that cross the cell membrane as well as in between turns between the chains of a beta sheets.
Glycine also applies as well. However, I already explained about it so feel free to go back to part 1 of this series to read more about it!
C. Tertiary Structure: The tertiary structure of a protein has a 3-dimensional shape that is determined by hydrophobic and hydrophilic interactions between the AA's R groups. Because of their nature, hydrophobic AAs prefer to be in the interior of proteins and hydrophilic AAs prefer to be on the surface of proteins. An important component of tertiary structures is the presence of disulfide bonds, which can form when 2 cysteine molecule goes through the oxidation reaction (where 2 protons and 2 electrons are lost) to form cystine. These disulfide bonds create loops in the protein chain.
D. Quaternary Structure: These protein structures normally contain more than 1 polypeptide chain and they reflect the final composition/form of the protein. You can just imagine lots of tertiary structures coming together to create a quaternary structure if that makes it easier! Examples that we can find in our daily lives include hemoglobin as well as immunoglobulin G (igG) antibodies. They are held together by non-covalent interactions and tend to be: 1) More stable due to the reduced surface area; 2) Reduce the amount of DNA that's needed to encode the protein complex; 3) Bring catalytic sites closer together and thus speed up reactions; and 4) Induce cooperativity or allosteric effects.
E. Protein Folding and Denaturation
Now that you have a better understanding of protein structures and peptide bonds, let's go ahead and discuss HOW and WHY they conform a certain way! Have you ever questioned why not all proteins look alike? The answer has to do with something called hydrophobic interactions.
*** Non-covalent Interactions:
For a quick recap, in primary structures, the amino acids are held together by peptide bonds. In secondary structures, they are held together by hydrogen bonds. In tertiary and quaternary structures, the polypeptides are held together by something called hydrophobic interactions, which play an important part in a protein's conformational stability. It can come from van der Waals forces between nonpolar side chains as well as London dispersion forces.
1) Protein Folding and the Solvation Layer:
Okay, let's break it down: First, you need to know that hydrophilic residues like to accumulate on the surface of protein structures and hydrophobic residues occupy the interior of the proteins. For example, if you drop a hydrophobic solute into an aqueous solution, that solvent will form something that's called a solvation layer around that solute. Because of its polarity however, the water molecules in that solvation layer cannot form hydrogen bonds with the side chain. This means that the H2O molecules will have to rearrange themselves in order to maximize the number of hydrogen bonds between the solvent and the solute. Therefore, there will be a negative change in entropy and this makes the overall process non-spontaneous. On the other hand, if we put a hydrophilic solute into a polar solvent, the water molecules will have an easier time forming hydrogen bonds with the side chain and it will try to arrange itself so that the number of hydrogen bonds will be maximized. This increases the entropy and make the overall process spontaneous.
2) Protein Denaturation:
Think of this process as the opposite of protein folding. It is often irreversible and unfolded proteins cannot catalyzed reactions. For instance, when temperature increases to a high enough temp, then it can overcome the hydrophobic interactions and causing it to denature (unfold). This happens a lot in cooking. I mean, heat ==> increase in temperature ==> protein denaturing! Science is amazing guys (cue what Ash says in almost every single episode of Pokemon). ^_^ Besides heat, solutes like urea and SDS can also denature proteins by disrupting the disulfide bridges or the non-covalent bonds that hold the proteins together! Therefore, these solutes are often used to break up protein compounds.
This is the 2nd installment for amino acids and protein structures. If you haven't seen my first post about amino acids or AAs, please click on this link right here! Now that we got that out of the way, let's move onto the article.
Last week, we talked about nonpolar amino acids. This week, our main topic will be about polar amino acids! There are 2 different types of polar amino acids: Charged and uncharged.
**NOTE: When I refer to the physiological pH, I mean that the pH is approx 7.4. Also, when something is deprotonated or protonated, it means that there's either a removal or an addition of a proton to the molecule.
A. POLAR ACIDIC AMINO ACIDS
1. Aspartate or Aspartic acid (asp, D) has a carboxyl group in its side chain. It is negatively charged at a physiological pH because its side chain has a low pKa of 4.0 and therefore tends to be deprotonated.
2. Glutamate or Glutamic acid (glu, E) also has a carboxyl group in its side chain. Like aspartate, this group has a low pKa and is prone to deprotonation. It is therefore negatively charged at a physiological pH of 7, Because of these reasons, aspartate and glutamate are known as "acidic" amino acids. They play an important role in maintaining the solubility/ionic characters of proteins. Unlike aspartate however, glutamate has one additional methylene group in its side chain. The inductive effect of the additional methylene group causes the pKa value of glutamate to be at a 4.3 instead of 4.0.
B. POLAR BASIC AMINO ACIDS
1. Histidine (his, H) is an essential amino acid that cannot be made by the body. It has an imidazole group in its side chain that has a pKa value of approx 6. Because of its pka value, it can either be protonated or deprotonated. This allows this unique amino acid to act either as a general base (hydrogen acceptor) in its deprotonated state or as a
general acid (hydrogen donor) in its protonated state.
2, Lysine (lys, K) and Arginine (arg, R) are both essential amino acids. They have have nitrogen-containing groups in their side chains, with lysine having an amino group and arginine having a guanidine group. These groups have high pKa values, with lysine having a pKa value of approx 10.5 and arginine having a pKa of approx 12.5. Because they are positively charged at the physiological pH, lysine, arginine, as well as histidine, are known as "basic" amino acids. In proteins, they tend to interact electrostatically with negatively charged groups like aspartate and glutamate.
**NOTE: I will delve a little bit deeper into the noncovalent R group interactions in another post. So stay tuned for more!
C. POLAR UNCHARGED/NEUTRAL AMINO ACIDS
1. Cysteine (cys, C) is a sulfur-containing amino acid and it has a thiol (sulfhydril) group in its side chain. Because it has such a mild polarity, although cysteine is polar, it is considered to be hydrophobic and NOT hydrophillic. This amino acid can react with another cysteine to form a disulfide bridge. This plays a large role in stabilizing different proteins; like the ones that act as digestive enzymes in the small intestine.
2. Serine (ser, S) and threonine (thr, T) – have a hydroxyl group in their side chain. The only difference between threonine and serine is the fact that threonine has an extra methyl group in place of a hydrogen on the β carbon.
3. Glutamine (gln, Q) and asparagine (asn, N) – have an amide group in their side chains. Because of their unique structure, both of these AAs are usually involved in hydrogen bond networks within different proteins.
4. Tyrosine (tyr, T), like phenylalanine and tryptophan, are considered to be aromatics. This essential amino acid is hydrophobic and has a hydroxyl group (-OH) at the para position.
If you are into supplements and protein powders, I'm sure you have seen packages with the word "amino acids" on them. For those who don't know what they are, amino acids (AA) play an essential role in the human body; acting both as the building blocks of peptides and proteins as well as precursors in metabolic pathways. Proteins that are formed from these AA have distinct three-dimensional structures and sequences that allow them to have different roles in various biological and chemical processes.
Only 10 out of the 20 AA can be produced by the human body. They are: Alanine, asparagine, aspartate, cysteine, glutamate, glutamine, glycine, proline, serine and tyrosine. The other 10 amino acids that we need to obtain from our foods are: Histidine, isoleucine, leucine, lysine, methionine, phenylalanine, threonine, tryptophan, and valine. These are considered to be essential amino acids because we HAVE to obtain them from different foods.
The reason why we call them "amino acids" is because each structure contains two distinct functional groups. An amino acid has a central chiral carbon called the alpha carbon (Cα), a hydrogen atom, an amino (-NH2) group, a carboxylic acid (-COOH) group, as well as a variable side chain (R).
**Be aware that because of the intramolecular acid-base reactions, a proton is transferred from the carboxyl group to the amino group to produce a zwitterion (dipolar ion). Therefore, an amino acid normally has an NH3+ group on one end and a COO- group on the other end!
1) Amino acids are crystalline solids with high melting points. They are generally soluble in water and are insoluble in nonpolar solvents.
2) The carboxyl group has a low pKa of 2 and is negatively charged at physiological pH. The amino group, on the other hand, has a high pKa of approx 9-10 and therefore is positively charged at the physiological pH.
3) When we say that amino acids have chiral carbons, what it essentially means is that these amino acids are optically active molecules. Therefore, if you shoot a plain, polarized light at these AAa, they will rotate to that light.
***Note: Out of all the AA, only glycine is not optically active. Explanation below.
There are 20 standard amino acids and they all have very unique side chains that make them distinctive from one another. In order to make it a little simpler, we can divide these amino acids into 2 different categories: Hydrophobic (water-hating) and hydrophillic (water-loving). Amino acids that have nonpolar R groups are hydrophobic and will bury inside the proteins so that they can stay as far away from water as possible. AAs that have polar side chains, on the other hand, will fold themselves so that their R groups will be on the surface so that they can interact with other water molecules.
A. NONPOLAR HYDROPHOBIC AMINO ACIDS
1) Glycine (gly, G) is a unique amino acid because it only has a hydrogen as its "R group" - making it the smallest AA out of the 20 standard ones that we will be discussing about today. Because it has 2 different hydrogen atoms - one that already attaches to the backbone and another one that attaches to the side chain, this means that the AA is symmetrical and thus is achiral. Because of its high conformational flexibility, glycine favors the unfolded conformation over the helix conformation and is considered as a "helix breaker".
2) Alanine (ala, A) has a methyl (CH3) group as its side chain. Interestingly enough, it's also the analog of the α-keto acid pyruvate - an intermediate in sugar metabolism.
3) Valine (val, V) has an isopropyl R group.
4) Leucine (leu, L) has an iso-butyl side chain. What this means is that it has a similar side chain to valine, but with an extra CH2 group.
5) Isoleucine (Ile, I) is an isomer of leucine and has sec-butyl instead of iso-butyl as its side chain. Since our body cannot synthesize this AA, we need to obtain it from foods such as eggs, poultry, fish, and soy products.
6) Methionine (met, M) has a sulfur that's embedded in its linear aliphatic side chain (also known as the thioether side chain). Now, you may think that it's a polar AA because of the sulfur. However, if you look at where it's located, you will see that it is partially hidden and that the difference in electronegativity is extremely small! Foods that consist high levels of methionine include eggs, seeds, fish, and meats.
7) Proline (pro, P), unlike other AAs, is the only one that has the backbone in its side chain. The 3-carbon chain from the alpha carbon loops around and attaches itself to the amino group. Because it doesn't have a hydrogen on the alpha amino group, it cannot donate a hydrogen bond and thus cannot stabilize an alpha helix or a beta sheet. Because of its unique structure, alpha helices that have this AA often have "kinks"" as a result. Proline, along with glycine, are known as "helix breakers".
8) Phenylalanine (phe, F) is an essential amino acid that cannot be synthesized by the body. Because of its hydrophobicity, this AA always bury itself inside of a protein.
9) Tryptophan (Trp, W) is another essential amino acid that we must obtain from foods. At a glance, it almost looks like a polar amino acid. However, if you take a closer look, you will see that the N-H bond makes up a very small part of a rather large side chain. The electrons from the nitrogen is so integrated into the side chain of the tryptophan that it doesn't really interact with water molecules.
Have you ever taken a bite from a dish only to discover that your mouth is on fire? When we eat dishes that contain ingredients like chili peppers or jalapenos, the first thing that come to a lot of people's mind is, "Dang, that food is SPICY!" And what exactly "makes" the food taste spicy? Do we taste spiciness the same way that we taste sweet or salty foods? The answer is No. No, we don't.
Lining our tongues are thousands of pink colored bumps called papillae. Within each papillae are thousands of taste buds that contain numerous sensory cells, which in essence, can function as fluid-filled funnels/channels. These cells, along with our olfactory sense and trigeminal nerve fibers, help us differentiate between the 5 basic tastes: Sweetness, sourness, bitterness, saltiness, and savoriness/umami, Contrary to what a lot of people believe, spiciness is actually not triggered by the sensory nerves in the taste buds. The burning sensation is actually induced when plant-derived compounds like capsaicin from chili peppers activate trigeminal nerves that express the TRPV1 receptors. The direct activation of these nerve fibers cause the somatosensory fibers that are located on the tongue to interpret this as "hot" or "spicy".
WHAT EXACTLY IS CAPSAICIN?
Capsaicin (CAP) is a term that was first coined by a chemist named Christian Friedrich Bulchoz. It's an active and pungent chemical compound from chili peppers and has been studied extensively since its discovery back in 1919. This molecular compound, also known as 8-methyl-N-vanillyl-6-nonenamide (C18H27NO3), belongs to a class of compounds called capsaicinoids and can trigger the pain receptors that are located on the tissues in your body.
OUR BRAIN ON CAPSAICIN
Spicy foods can excite pain receptors on the skin that normally respond to heat. These receptors, also known as polymodal nociceptors, respond to extremes in temperature, mechanical stimulation, and chemicals that are flowing through our central nervous system (CNS). When we eat spicy foods, capsaicin binds to vanilloid receptors called VR-1 and TRPV1 that are located on the nerve endings of C-fibers.
In the absence of capsaicin, these ligand-gated ion channels (VR-1 and TRPV1) are normally closed. However, when the capsaicin binds to these receptors, they start opening up and an influx of sodium and calcium ions enters these channels. An action potential is initiated and the neural signals that originate from the terminals of the receptors are propagated to second-order neurons in the CNS. It triggers other nerve cells and not only cause the brain to think that the body is being exposed to a dangerously high temperature, it also stimulates the nerves that respond to mild increases in temperatures as well. These are the reasons why capsaicin makes our tongue feel like it is on fire!
*Quick Note: Since TRPV1 is present on nerve cells all throughout the body, it is essential that you wash your hands after touching chili peppers. Don't touch your eyes or other parts of your body that you WOULD NOT want to burn!
Now, we know that the capsaicin in spicy peppers can cause a burning sensation on our tongue, mouth, and anywhere that it touches. If it's so painful, why do we keep eating it?? The main reason why is because capsaicin tricks the body into thinking that it's being burnt. However, because our body is trying to protect itself, the brain responds by releasing endorphins - which are peptide hormones that are produced by the CNS and the pituitary gland, as well as dopamine - a neurotransmitter that plays a major role in the reward/pleasure behavior. Basically what happens is that it depletes the neurotransmitter of painful impulses known as substance P from the sensory nerve terminals. Therefore, whenever you eat lots of spicy food, we start to experience a sense of euphoria and elation that is similar to a "runner's high".
HOW TO DEFEAT THE HEAT!
If you love spicy foods but cannot handle the heat, then dairy products can definitely help lessen the burn! Normally, when people eat something that's too spicy, the first thing they should do is to take a big gulp of water right? WRONG. NOPE. Don't do it. I repeat, DON'T DO IT. Water will only make it worse. If you take a look at the chemical structure of this pungent compound, you will notice that capsaicin has a long hydrophobic/hydrocarbon tail. Hydrocarbons tend to be nonpolar and have negatively charged electrons and positively charged protons evenly distributed throughout. Therefore, when you drink milk, eat ice cream, or any other dairy products that contain nonpolar molecules, they will attract and surround the capsaicin molecules, effectively soothing the burn that plagues our tongue!
On the other hand, water is a polar molecule. This basically means that it leaves the oxygen side of water with a partial negative charge and the hydrogen side with a partial positive charge. One side of the polar molecule will develop a partially negative charge while the other will develop a partially positive charge when it binds to atoms with higher electronegativity. Thus, when you drink water, it will only spread the capsaicin oil around our mouth, making the pain worse.
REAL WORLD APPLICATIONS
Due to the effects that it has on the human body, scientists have been studying capsaicin's biological responses and its mechanisms in dealing with conditions such as rheumatoid arthritis, neuralgia, diabetic neuropathy, as well as other syndromes that deal with the central and peripheral nervous systems. In many randomized and double-blind studies, researchers have found that while the topical application of lower concentrations of capsaicin (approx 1.5% to 7.5%) can be an effective treatment for osteoarthritis pain, the transient application of higher concentrations of capsaicin (around 8%) helps reduce neuropathic pain. When capsaicin is being applied topically or injected into the skin, it will also lead to the desensitization of the A-fiber and C-fiber nociceptors (afferents that are responsible for the pain from capsaicin) to heat stimuli as well.
I'm Linh - a science geek who loves experimenting and tinkering with recipes! I hope that this blog brings more ideas into your kitchens! Happy eating folks! XOXO