BIOC 223

After catching a cold this week, I began searching for remedies that could shorten the duration of my symptoms. I found the usual suggestions- sleep, drink water, take vitamin c, and eat a balanced meal. However, I surprisingly came across websites that suggested taking zinc supplements. Although these websites stated it is best to take the supplements at the onset of symptoms, Zinc can interfere with the ability of the rhinovirus to reproduce and blocks their ability to dock on cell membranes, preventing infection.  Yet, there were also websites that downplayed the benefits of Zn. Which made me realize that these biological studies on viruses are always ongoing. But then when can we definitely claim an experimental result is true?

I am not sure what the outcomes will be by taking a Zn supplement, but if I get desperate enough to get rid of this cold I’ll make sure to mention the results.

We’ve been talking about thiols and disulfide bonds a lot lately and it’s been super useful for my research. I rely a lot on thiol reactions in my research since thiols stick really well to gold. Sulfur-gold reactions are semi-covalent, with a strength of about 45 kcal/mol, which is ideal since we want to attach all the components to the gold as strongly as possible. To get everything attached on the gold, we have to introduce a free thiol on to each component but make sure that the thiols don’t form disulfide bonds. So today’s lesson on pH and pKa in thiols was an especially important and really useful!

Having just attended to the Widow’s Spring teaser, their musical talents has inspired me. I looked into the possibility of connecting biochemistry and music.

http://www.oregonlive.com/living/index.ssf/2013/01/there_once_was_a_man_from_corv.html

According to Professor Kevin Ohern at the Oregon State University, these two very different topics can be united to make musical biochemistry. He teaches a lot of the biochemistry material, including learning the 20 amino acids and the functions of amino acids using popular songs (including tunes from the Beatles and a parody of YMCA). There is a strong correlation between musical sounds and memory, and music brings back memories. Using this technique maybe biochemistry won’t be as daunting as predicted by other students in the past. It can fun and engaging as well!

So as a biochemistry major, I’m (as I’m sure all of us are) a sucker for finding cool ways to apply advanced chemistry concepts to biological molecules. Right now in Orgo II we’re studying aromaticity, and one of the first concepts we learned the other day was Huckel’s Rule. This rule states that if a cyclic, planar, fully conjugated molecule has 4n+2 pi electrons (where n can be any integer including zero), it is considered aromatic. The other part of this rule is that if a cyclic, planar, fully conjugated molecule has 4n pi electrons, it is considered anti-aromatic. Furthermore, an important concept to remember when dealing with aromaticity is that an aromatic compound is most stable when it is in its aromatic form, or in other words, is extremely unreactive if its aromaticity is being compromised. Anyway, in our pset due this morning we had a problem that asked for us to (1) determine whether the imidazole ring in the histidine side chain was aromatic and (2) to explain how this information could help us determine which of the two nitrogens in the ring gets protenated. If we look at the deprotenated imidazole ring on histidine (below), we can see that there are 6 pi electrons available in the ring. These 6 electrons come from the two double bonds and the lone pair of electrons belonging to the NH. We can therefore say that the ring is aromatic, since 4n+2=6, where n=1. When determining which of the two nitrogens will accept a proton, we have to now consider which nitrogen could compromise the aromaticity of the ring. The lone pairs on the NH belong to the 6 pi electrons that make the  ring aromatic so if a proton were to be accepted by this nitrogen these electrons would be removed and the ring would be left with 4 pi electrons and since 4n=4, when n=1, the ring would become antiaromatic. A reaction that removes a ring’s aromaticity is extremely unfavorable. However, the other nitrogen’s lone pairs do not belong to the pi electrons in the ring and can therefore be used to accept a proton, hence why we see that that nitrogen gets protenated (below). Pretty cool!

…speaking of Crystallography’s birthday, I remembered that when Pam Melroy was here she spoke of protein crystals in space, and experiments going on in the space station.

A quick google search led me to a UAB Magazine article, with the great intro: “It was a small step for man, but a giant leap for protein science when UAB researcher Larry DeLucas, O.D., Ph.D., shot into orbit aboard the space shuttle Columbia on June 25, 1992. DeLucas—the first optometrist in space—conducted experiments on protein crystal growth that were an important step in the drug discovery process for treating AIDS and other devastating diseases.”

According to this article DeLucas has become a world-famous crystallographer, winning several awards for this work.

If my memory serves me right, the reason crystallography is made faster in space is because of the lack of Force of Gravity.

In the absence of gravity, I suppose the total volume of proteins would change…If the bonds are spaced further apart, would that mean new conformations, impossible on earth, could exist in space?

https://www.uab.edu/uabmagazine/breakthroughs/research/proteins-in-space

Yesterday in my Women’s and Gender Studies course, we were talking about birthing and delivery methods. Interestingly, C-sections have correlated with higher rates of health problems, such as autoimmune disease and allergies, in babies than those born through other methods. Though the studies are not definitive (http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3110651/) they pose policy-changing implications.

The mother passes her antibodies to the fetus during the last three months of the pregnancy. Antibodies are just large proteins that our immune system employ to identify foreign material such as viruses and bacteria (and we also use antibodies in protein tagging experimentally!). During more traditional birth methods, the mother also passes bacteria and some of these foreign materials to the baby as he leaves the birth canal, which help him develop his own antibodies. C-sections lack this introduction of foreign matter to the baby’s immune system early in his life, which may be the cause for a weaker immune system and health problems.

After getting sick this week, I’ve been eating poorly and taking medicine, culminating in a period of heartburn last night. Trying to placate my stomach, I turned to the internet and found that it’s probably because I’m eating too many acid-inducing foods! Who knew that pH would factor into such a mundane and frequent event as eating? What I read was very interesting – it turns out that it isn’t the pH of foods that make it acidic or basic for your body. Rather, it is the acidity of the final products after digestion that one’s body takes up that determines how acidic your body considers it. An interesting example are lemons, which are very acidic but end up as alkaline forming after being ingested. Apparently many people are very concerned about balancing their bodies’ pH through food, as there have been many studies and even an “alkaline diet” claiming health benefits. One such study I found below:

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3195546/

It makes sense that it is not the food’s pH that determines how it affects the pH of our bodies, since there are so many enzymes and reactions that take place. Also, our stomachs are very acidic, with a pH around 3, so not many foods would bring that down through their acid concentration, and lead to discomfort, since we’re already so acidic. Instead, what we eat may induce reaction within the body that lead to significantly acidic products.

Yet another way biochem makes my lab life easier! This week, in order to finally get a better understanding of my lab project, I decided to use PyMOL to look at the binding of biotin to avidin, which are used on my nanoparticle project! Avidin is a dimer protein which can bind four biotin molecules with a binding capacity of 10^-15M, which, for those of you that aren’t familiar with binding capacity, is REALLY strong. You can partially see why from my figure, where two of the biotin molecules, colored red, are shown in the binding pockets of avidin.

It is always stimulating when classes overlap in material covered. I found our last class on neurotransmitters to be interesting because earlier this week in my BioPsychology class we discussed ways to interfere with/manipulate neurotransmitter activity. Neurotransmitters are chemicals stored in vesicles at the end of each neuron. Once an electrical signal is propagated to the end of the neuron, the depolarization opens up these vesicles and neurotransmitters are released in order to bind to and fire the next neuron. The firing of these neurons are responsible for our emotions and reactions to situations i.e. fear, sadness, happiness. Sometimes these neuron circuits fire too frequently; sometimes they don’t fire enough.

As was discussed in class, amino acids are used as precursors for making neurotransmitters, with the help of enzymes. For instance: Phenylalanine (from your diet,) tyrosine and dopa are used to make dopamine, norepinephrine, and epinephrine. Tryptophan(from your diet) and 5-hydroxytryptophan are used to make serotonin.

For drug designers who make anti-depressants and other psychotropic medications, their major endeavor is finding efficient, effective ways to manipulate neurotransmitter activity with the desired effect, while minimizing side effects as much as possible. It turns out one way we can directly manipulate our own n.t. activity includes what kinds of proteins we eat, which might be heavy in ingredients such as phenylalanine and tryptophan.

Today, since we’re going to talk about Anfinsen’s experiments I thought I would talk about the interesting concept of renatured proteins.

I still think that this ability to renature after being denatured is a pretty amazing concept, almost paradoxical, simply because it’s  like reversing the clock! I have always been fascinated with concepts like time-turning or stopping time, mostly because I wish that there were more hours in the day (Don’t we all!) Also, I feel like this is a fairly rare phenomenon in the physical world because many of our everyday actions seem irreversible. The following are a few examples of what I mean by “irreversible”:

1.When you fry an egg – you’ve essentially and completely altered your egg. There is no way you can go back to the point where the egg was raw (or liquid-y!)

2. When you burn a piece of paper there is no way you can (on this timescale) retrieve that same piece of paper – it’s gone and lost to the world, existing now as bits of ash and ember.

Essentially we can see it’s because the disruption of noncovalent interactions (and disulfide bonds) is much less impactful than the disruption of covalent bonds – in the sense that we can disrupt noncovalent interactions in proteins to denature them, yet they can reform. However, once we disrupt the covalent linkages between proteins, that’s when we’ve dug ourselves into a hole that is hard for us to reverse the process.

Main point of this rather abstract article is this – science is very humbling and try not to . mess with your covalent bonds.