BIOC 223

Watching the movie in the review session reminded me of one of my favorite web comics, Hark! a Vagrant

It’s a little painful to watch the (admittedly dramatized) examples of casual sexism Franklin endures in the movie. Adding insult is the fact that Franklin didn’t receive recognition until after her death. In that spirit, I looked up some great women who contributed to scientific research. The link is a great read if you are in need of some inspiration or a pick-me-up.

http://www.smithsonianmag.com/science-nature/ten-historic-female-scientists-you-should-know-84028788/?all

Hi all!

I just wanted to shared with you a song that I wrote over the break. It’s called  “The Building Blocks of Life” and it intends to break down (pun partially intended) the different levels of protein structure and how the four main organic elemens, C, H, O and N are able to create such a diversity of structures that are conducive to life as we know it! Below is the link (mp3 is too big a file to share otherwise), and here are the the lyrics if  you wanted to follow along!! Apologies in advance for the poor recording – I don’t have any of my recording equipment with me at school..

https://soundcloud.com/audrey-amadea/the-building-blocks-of-life

The Building Blocks of Life

Let’s start out with some elements

C, H, O, and N

They differ in the number

of protons their core contains

Line ‘em up in a million ways

Like Legos upon the sand

Don’t need imagination

To admire your creation

X With four simple atoms you can see how life began!

Arrange these “letters” in such a way

To make what’s called a functional group

And these various “anagrams”

You’d be amazed at what they can do

A carboxylic acid and amino group

Just two examples of more:
One is acidic, one is basic

One giveths and one takeths

The protons in solution in a constant tug-of-war!

Amino acids have both of these

Both are linked to a central C

Amino acids are the building block

Of proteins that we need (to live)

Twenty kinds that are known to man

So that’s twenty different beads

If you string them all together

And vary up the order

You’ll make a polypeptide – what useful jewelry!

Let’s be clear for a moment

A polypeptide is not yet a protein

A protein must have structure and function

And all we’ve done is drawn up the blueprints

(primary structure, if you will)

We’ve got the order of amino acids

But that tell us nothing still….about

How the residue will interact

In its surrounding environment

Will it play nice with the other kids?

And with the water solvent!

Noncovalent interactions can certain atoms create

Van der waals, electrostatic, and the tendency to segregate

Due to hydrophobicity or lack thereof you see

All you need to keep in mind

is that like dissolve in like

And hydrogen bonding to add stability

Each amino has a backbone

That spells out N-C-C

Due to this special pattern

The backbone will fold accordingly

Alpha helix or beta sheet

Two very common forms

This folding is inherent

To the backbone that’s apparent

That’s why these secondary structures are very much the norm

Then we move up one level

Tertiary is where we sit

Due to side chains interactions

Twenty different sides we can pick!

All these side chains have properties

Like size and polarity

These quirks and small distinctions

make each “bead” quite unique and

that’s the explanation for the protein shapes we see!

One last thing before I go

And that’s to help you appreciate and know

How these subunits can come together in the end

To fraternize with other subunit friends

Multiple polypeptides can a single protein have

These peptides come together

To form a certain network

That’s the quaternary level and we’re almost at the end!

So this my friends is how proteins are conceived,

Atom by atom, piece by piece

The structural levels of a protein I confess

Simple and yet complex!

Glucosamine forms part of the extracellular matrix, and we mentioned briefly in class how some people take it to try and treat arthritis. In vitro studies have found that adding glucosamine decreased the levels of cytokines and interleukins while increasing transcription of genes associated with cartilage production. However, there has been much less data that supports the effects of glucosamine in vivo. Two European studies showed that taking glucosamine decreased knee joint-space narrowing over a period of three years; however, the difference compared to a control group was only about 1 mm. Additionally, other clinical studies have shown no significant difference between glucosamine and placebo treatments in treating pain. The bigger problem with using glucosamine as a treatment is that the liver filters out most of the glucosamine before it ever enters the blood stream or comes in contact with any joints.

While researching alpha-lactalbumin for my lab paper, I came across some really interesting news about it. For some background, alpha-lactalbumin is found in the breast milk of many animals. It is produced in the mammary gland and forms one part of the heterodimer, lactose synthase. Lactose synthase is an enzyme that joins galactose and glucose to form lactose. Furthermore, it has been found that alpha-lactalbumin is only present during lactation in healthy women. Recently, however, it has been found to be present in women with breast cancer. In 2010, Vincent Tuohy of the Cleveland Clinic’s Lerner Research Institute developed a vaccine that targets alpha-lactalbumin production in order to arrest the development of breast cancer tumors. They tested the vaccine on mice and were able to successfully prevent tumor formation and were also able to treat tumors that had already begun growing. This is super cool because this vaccine does not damage healthy breast tissue and is relatively painless for the patient! This would be very useful for women who are carriers of mutated BRCA1 and BRCA2 genes or for women over the age of 40, when a woman’s risk of developing breast cancer begins to increase. So far this vaccine has only been tested on mice, or that’s all I’ve been able to find on the internet about how far they’ve gone, but they had great results with the mice so I think it’s a vaccine worth keeping an eye on!

Wonderful Moment I thought I’d share to lead into a great Spring break…

https://www.youtube.com/watch?v=ZlfIVEy_YOA#t=70

Additional PBS report:

http://www.pbs.org/newshour/bb/evidence-of-cosmic-inflation-expands-understanding-of-universe-origins/

I realize this its a little late to be talking about proteins, but I was reading a lab paper which casually mentioned that the distinctive color of Siamese cats is dependent on a temperature sensitive form of albinism. Research has tied this phenotype to a single point mutation in a pigment gene called Tyrosinase. No one has studied how this changes the protein conformation, but I think it’s really interesting that the protein is so sensitive that a small temperature difference significantly changes the protein conformation.

Hello from ACS!! The conference started today and I thought I’d start posting some of the stuff I learned while it’s still fresh. We were at a medical science poster session today and were treated to an elaborate talk with a computational chemist working on modeling drug molecules and the systems they work with to better understand how structure relates to efficacy and how we can improve current drugs. One of the things he talked about was halogen bonds, which are apparently similar to hydrogen bonds in that they’re dipole-dipole type interactions (http://www.halogenbonding.eu/halogenbonding.php, I did some back ground before sharing this) caused by uneven electron distribution in halogen atoms. They’re even the reason the thyroid needs iodine to function, because one key hormone, thyroxine, in the thyroid relies on iodine to interact with an oxygen on another molecule (http://www.pnas.org/content/101/48/16789.long). He claims that materials chemists have been using halogen bonds for quite some time without many of us even being aware, but as you can see, they’re biologically useful too!

I’m currently procrastinating because I don’t feel like getting started on my to-do list, and I found this great blog post on chocolate chip cookies:

http://sweets.seriouseats.com/2013/12/the-food-lab-the-best-chocolate-chip-cookies.html

Kenji, the author of the post, is a foodie with a serious passion for researching the science behind cooking. This post is one of my personal favorites, as it takes a very in-depth look at the process of baking. I’ve heard the phrase “baking is like a science” thrown around before, but Kenji takes it to an extreme. In order to develop his ideal chocolate chip cookie recipe, he bakes over 1500 (!!) chocolate chip cookies to test the different variables. He also discusses many of the biochemical processes at play in cookie-formation, many of which relate directly to what we are studying in class. Here’s some of my takeaways from the article.

• Gluten develops when flour mixes with water, and is actually a network of interconnected proteins. The formation of this network in cookies helps the cookie spread, and also lightens the texture. This network can’t form in fats, which is why a higher amount of butter in a cookie recipe leads to a more compact, less cakey cookie.
• Browning reactions (aka the Maillard reactions, as previously discussed on this blog) lead to the color of the cookie. A larger amount of proteins in the dough lead a darker cookie.
• For the best cookies, allow the dough to rest before you bake. He suggests letting them sit overnight before baking. The rationale is similar to issues we face in biochem lab: many of the reactions taking place in the dough (protein interactions, acid-base chemistry, etc) occur gradually. Letting the dough sit allows more of the reactions to occur, leading to a more complex cookie.
• Order and technique matters! Changing around the order in which ingredients were added to the dough led to textural and visual differences. Same with the techniques used, i.e. whipping the butter vs. browning the butter. This reminds me a lot of lab, and the importance of writing a thorough methods section.
• White sugar is crystallized sucrose, and is mildly hygroscopic and relatively neutral in pH. Brown sugar is crystallized sucrose, with some glucose, fructose, and trace minerals. The addition of glucose and fructose makes brown sugar more likely to retain water, while the trace minerals provide additional flavor and slightly lower the pH of the sugar.

If you too are procrastinating, I highly recommend his blog. This article is a bit of a long read, but well-worth the time (and the comments are a goldmine of cooking advice as well!)

I would like to continue along the same vein as Audrey in terms of relating basic biochemistry to our own lives- with perhaps a bit of social psychology incorporated.

Bio-chem component: Proteins with different primary structures, giving way to different combinations of the amino acids, which range in charge, size etc result in proteins which interact differently with their environment.  The result is that, in general, a protein in the cell will fold up into a quite specific, functional shape called its native conformation that is favored energetically over the disorderly soup of molecules of other shapes that cannot accomplish the biological function of the natively folded protein.

Psych component: I would like to draw a kind of wonky connection between what we were talking about last class, concerning carbohydrates, and how they interact with their environment in the same way proteins due, based on charge/polar interactions (or in terms of the dieletric constant, as another way to think about it,) and a concept called heritability- something I have come across in my Psych classes.  Heritability is often thought to be a general concept, equally applicable to any part of the world. However, it is actually population-based, meaning the significance of genetics varies based on location: the less the diversity of socio-economic/educational background in a particular community, the more significant the genetic variability whereas a community with more socio-econmic/ educational diversity has less significance in terms of genetic variability. So the environment in which we live is very important, the people we surround ourselves with is very important!

Anyway- here’s my bit of a stretch comparison: Just as we are very much influenced by the environment in which we grow up in, particularly the interactions we have with family members, friends, teachers etc, molecules too (carbs and proteins) are influenced by their environments. If we fit well in our environments, we begin to shape ourselves as cohesive members of those environments, soluble in the culture of the community, performing a certain purpose for that community. However, if we do not fit well within the community, we might become insoluble, isolated, unable to perform a specific function as part of the community. As young people grow up, through trial and error, they go through a messy process of folding and unfolding, until they reach the right shape. This goes along the lines of the ugly duckling story if I remember correctly. And some time around High School, college or later, we find our native conformations, the state in which we feel we can authentically be ourselves. Of course we will face many different kinds of environments going forward, perhaps more diverse in nature than a cell will ever come across- for there is not much leeway in deviating from physiological (pH 7) conditions, but as we face these environments, we too have chaperones, aka our own self understanding, friendships, and family!

One common theme of BIOC223 and organic chemistry as well seems to be that the drastically, dramatically different differences that are relevant on a human scale can be attributed to the different ways elements can bond to each other. Elemental composition is almost meaningless in the organic chemistry and biochemical world – what gives us insight about function is the 3D structure, the network, and how these elements are bonded or interacting with one another. I think this is a pretty rad concept because it forces us to constantly rethink – it’s not just the building blocks that matter, its how the building blocks relate to each other! In this whole shpiel, I feel like I could have inserted a “parts are greater than the whole” comment somewhere.

Sticking with the week’s theme of carbohydrates, and also drawing from what we learned in today’s lecture, I wanted to show an example of what I mean by the relationship between the building blocks. Enter stage right: the difference between cellulose and starch. Both consist of glucose polymers, so one might initially expect them to have similar properties. However, because starch has alpha (1,4) glycosidic bonds and cellulose has beta (1,4) glycosidic bonds, that completely changes the geometry of the sugar polymers. Because of their different spatial arrangements, human enzymes cannot process cellulose (its linear shape won’t fit into the active site of the enzymes), though we can process starch.

So why is this relevant to humans?  Certainly this is an interesting topic,  because cellulose and starch crop up all over our favorite foods! Fruits and vegetables are often great sources of cellulose, while breads and potatoes are great sources of starch. Perhaps in a “perfect” world (for all those bread-lovers), we could swap the bonding pattern of starch and cellulose. Wouldn’t it be crazy to think might that pizza dough might have more health benefits than celery?