BIOC 223

I was discussing the pros and cons of getting a tattoo with a friend the other night, and I started to wonder what exactly goes into getting a tattoo. A quick internet search told me some of the basic ideas behind tattooing, which I thought I would share! Turns out, many of the vibrant colors found in tattoo ink are actually derived from heavy metals, something I never even thought of. Green from copper, red from iron, blue from cobalt…it’s pretty amazing (and a little alarming). It seems the heavy metal pigments are pretty stable and are therefore considered safe for use in the body, but our recent lectures on membranes have me wondering if any serious scientific studies have been performed on this topic. After all, our skin is an organ, so it’s pretty interesting wondering what the effect of forcing heavy metals into the skin has on the membrane chemistry.

Would you ever get a tattoo?

Not directly related to biochemistry, but it’s definitely worth thinking about how van der Waals interactions may affect these Newtonian fluids.

http://www.npr.org/blogs/thesalt/2014/04/29/306911004/whats-the-secret-to-pouring-ketchup-know-your-physics

After all the computational modeling that we learned about this week, I was curious which other ways chemists use modeling. One important development is modeling the interactions of complex chemical systems, and Levitt and Warshel were awarded the Nobel prize in chemistry in 2013 for developing a new way of modeling these interactions. Their modeling system integrates quantum mechanical analysis of key atoms in the reaction (which is computationally intensive) and classical mechanical analysis of the rest of the atoms (which is much easier to compute). This method allows researchers to analyze molecules such as enzymes much more efficiently and in more depth because only some parts of the protein are heavily involved in the protein’s function.

With all the snow this week, I’ve been thinking about how hydrogen bonding effects the visual properties of snow. For example, snowflakes are six sided because as water freezes it forms six membered rings. This is also why snowflakes are symmetrical because a snowflake grows as water molecules bind to the original, symmetrical ring. Snowflake shapes vary because of changes in atmospheric conditions that effect water binding during the snowflake’s growth.

The other week as we were discussing the biochemical mechanisms of poison ivy and how that works got me thinking about other unpleasant encounters in nature, namely jellyfish stings! How does a poison work to a) bring about pain and b) in the most extreme cases, bring about death? Is the pain psychological or physiological? and perhaps most practically, how does the biochemical structure inform the biological mechanism, so that we might figure out a way to treat these painful and poisonous jellyfish stings?

When searching, I didn’t get as much of an answer for part a) but I found an awesome article that explains b) perfectly – very, very satisfying

Angel Yanagihara and colleagues at University of Hawaii and abroad have been trying to figure out the physiological mechanism of jellyfish stings .  Apparently the blow of a jellyfish sting is due to these porin proteins which can rupture blood cells and release extreme amounts of potassium in the bloodstream – which leads to rapidly increasing heart rate and ultimately death. An very fascinating and thorough article on a new treatment for jellyfish stings can be found below!

http://blogs.scientificamerican.com/science-sushi/2012/12/12/dont-pee-on-it-zinc-emerges-as-new-jellyfish-sting-treatment/

Preparing for my midterm this week and also working on my final project I’ve been fascinated by how much biochemical interactions both covalent and non covalent are at the heart of life and how disease can arise when bacteria and virus take advantage of the same. Some viruses infect cells by first binding to receptors on cells which they recognize based the interactions they form. I was pleased to learn in our exam though that preventing some of these interactions, covalent in this case, can have life saving effects like preventing HIV DNA replication in AIDS patients!

In honor of our future work on membrane proteins, I thought I’d share a little bit about cystic fibrosis, an autosomal recessive disease that affects 30,000 Americans. Most people are diagnosed by age 2 and life expectancy is typically in the 40s. It’s actually the most common autosomal recessive disease for Caucasians, although it’s prevalent in all races, and thousands of people are carriers. Cystic fibrosis is caused by mutations in chloride ion channels, part of the ATP-binding cassette (ABC) transporters used by cells to regulate water levels inside and outside the cell. Because water can’t be regulated by the cells anymore, thick mucus builds up, crushing cilia that line the lungs, pancreas, reproductive tract, and many other surfaces. This mucus is a great environment for bacteria to grow, and cystic fibrosis patients are often infected by pathogens like P. aeruginosa, making the quality of life even worse than it already is, as the mucus makes it hard for patients to breathe and often makes both men and women infertile.

In Orgo II the other day, we discussed a super interesting biochemical application of beta-lactams moieties. Lactams are cyclic amides (also known as lactone amides) that are most often found as either six-membered rings, called delta-lactams, 5-membered rings, called gamma-lactams, or four-membered rings, called beta-lactams. Here’s a good representation of these from Wikipedia:

The beta-lactams, or four-membered lactams, are extremely reactive since four-membered rings are very sterically unfavorable. Because of this inherent reactivity, these beta-lactams can be inserted into molecules to add a reactive site to the molecule. Commonly, these beta-lactams are used in antibiotics, such as penicillin, shown below.

The beta-lactam in penicillin reacts with the hydroxyl groups of in or near the active site of bacterial enzymes. Specifically, it reacts with the bacterial enzymes, called transpeptidases, that cross link the bacterial cell wall together (NAM-NAG-, etc, just like we reviewed before!). Shown below is a representation of penicillin reacting and blocking the active site of one of these transpeptidase membrane building enzymes in bacteria by acylating the enzyme.

The reactivity of these beta-lactam moieties allow the antibiotic to bind to the transpeptidase membrane building enzymes, also known as penicillin binding proteins, in the bacteria. This therefore impairs their ability to correctly cross link the membrane and the membrane falls apart. Furthermore, resistance to these beta-lactam agents occurs when a bacterium can produce a penicillin binding enzyme that has an active site with a conformational change that does not allow beta-lactam binding to occur. Bacteria can also produce beta-lactamases that bind with the penicillin before it is able to bind with the penicillin binding proteins at all! Cool, huh?