DIARY OF A BIOCHEM MAJOR

Well I’m finally settled down at Case and starting my REU! I’m still waiting on my own project but it should be dealing siRNA and their role in preventing/stopping cancer, so I’m pretty excited to say the least! Once I know more specifics, I’ll be sure to bore/entertain you all with a better write up.

Today’s molecule is brought to you by sleep! Without it, how could have all those awesome dreams that make reality seem oh so boring? Be warned though, taking too much of this molecule and you could end up dreaming while you are awake (aka hallucinations). While that might seem like fun, the permanent sleeping condition know as “dying” can result which will quickly put an end to things.

Ambien, also known as Zolpidem, is typically used to treat insomia. Its much stronger than the OTC varieties, and due to its potential to cause addiction, is only available with a prescription. Once Ambien gets into your blood, it heads straight for the brain where it interacts with GABA receptors. Now GABA is a neurotransmitter that actually inhibits the nervous system (aka GABA=feeling sleepy). What happens is that Ambien comes in binds to the GABA receptor (more specifically GABA A receptor) where it acts as an agonist. An agonist is something that up regulates a protein/enzyme so basically Ambien causes the GABA receptor to become more sensitive to GABA.

I’m feeling kinda sleepy now, brb allowing GABA to work its magic. 

Ah Hawaii, how I love your beaches and constant sunshine. Beats the heck out of Atlanta, plus its a nice way of unwinding after finals at Tech. Sorry if I haven’t posted that much, between grading the finals in orgo and trying to survive my own finals, my tumblr-life took quite the hit.

Is it me or do all the cool drugs have some weird structures? Seriously, everything that I’ve seen seems to indicate the more rings the better! Heck, toss in some bicyclic rings and you’re golden! (Yo dog I heard you like rings so we put rings in your rings…)

Hydrocodone is one of the active ingredients in Vicodin, a powerful pain killer. Its commonly prescribed after getting your wisdom teeth taken out, and let me just say it works extremely well. The first day or so was nothing but a blissful haze, especially considering I just had four teeth yanked out my mouth. Apparently I tried to write something down but my hand writing/thoughts were so out of whack I still have no idea what I was trying to say…

Once hydrocodone gets into your brain, it heads straight to the opioid receptors (which affect mood along with the sensation of pain and also have a more sinister function of leading to dependence). However, its actually processed by the liver to a more potent version called hydromorphone by a family of enzymes called cytochrome 450. Fun fact, the 450 part comes from the fact that the heme group in the enzymes absorbs light at 450 nm.

Who would have thought that the end of the semester would be so hectic…gah…

Anyways, if you have ever gone to the dentist to get a cavity removed, you’ve probably had this injected into your mouth. Now dentists love to tell lies, such as “Oh this won’t hurt” when they jab the syringe into your gums. Its basically along the same lines as “Oh the reason why you are bleeding is because you are not flossing enough” as if jabbing my gums with sharp pointy metal picks wasn’t the reason.

Novocaine is one of the most common pain killing medicines are the market today. It’s used by dentists due to the fact that its effects are typically localized to a small area (though that “small area” can be as big as your face, having my entire face going numb was an interesting experience to say the least). It’s also non-addictive as well which makes it stand out among its peers.

Novocaine’s mechanism of action is pretty simple. Throughout our body, we have nerves that give us the feeling of touch (and pain). In order to communicate with the rest of the body/brain, the nerves use an action potential (basically a change in voltage). Novocaine works by depolarizing the nerves, which disrupts their ability to transmit a signal. This is why your face can occasionally feel numb after getting injected with Novocaine as the nerves are prevented from working at all. Luckily the effect wears off in an hour or two.

Today’s molecule is pretty crazy (not because of its structure which is mind numbingly complex) but because it has the potential to stop an epidemic.

Raltegravir, also known as Isentress, was discovered by Merck a few years ago and is an extremely powerful HIV drug. It was approved by the FDA in 2007 has been a huge hit ever since. In fact, it was the first integrase inhibitor on the market and has spurred research into that area in order to create a whole new class of integrase inhibitors. 

Now HIV is a type of retrovirus, meaning that instead of carrying DNA, it instead contains RNA. Using some viral enzymes, the RNA from the virus is converted in cDNA which is then integrated into the host DNA. Following the insertion, the cell starts to make copies virus which then begin to bud off. HIV is so devastating because it targets the immune system, specifically the white blood cells. HIV doesn’t actually kill anyone, it just comprises the immune system to the point that it can’t fight off normally benign infections.

Raltegravir comes to the rescue by blocking the insertion of the viral cDNA into the host DNA. The virus typically carries an enzyme called integrase which it uses to insert the cDNA. This point is a critical fork in the road for the host cell. If it gets infected, there is no turning back as it now contains the viral genome. However, if integrase is somehow blocked, it would like if the cell never got infected in the first place.

Integrase contains a magnesium ion in its active site which it uses to help speed up the integration. Raltegravir works by binding to the magnesium ion which effectively prevents the enzyme from binding the host DNA and therefore preventing the viral cDNA from being taken up.

Now HIV mutates at an extremely fast rate which is why patients with HIV typically take a mix of antiretroviral drugs in order to combat all the potential mutations. The high mutation rate is also why its hard to find a “catch all” cure since what might work with one person could potentially not work with another.

Drew this during lecture today. I now know what my thesis will be about!

“The extraction and insertion of fried porcine DNA into autotrophs for the purpose of growing delicious bacon trees.” 

And I’m back! Finally got my new laptop set up after about a week of have little to no internet access (first world problems at their best).

Today’s molecule is inside you right now…lurking…just waiting to strike! Luckily its actually important (slash that, necessary) for you to live. Its involved in some the biggest, most important pathways in the body and is generally responsible for keeping you alive.

Glucose is actually a pretty simple molecule. Its either found in its linear form (as pictured above) or as a six member ring. In the body its nearly always in the cyclic form as that’s the form the body’s enzymes use. Once food enters the body, its changed into simpler molecules in a series of steps. Proteins as typically broken down into their amino acids by enzymes called proteases. Sugars and lipids (such as your standard fatty lumps) are broken down via separate pathways which typically end in glucose.

The body needs glucose for one specific reason, and that’s to get energy. As you might already know, ATP is used to drive the cell’s machinery and is basically responsible for keeping the cell alive. The cell can harness the energy found in glucose by feeding the glucose into a pathway called the glycolysis cycle. In this pathway, one glucose is broken down to form two molecules of pyruvate (as seen below):

Two ATP molecules are created during this process, but the real energy comes from the next pathway. Pyruvate can be feed into another cycle called the citric acid cycle (also known as the Krebs cycle). During this pathway, pryuvate is converted into CO2 while the energy is captured by various electron carriers. These electron carriers are then feed into the electron transport chain where nearly 30 ATP molecules are created. Overall, the cell can create around 36 ATP from one single molecule of glucose.

And that’s just a brief overview of the different pathways. Each cycle has tons of different enzymes and mechanisms. Now my Biochemistry II class has basically been about these pathways so far, and at this point the last thing I want to see is another molecule of glucose. So I raise my glass to glucose, the one molecule that keeps me alive while I try bash my head into my biochem book learning about it. Cheers.

The new national program to graduate more engineers started its kick off at Tech today (but everyone knows biochemists are better anyway :P)

Its been way too long since my last featured molecule and today I have a special one for you!

Well by special, I mean its ability to kill you without you really noticing. This little guy loves to get into your body and screw around with all sorts of processes that have this somewhat important purpose of keeping you alive.

Hydrogen sulfide is actually quite simple. With only two hydrogens connected to a sulfur, its hard to get an even simpler molecule (minus those pesky gases). Outside the realm of biochemistry, hydrogen sulfide is used for a lot of different industrial purposes ranging from the production of heavy water (used in nuclear reactors) to forming precursors for various drugs (yay!).

However once it gets inside of your cells, everything basically breaks down.  Our cells survive through a process called cellular respiration. This process takes broken down food molecules and uses them to synthesize ATP which is energy “currency” of the cell. Cytochromes play a very important role as they help transport electrons to and from molecules and hydrogen sulfide, being the jerk that it is, comes in and deactivates it by attacking the metal ion in the center. If these proteins get knocked out, the cell basically starves to death as it can no longer produce the energy that it needs to, you know, keep you from dying.

Whats even more awesome is that hydrogen sulfide can deactivate our sense of smell. So initially you might notice a faint rotten egg smell, but it will soon go away as the molecule attacks olfactory nerves. You’ll only notice its effects when all of sudden you faint.

Ironically our bodies actually use the compound as a signalling molecule. Since it is sort-of (only slightly of course, I mean who cares if your cells starve to death?) poisonous, our bodies have a special enzyme to it down. However it can only handle so much before its overwhelmed and that’s when all the fun things happen.