Sunday, November 23, 2008

Stereochemistry

I like to be reminded from time to time that I have only just scratched the surface. It helps put things in perspective, and I find the realization of depth to be an exciting thing. It is a major part of what I enjoy about this job, that each day holds the opportunity to learn something new, and that each call holds the potential to reorient my view upon everything else. Lately however, I’ve found these lessons coming from a different source. My lectures and laboratory sessions at school are slowly transforming from dull academia into practical application, and I’ve relished a few opportunities to take new depth with me from the classroom to the job.

Organic Chemistry is a beautiful science. It is famously difficult, the “weed out” class for pre-medical students everywhere, and this semester has taught me exactly why. It is a science that requires a particular kind of continuous knowledge, applied together in the assembly of functional chemical compounds. To understand organic chemistry is to understand a particular set of tools that are used to create highly specific, exotic chemicals out of cheap and common starting materials. The process is often arduous, but the fruits of this labor are the fuels and medicines that shape our lives today. There is good reason people have put such work into developing our understanding of this science.

I have been lucky to associate some of this science with my work on the road. These studies have taught me about the importance of detail. To know a thing is to understand how and why it behaves the way it does, to understand it from every angle. This kind of scientific intimacy brings to light exactly how delicate our tools are, and how specifically they are engineered.


Above is a drawing of the chemical structure of epinephrine. These specific orientations of carbon, oxygen, nitrogen, and hydrogen might seem like unnecessary detail, but this structure holds within itself a real power. My studies have taught me how to pull that flat drawing out into three dimensional space, to give life to that compound and make it real.

That drawing above isn’t just epinephrine. It is more specific than that. The forward orientation of the hydroxyl group (the “OH” near the top) is particular to this form of the compound, and is specifically named (R)-(-)-Epineprhine, or Levo-rotary Epinephrine. This is to differentiate this particular orientation from its isomeric sister: (L)-(+)-Epinephrine (Dextro-rotary Epinephrine) in which the “OH” points in the opposite direction. See, epinephrine has a point of rotation (a point of “chirality”) that enables the molecule to exist with the same chemical formula, but slightly different three-dimensional orientations of the components. The phenomenon is called stereoisomerism, and it is more than just academics. A small change in the three dimensional shape of Epinephrine is what differentiates the biologically active from the not biologically active. Levo-rotary Epinephrine is the vaso-constricting, heart-stimulating, bronchi-dilating drug we are familiar with. Dextro-rotary Epinephrine, however, is essentially inactive. Our bodies, in all their wisdom, produce an enantiomerically-pure product: the levo-rotary epinephrine only.

Stereoisomers such as Epinphrine can be separated into their individual isomers (“enantomers,” in this case), or can be combined together into a mixture. When enantomers are combined together in equal proportions, Organic Chemistry calls the mixture a “racemic” mixture. When we give patients the drug we call “Racemic Epinephrine,” we are actually giving a combination of the active form of Epinephrine mixed with an inactive form of the same chemical compound. This technique has a blunting effect on the potency of the drug, which is the desired effect. I was surprised to learn that the technique we use at my service to perform this treatment is slightly different. We don’t technically administer “racemic” epinephrine because we don’t have dextro-rotary Epinephrine in our drug bags. Instead, we take regular levo-rotary Epinephrine and mix it with saline, achieving the same blunting effect.

The same holds true for our diabetic patients to whom we administer Dextrose. I have been asked in the past why we give dextrose to patients who are hypoglycemic. Organic and stereo chemistry provides the answer. In fact, dextrose IS glucose, just the dextro-rotary isomer of it. (Dextro-rotary + Glucose = Dextrose) The chemical compound is oriented in a specific way, like epinephrine, and it is only this orientation that is synthesized by the body to create energy. It is by convention that we call glucose created outside of the body “dextrose,” and that created inside the body “glucose.” They are both the same thing.

It is all scientific detail. Esoteric, to be sure, but the depth is there for anyone who is willing to look. For a paramedic and pre-medical student such as myself, I find the incredible complexity of these subjects fascinating. To learn about epinephrine and dextrose in this way makes me wonder about everything else we do. There are layers and layers of understanding underneath each of our drugs, underneath our procedures, policies, and practice. We do what we do out of little but faith that there exists science and understanding to provide a foundation for these treatments. We accept our protocols wholesale because we have to, as they are the assimilation of greater minds with greater perspective. To scratch the surface of this knowledge, as I have done in class, does little more than add a sense of humility and wonder for that which I do not yet understand, and to provide a motivation to move forward and learn more.

In the future, I have bigger plans for this surface than a mere scratch.

9 comments:

Anonymous said...

If you don't use the book Organic Chemistry as a 2nd Language, start...

Chris said...

Ugghh - *organic* chemistry? What are you thinking?

OK, I'm getting fed up of chemistry in general now, but inorganic is so much better!

Chris

(4th and final year chemistry degree student!)

Anonymous said...

That bit about the dextrose is fascinating. I NEVER thought I'd want to touch organic chemistry with a ten foot pole and yet what you wrote is so interesting. Thanks for sharing!

es said...

well written and extremely interesting...thx for sharing

zac said...

Cool stuff, man. I loved ochem back in college... then again I was a biochem major :-)

Great bit about the dextrose, by the way.

Kate said...

That's funny that you mention how our bodies react to racemates of different compounds. When I learned that, I too was awed the way that something seemingly unimportant could matter so much. Pretty cool about the dextrose-- I never knew that.

Anonymous said...

*clap* *clap* *clap* The "paramedicine" industry is always going to remain "cook book chemistry" unless the NREMT is crippled and states are free to license paramedics and unions are given more bargaining power. It is interesting that Seattle has a 3,500 hour paramedic course that has a 3+ year waiting list. Conversely, some states push firefighters through a 3 month class to boot out an existing service. To clear the point for anyone that is confused so far, although the job is a 'calling' for some; for many, it will remain a manual labor job with a fancy title. As you posted earlier, some 'ER docs' just push the paramedic aside; with, maybe, a "good job". Maybe if the classes WERE 3,500 hours WITH a BS degree that included the first organic lecture, there would be more "job retention" and "employer appreciation" because diligent paramedics could easily finish coursework needed to elevate themselves to a much higher pay grade/ social status. Working paramedics need to recognize that the NREMT stands for 'big business' and not for the individual paramedic.....yet so many still pay homage.

Rachel said...

Just googled "racemic epinephrine chemical compound" to ask the same question you answer in your blog (whats the connection between racemic mixtures in o-chem and racemic epi?). Pleasantly surprised to find a blogger in exactly the same boat as I. I'm a brand new medic, currently studying for the MCAT. Best of luck to you in your studies!

Rachel said...

I just googled "racemic epinephrine chemical compound" looking specifically for the answer to a question you answer in your blog (what's the connection between racemic mixtures in o-chem and racemic epinephrine that I nebulize?). I was pleasantly surprised to find the blog of someone in exactly the same boat as I. I'm a brand new medic as well, currently studying for the MCAT. Best of luck in your studies!