“Old School” Biochemistry Still There
I sometimes jokingly refer to the study of metabolic pathways as “old school” biochemistry, from the era of Hans Krebs, Melvin Calvin, and Konrad Bloch. More often than not, when you hear “biochemistry” uttered by a molecular or cellular biologist these days, they’re referring to measurements of how much proteins stick to each other, not studies of the biosynthesis of a sugar or other molecule. Really, it’s kind of a divide between biologists and chemists. When organic chemists talk about biochemistry, they still pretty much have old school biochemistry in mind, whereas biologists don’t seem to think of that too often.
Still, “old school” biochemistry is still kicking, and its study still generates great life-saving cures, like the Statins, which inhibit HMG-CoA reductase. Metabolic diseases are still some of the highest causes of death in the world, so the study of all these pathways by med students is still of great use. As an aside, Harvard, of all places, doesn’t really seem to have a biochemistry course (the closest is the “Chemistry 27″ course on topics in bio-organic chemistry). Guess they figure the students can always look it up and learn it later if they need it.
One thing I really like about medicines targeting metabolic pathways is that sometimes (and this is just sometimes), there’s something just refreshingly intuitive about the approach to those diseases. Too much cholesterol? You can keep it from being made (e.g. via statins) or you can get rid of the excess (via bile acid sequestrants, like cholestyramine). The latter method is quite interesting; though statins get all the press, bile acid sequestrants apparently also work quite well (but they’re not as easy to take as popping a statin pill). These are essentially resins that a patient swallows, which then absorb bile in the intestine. Thing is, bile is made from cholesterol, so if you remove a lot of bile, the body tries to make more from the cholesterol, thus draining the amount of cholesterol in the system. Pretty harmless.
Another really interesting application of “old school” biochemistry in medicine cropped up in the science news recently, with a 25-year study that was published in the NEJM today. See, the urea cycle processes the nitrogen in the body, breaking down proteins and removing the nitrogen parts as urea, which goes into urine. Some people, however, are born with defects in the urea cycle, which can lead to having too much nitrogen in the blood in the form of ammonia. Ever smelled ammonia? Yeah, don’t want too much of that in the blood. People fall into comas because of it.
So, what to do? How about supercharging another pathway in the body that gets rid of nitrogen atoms? One way is to hike up the synthesis of hippuric acid, which is the form in which the body gets rid of benzoic acid. Hippuric acid is just benzoic acid with a glycine molecule attached; glycine is an amino acid with one nitrogen atom in it. So, just add a bunch of benzoic acid (or sodium benzoate, which is equiavalent), and when the body tries to get rid of that, glycine will hitch a ride! It works quite well, according to the study. The other way to help is to form phenylacetylglutamine, which is phenylacetic acid stuck to a glutamine molecule (which is another amino acid). Glutamine has 2 nitrogen atoms per molecule. Even better! So just hike up the phenylacetic acid in the body, and in the race to get rid of that excess, the body will get rid of a bunch of glutamine with it. Put the two ways together, and you get a great way to reduce the ammonia levels in the blood. Pretty neat, I say!
