Tuesday, April 28, 2009

Enzyme Kinetics

I've taken two biochemistry courses now, structural biochem and metabolic biochem. I guess this is a pretty standard undergrad curriculum. Both dealt with enzyme kinetics fairly extensively, and I realized today, sitting in class and going over bi bi multi-substrate mechanisms--ping pong and ordered sequential--that both classes took a totally different approach in allowing us to think about enzyme kinetics.

In structural biochem took an approach where we did Michaelis-Menton, inhibition, etc. but it was always in a "how can we change this interaction in the active site with the substrate to affect catalysis". It was pretty concrete to me, because you can mess with concrete, chemical interactions, like a hydrogen bonding interaction between residues, or some residue that kinks the protein out of alignment conformationally. Km and kcat had a directly linked cause--and that cause was intermolecular interactions.

In metabolic, it's sort of at this gross scale of when the substrate binds and when the substrate comes off. It's taking a step back from structure, and thinking about timing and mechanism at a larger scale. It's no longer this glutamate residue--it's just substrate A binds before substrate B. The mathematics feels so abstract, because I feel like I can't really picture in my head the fact that the blobular enzyme is undergoing small scale intermolecular interactions with the blobular substrate. It's just line drawings; it's schematics. I like it ok, and it's certainly a powerful approach. But what draws me to chemistry is structure, reactivity, and function. It's this viceral visual way of thinking about molecules coming together in space. And that's kind of lacking for me in Lineweaver-Burke plot after Lineweaver-Burke plot.

Incidentally, in reading the enzyme kinetics page on Wikipedia, I found it ammusing that "bi bi ping pong" was a totally technical term, and not a Ron-ism. Ron throws in conventional technical terms (which are, to be fair, often goofy sounding) with his own enzyme kinetics lingo, so sometimes hard to tell what is a general term that the biochemical community uses, and what terms are unique to him and his research. For example, he studies an enzyme that never lets go of its substrate, and so he likes to call those enzymes "Promethian enzymes". If you recall, Promethius in Greek mythology stole fire from Zeus, and to be punished, he had to be chained to a rock for the rest of his eternity while eagles ate out his liver. Then he would re-grow a liver and the cycle would repeat. So I guess that is an apt analogy.

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