The Enzyme is NOT the Protein

In my previous post I emphasized that the map is not the territory. I took String Theory off the shelf, dusted it off a little, and then mercilessly beat it up for no good reason. That was all well and good, but I want to address a point about biology that I think we sometimes loose site of.

The enzyme is not the protein. More precisely, the enzymatic activity is not the protein. Really said most completely, the function is not the protein.

Really, I am attacking a map. It's a map many have seen. It looks something like this. Or even like this.

As biologists, we often want to identify a protein's function. We're sort of obsessed with it, I guess. If a protein is necessary to survive, presumably it does something in the cell that allows life to happen. Maybe it helps break down bad stuff, or build up good stuff. Maybe it replicates DNA. Maybe it guards against invaders somehow. Perhaps it's a messenger of some kind, 'transducing' signals through the cytoplasmic ether.

We're helped along by the fact that a lot of genes really do seem to have a particular task to which they are assigned. Hexokinase has a very specific enzymatic reaction that it appears to be dedicated to catalyzing. It lives for the service of catalysis. Our very understanding of genes is driven largely by the observation of mendelian inheritance of genes that break these rigidly defined and clearly necessary functions. Animals with defects in these sorts of genes often suffer most obviously from some metabolic dysfunction, and we assign the gene to the metabolic disfunction.

Now that we have moved past simple metabolism to much more murky phenotypes, we seem to still be tied to the idea of proteins as acting to fulfill a certain function. It's as though they are machines designed to act as some cog that a watchmaker planned to use. Some examples: p53 protects against tumors. It's a tumor suppressor. Hif is a hypoxia sensor. VEGF is an angiogenesis factor.

Why can't these proteins have hobbies? Let's remember that evolution pressures a cell to survive, not to be elegant. In as much as survival is elegant, I guess that gets the cell there. But in the end the thing we're talking about is the most complicated gamish of protein you could think of, and it will do just about anything to get by. Whose to say that VEGF, in its off hours, doesn't swing by the glycolytic cycle for a little regulatory interlude. Perhaps Hif, during lunch hours, cruises by the spliceosome for a little slice and dice. Even the 'housekeeping gene' and paragon enzyme GAPDH appears to spend lazy sundays in the nucleus, a horrifying prediction for the one protein one function minded.

Let us remember that's what really happens in the cell is a very very complicated mess of reactions. Once a day in some cell in the human body I'd guess that every possible protein interaction pairing can and does occur. There's no reason that the cell hasn't evolved to use some of those strange pairings to give it a little more juice towards the end of its endless quest for self replication.


Which is all just to say that a protein doesn't need an easy to pin down function to be very important for the cell. Nor does a transcript with a well defined function necessarily not have other very important roles.


Here is the question we should be most concerned with. In all the cartographic glory of drawing out these maps, have we missed something essential? I've argued above that we've probably missed the fact that some proteins act in different places, and again missed that some places might occasionally be occupied by different proteins. I would argue that this is more than a frivolous attack, it explains why our experiments are so difficult to replicate and real advances are only rarely driven by deduction alone. We've only just scratched the surface of the combinatorial possibilities.