06/19/2022
A musing (which may or may not be amusing):
I've frequently been bothered in discussions of enzymes and basic biochemistry by the rather flippant way that many instructors choose to define a kinase as "something that puts a phosphate on" and a phosphatase as "something that takes a phosphate off." It's oversimplified and also presumes an agreed-upon perspective for which molecule(s) would be donating or receiving said phosphates.
This is problematic, because when a group is "put onto" a molecule in a chemical reaction, that group typically came from some other molecule that had it "taken off." One of the first things you learn about in basic chemistry is the principle that the involved matter is conserved and that *everything has to come from somewhere*. Thus, a kinase only "puts a phosphate on" from the perspective of one of the substrates, whereas is acts as a (colloquial) phosphatase from the perspective of the substrate that acts as the phosphate donor. In other words, both a kinase and a phosphatase will tend to ass a phosphate and remove one, with the distinction being a rather arbitrary one about which substrate(s) we choose to adopt as the protagonist of that particular chemical reaction.
Even if we can start off all agreeing that a particular substrate and its descendants will be the focus for what is adding or losing a group, the definition *still* can break down. Take glycolysis, for example:
The first phosphorylation reaction -- and the first overall in the pathway -- is the hexokinase reaction. It converts plain old glucose to glucose-6-phosphate (G-6-P, where a phosphate group is attached to the sixth carbon). It *added* a phosphate to glucose, so it's a *kinase*. Simple enough, right?
So in the glycolytic pathway, the kinases should be the enzymes that add a phosphate to a substrate as we move down that pathway. For each reaction, we are choosing to focus on the product that remains in the pathway (not the product that just floats away to do something else, such as ADP from that hexokinase reaction; we just don't care about it). So step one converts glucose to glucose-6-phosphate. Step two converts that to fructose-6-phosphate (an isomerase reaction). Step three adds another phosphate to the molecule to create fructose-1,6-diphosphate/bisphosphate (via the phosphofructoKINASE enzyme in a powerfully rate-limiting step), and so on.
Seems fine so far, yes? When the next downstream product of that original glucose -- whatever is staying in the pathway to move to the *next* reaction and continue glycolysis -- gets a phosphate, it's given that by a kinase enzyme.
Except it breaks down. The reaction that creates pyruvate at the end (what is often taught as the "final product" of glycolysis, though I don't entirely agree with this) does so by removing a phosphate from something called PEP, or phosphoenolpyruvate. That enzyme is: PYRUVATE KINASE. It removes that phosphate to replenish an ATP molecule (it actually does this twice, since it's operating on both legs of the pathway which split several steps before this).
So suddenly, we have a kinase that is *taking a phosphate off* instead. This is why simply defining kinases and phosphorylases by whether they add or remove a phosphate group is a mistaken approach. That kinase was still adding a phosphate to something; it was just doing it to the ATP instead of to the glycolysis intermediate we would expect.
Okay. There's my rant. I've attached an image of glycolysis so you can see what I'm talking about (hopefully it'll be readable for you). Just needed to get that out of my system. This isn't something that confuses me, but it definitely does confuse students who are first learning these concepts and being given mindless memorization approaches to the topics instead of more thorough explanations about what's going on. Simplicity is not always the friend of the beginner.
Here's one of about a million different sites that explain the process (with some mention of the fact that the pyruvate kinase enzyme is named for the reverse reaction in this case):
https://courses.lumenlearning.com/wm-biology1/chapter/reading-glycolysis-2/
