Hexokinase vs Glucokinase

In our conversation about glycolysis, we mentioned hexokinase and glucokinase. While they do the same thing, it warrants looking at what exactly the difference is between them and why.

They both have the job of phosphorylating glucose to make glucose-6-phosphate, which is a member of the glycolysis, glycogensis/glycogenolysis and the HMP shunt pathway. Kind of an important first step then, right?

The easiest difference is location. Hexokinase is in pretty much of all of our tissues except for the liver and beta cells of the pancreas. So, obviously, glucoskinase is present in the liver and the beta cells of the pancreas but not the rest of the body.

The reason for this is that the have different feedback mechanisms. Insulin, which is released in times of high blood sugar, does not effect hexokinase but it does induce glucokinase. That will make it more likely that we are storing our excess glucose in the liver and not in other tissues. From there, we can do all sorts of things with glucose.

Hexokinase is also inhibited by glucose-6-phosphate. So, the more we make, the less likely we are going to make it. Built in regulation making sure that we’re not storing too much in tissues…other than the liver, where glucose-6-phosphate does not effect glucokinase.

Now, sort of the counter to this is that we want to make sure that those other tissues get first crack, right? Storing glucose in the liver is not as important as making sure that muscles have enough energy, the heart, the CNS, right? So, because of that hexokinase actually has a higher affinity for glucose (low Km), which means that it really wants to bind to glucose and do its job. Glucokinase, then, has a low affinity (high Km), so it won’t bind quite so easily or quickly.

Kind of a short article this week, but those are important distinctions to know when understanding how the body best uses its energy sources. See you next week!