[Heli0x]

Hi everyone, I'm only attending my first biochem course so please bear with me.

The scenario of four different Hexokinase izoenzymes confuses me somewhat. Not the the fact that there are four of them, but that the fourth one is excluded from the regulative rules which apply for the first three ones.

Why is it that, Hk I-III are inhibited by G-6-P, but the Hk IV isn't?

The way I see it, it seems pretty pointless in having four izoenzymes, where the first three are inhibited by G-6-P, effectively stopping glucolysis, while the fourth one just keeps on chewing up those glucose-molecules while at the same time rendering the whole existence of the former three pretty much useless (in my faulty idea of how it works, that is).

Basically what I'm asking is: What is the role of Hk IV (Glucokinase) and how is it regulated? (Does Hk IV only exist within the liver, or does it appear in the muscle cells as well?)

[BioBell]

Glucokinase (hexokinase D or IV) exists in the liver and the beta cells of the islet of langerhans in the pancreas.

GK is different to other HKs because it has a much higher Km value, which means it requires a higher glucose concentration for half saturation.
As a result, GK only functions when the intracellular concentration of glucose in the liver cell (hepatocyte) is elevated, for example, the period following ingestion of carbohydrate when you get a high level of glucose being delivered to the liver via the portal vein.

GK has a high Vmax which means the liver can effectively remove the glucose being delivered via the portal blood.
This prevents a large amount of glucose from entering the circulation following carbohydrate ingestion which minimises hyperglycaemia (don't confuse it with hypoglycaemia).

Also GK is not directly inhibited by its reaction product G6P - it is indirectly inhibited by fructose 6 phosphate which is in equilibrium with G6P and indirectly stimulated by glucose.

I hope this makes sense to you 

[Heli0x]

It cleared up a bit, thanks!