Why is glycogen not directly converted to glucose by hydrolysis in the liver?

[chemicallyconfused]

In the liver, the glucose stored in glycogen molecules is liberated via phosphorolysis in the form of glucose-1-phosphate in a reaction catalized by the enzyme glycogen phosphorylase. Glucose-1-phosphate is then converted to G6P by action of an enzyme called Phosphoglucomutase. And, finally, G6P is converted to free glucose by the enzime glucose-6-phosphatase. This free glucose is now ready to leave the liver and enter the bloodstream.

My doubt is: why is not the glucose stored in glycogen directly converted to free glucose by hydrolysis? Instead of following the longer path: Glycogen -> G1P -> G6P -> Free glucose.

Thanks in advance, and sorry if there are any grammatical errors, as English is not my first language.

Edited October 9, 2013 by chemicallyconfused

[BabcockHall]

I don't know the answer, but I am happy to speculate. Although liver stores of glycogen can be converted into glucose and exported (this is obviously a major pathway), that is not its only possible fate. It can proceed through glycolysis or be converted into other carbohydrates, such as galactose. These are both more sensibly done through glucose phosphates.

[hypervalent_iodine]

The direct hydrolysis would require an acidic environment and I suspect that such an environment is not very good for the liver. The use of enzymes also offers a feedback mechanism and a greater degree of control over when the glucose is released.

[BabcockHall]

Both glycogen phosphorylase and glucose 6-phosphatase are regulated enzymes, and the ability to regulate them independently may be important in some circumstances.

[CharonY]

As hypervalent_iodine mentioned, non-enzymatic hydrolysis is not going to work in the given environment. Also, enzymatic degradation is not quite trivial as glycogen is highly branched. The whole process is a bit more complicated. The glycogen phosphorylase releases G1-P from linear glucosidic bonds (1->4 bonds), but is not able to work near the branches (1->6 bonds.) Here, another enzyme has to act (debranching enzyme) in order to create a debranched limit dextrin, which allows the glycogen phosphorylase to act again.

[BabcockHall]

I don't believe that the question posed by the OP had anything to do with nonenzymatic hydrolysis (which would require an acidic environment) I think it was more along the lines of why is there no enzyme "glucose hydrolase" that would break glycogen down directly to glucose. There would still need to be a debranching enzyme, as CharonY pointed out.

[Ringer]

I don't believe that the question posed by the OP had anything to do with nonenzymatic hydrolysis (which would require an acidic environment) I think it was more along the lines of why is there no enzyme "glucose hydrolase" that would break glycogen down directly to glucose. There would still need to be a debranching enzyme, as CharonY pointed out.

That can be answered rather simply, evolution doesn't care about absolute efficiency. Asking why there isn't something that would do a better job in a living system is like asking why the naturally made path down a mountain isn't the most efficient way.

[BabcockHall]

If an ancestral glycogen catabolase simply broke down glycogen to run through glycolysis, then having the nucleophile be phosphate definitely confers an advantage. If this enzyme later became liver glycogen phosphorylase, then I can see why a glycogen hydrolase for liver might not have evolved. However, I have to wonder whether having two points of control (glycogen phosphorylase and glucose 6-phosphatase), might confer some ability to fine tune how much glucose gets created and from which of two sources (glycogen versus pyruvate and related glucogenic compounds). Just thinking out loud.

[iRNAblogger]

The way that I would rationalize phenomenon (to myself, meaning it is just how I think about/explain it, not how it actually is) would be through the "lens" of control. Non-phosphorylated glucose can easily diffuse out of the cell (I forget if it can actually pass through the membrane, or if it diffuses out of channels...), but phosphorylated glucose does not. This explanation is the rationalization for why glucose transportation is dependent on hexokinase activity: it 1. prevent the glucose from being able to diffuse back out of the cell and 2. preps the glucose for glycolysis and other metabolic processes.

 

Thinking about your question in this way, it would make more sense to go through glycogen phophorolysis over hydrolysis because then the liver cells can control where the glucose ends up. If there is a need to export the glucose to the blood stream, then that pathway will be favored; if the cells themselves are ATP deficient, then the metabolic pathway will be favored, etc.. With hydrolysis, it might actually be LESS efficient because if the cell decides that it needs more ATP, then it has to wait for the glucose to randomly collide with a hexokinase within the cell and it also runs the risk of losing the glucose (because it may diffuse out of the cell). This explanation is how I would explain this phenomenon to myself (I'm not sure if this explanation was already implied by other answers, but I didn't see mention of it within this thread)

Edited October 17, 2013 by iRNAblogger