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Why is ATP an inhibitor? I mean, if there are high levels of ATP, it means that the cell has adequate amounts of energy. Therefore, if it doesn't need the energy, then glucose needs not go through glycolysis to produce that energy and is more practical to be stored as glycogen. So why is ATP an inhibitor of glycogen synthase?

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  • $\begingroup$ Maybe I'm misreading the question, but it sounds like it would be more fitting on Biology SE. It sounds like you are asking why physiologically this occurs rather than what chemically causes ATP to inhibit it. $\endgroup$ – Tyberius Apr 17 '17 at 14:29
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Firstly, I will put across main points so that it will be easy to understand this complex control mechanisms of the enzymes involved in both processes:

Glycogen synthase control

Control of glycogen metabolism is effected via reciprocal regulation of glycogen phosphorylase and glycogen synthase. Thus, activation of glycogen phosphorylase is tightly linked to inhibition of glycogen synthase, and vice versa.

Both glycogen synthesis and breakdown are exergonic under the same physiological conditions. If both pathways operate simultaneously, however this is deemed to be wasteful hydrolysis of UTP.

Glycogen phosphorylase and glycogen synthase therefore must be under stringent control such that glycogen is either synthesized or utilized according to cellular needs. Regulation involves both allosteric control and covalent modification, with the latter being under hormonal control.

Glycogen synthase also exists in two distinct forms that can be interconverted by the action of specific enzymes: active, dephosphorylated glycogen synthase I (glucose- 6-P–independent) and less active, phosphorylated glycogen synthase D (glucose-6- P–dependent). Glycogen synthase, is activated by G6P.When there is high demand for ATP (low [ATP], low [G6P], and high [AMP]), glycogen phosphorylase is stimulated and glycogen synthase is inhibited, so flux through this pathway favours glycogen breakdown.

Why is this so?

ATP also binds to the allosteric effector site, but in the T state, so that it inhibits rather than promotes the T-R conformational shift. Having said that here is an illustration of control of glycogen phosphorylase activity;

glycogen- enzymes

The enzyme may assume the enzymatically inactive T conformation or the catalytically active R form. The conformation of phosphorylase b is allosterically controlled by effectors such as AMP, ATP, and G6P and is mostly in the T state under physiological conditions. In contrast, the modified form of the enzyme, phosphorylase a, is largely unresponsive to these effectors and is mostly in the R state unless there is a high level of glucose.

Exactly this situation occurs in glycogen metabolism through the opposition of the glycogen phosphorylase and glycogen synthase reactions.

Another point to note is that glycogen synthase is regulated by covalent modification through complex cyclic cascade. For more information, please see here: Glycogen Metabolism

If you need more clarification don't hesitate to put in comments. Hope it helps

References

  1. Biochemistry (Grisham)
  2. Biochemistry (Voet and Voet)
  3. Harper’s Illustrated Biochemistry
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  • $\begingroup$ ATP was mentioned to be an inhibitor of glycogen synthase (Campbell and Farrell, 2009). However, in the book it gives no further explanation about this. What I seem to get from your answer is that ATP inhibits the transition to R state of glycogen phosphorylase which is besides the point. However, thanks for the note on the controls of ATP on both enzymes. I just cant really get why the aforementioned authors said that ATP inhibits glycogen synthase. $\endgroup$ – angrycarbocation Apr 17 '17 at 14:30
  • $\begingroup$ @angrycarbocation remember the two enzymes are reciprocal and yes ATP is an inhibitor, that's what I was explaining in the answer. Read bold words please, the enzymes essentially "act" the same way although the for different pathways $\endgroup$ – xavier_fakerat Apr 17 '17 at 14:33
  • $\begingroup$ (low [ATP], low [G6P], and high [AMP]), glycogen phosphorylase is stimulated and glycogen synthase is inhibited Is ATP still an inhibitor of glycogen synthase or is it for glycogen phosphorylase? $\endgroup$ – angrycarbocation Apr 17 '17 at 14:37
  • $\begingroup$ What I got from the explanation and the bold words is that ATP is an inhibitor of the phosphorylase and not the synthase which is a direct contradiction of the statement in my reference. $\endgroup$ – angrycarbocation Apr 17 '17 at 14:40
  • $\begingroup$ @angrycarbocation it is essentially true for glycogen synthase . ATP is an allosteric effector for glycogen synthase hence inhibitor and that what's in the answer, for illustration I had to use the other enzyme but it's very similar to glycogen synthase $\endgroup$ – xavier_fakerat Apr 17 '17 at 14:41

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