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An important point about glycogen metabolism is the functionality of glycogen phosphorylase. This enzyme is most upstream and breaks down glycogen from its most branched form.
Now what I’m about to write is going to sound really ridiculous and pedantic:
During the fasting state, glycogen phosphorylase and glycogen phosphorylase kinase are activated and phosphorylated.
| Mike, the USMLE seriously cares about enzyme phosphorylation? Yeah. |
Glycogen phosphorylase kinase is simply the enzyme that phosphorylates and activates glycogen phosphorylase.
Both are phosphorylated AND activated during the fasting state.
| ^ Yes, just memorize that. I promise I’m not wasting your time. |
The way to approach this topic is to know that insulin generally causes dephosphorylation of enzymes.
So for starters:
| Fed state? → insulin high → enzymes dephosphorylated
Fasting state? → insulin low → enzymes phosphorylated |
Then we have:
| Fed state? → we expect anabolic enzymes active + catabolic enzymes inactive
Fasting state? → we expect catabolic enzymes active + anabolic enzymes inactive |
So now let’s combine the two:
| Fed state? → insulin high + anabolic enzymes active + catabolic enzymes inactive
Fasting state? → insulin low + catabolic enzymes active + anabolic enzymes inactive |
Now finally, introducing the phosphorylation aspect:
| Fed state? → insulin high → anabolic enzymes dephosphorylated + active; catabolic enzymes dephosphorylated + inactive
Fasting state? → insulin low → catabolic enzymes phosphorylated + active; anabolic enzymes phosphorylated + inactive |
So for instance, PFK2 is an anabolic enzyme, so if they tell you a guy just ate a turkey dinner, you’d say:
“Ok, well insulin would be high. Therefore, whatever enzyme they’re asking about would be dephosphorylated. Because PFK2 is anabolic, it’s clearly going to be active in the fed state, so we can say it’s dephosphorylated and active.”
Sound really dry and boring? Yeah, I know. But the USMLE doesn’t give a fuck about how dry you think this is. The rule is that whatever you choose not to study is going to be exactly what shows up on your test.
The reason the phosphorylative processes occur as they do is because insulin is always in a balance with glucagon. The latter up-regulates cAMP synthesis, which activates protein kinase A (PKA), which in turn phosphorylates enzymes. Insulin, however, despite acting through a MAP kinase, ultimately leads to activation of protein phosphatases that dephosphorylate enzymes.
| Really annoying detail that seemingly contradicts the above:
If you are ever asked in a question about insulin’s effect on intracellular signaling, it phosphorylates via MAP in order to ultimately increase gene transcription. But when we’re talking about the macro effect of enzyme activation / inactivation, insulin dephosphorylates. This is asked on one of the NBMEs (i.e., when insulin binds to its receptor, what happens in its signaling pathway → yes, phosphorylation; yes, gene transcription; no, no proteolysis). |
Two other points:
Although glucagon secretion during exercise (fasting state) contributes to maintenance of blood glucose levels, if they ask you what ensures that muscle contraction/activity is coordinated with glycogen breakdown, the answer is calcium.
You need to know that calcium/calmodulin leads to the phosphorylation and activation of glycogen phosphorylase kinase. Although calmodulin is responsible for contraction only in smooth muscle, in skeletal muscle, it still has a major role in regulation of glycogen catabolism.
And the other key detail: glucocorticoid (i.e., cortisol) INCREASES glycogen synthesis, despite being catabolic in muscle/adipose tissue.
| You would think that because cortisol is catabolic it would increase glycogenolysis, but it instead increases glycogenesis (at least in USMLE questions). |
That’s pretty much it on this annoying topic.
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