Sciencemadness Discussion Board

Protein Kinase A / Pyruvate Kinase Regulation Confusion

Fuaaark - 13-7-2011 at 20:38

Edit.

I guess what I'm really confused about is why protein kinase A (activated by epinephrine pathway that leads to glycogen breakdown) deactivates pyruvate kinase (which catalyzes glycolosis.

Seems to me like PKA should be activating pyruvate kinase if anything.

[Edited on 14-7-2011 by Fuaaark]

[Edited on 14-7-2011 by Fuaaark]

Protein Kinase A / Pyruvate Kinase Regulation Confusion

Fuaaark - 13-7-2011 at 20:54

Hey,

Why does protein kinase A deactivate pyruvate kinase?

PKA starts breakdown of glycogen to glucose.
Pyruvate kinase is a critical part of glycolysis.

ThatchemistKid - 12-11-2011 at 08:35

I see how this is confusing, I could not see the reason why this occurred either. You are missing a key piece of information though, PKA only inhibits the pyruvate kinase of the liver but not of the muscle ..so conceivably during the fight or flight response associated with the release of epinephrine the liver stops using sugar to make more available for the muscle. Also, the pyruvate kinase of the liver is inhibited during "starvation times" leading to more sugar for the brain and muscle and eventually to ketone bodies for the brain and heart.

here is an exert from the wiki on pyruvate kinase.

Liver pyruvate kinase is also regulated indirectly by epinephrine and glucagon, through protein kinase A. This protein kinase phosphorylates liver pyruvate kinase to deactivate it. Muscle pyruvate kinase is not inhibited by epinephrine activation of protein kinase A. Glucagon signals fasting (no glucose available). Thus, glycolysis is inhibited in the liver but unaffected in muscle when fasting. An increase in blood sugar leads to secretion of insulin, which activates phosphoprotein phosphatase I, leading to dephosphorylation and activation of pyruvate kinase. These controls prevent pyruvate kinase from being active at the same time as the enzymes that catalyze the reverse reaction (pyruvate carboxylase and phosphoenolpyruvate carboxykinase), preventing a futile cycle.

On top of this the sensitivity of the liver hexose kinase is much higher than the glucokinases in other parts of the body so inhibition of liver glycolysis during fight or flight is beneficial.

[Edited on 12-11-2011 by ThatchemistKid]