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Coordinated Regulation of Glycolysis and Gluconeogenesis (PFK-1 and FBPase…
Coordinated Regulation of Glycolysis and Gluconeogenesis
Hexokinase isozymes
Four different isozymes
Isozyme IV
Glucose concentration at which it is half-saturated is much higher than usual concentration of glucose in blood. This lets it keep functioning as glucose concentrations rise
It's not inhibited by glucose-6-phosphate, so can continue to operate when others are out of commission
Allosterically inhibited by fructose-6-phosphate's inhibition of a specific regulatory protein only found in liver
PFK-1 and FBPase-1 are reciprocally Regulated
PFK-1 is allosterically inhibited by
ATP
Citrate
FBPase-1 is strongly allosterically inhibited by
AMP
Fructose 2,6 bisphosphate is also allosteric regulator
when this binds allosterically to PFK-1, it increases its affinity for fructose-6-phosphate and decreases its affinity for its inhibitors
Virtually inactive in its absence
concentration set by relative rates of formation and breakdown
it is formed by phosphorylation of fructose-6-phosphate, catalyzed by PFK-2 and broken down by FBPase-2
Glucagon stimulates release of cAMP, which activates c-AMP dependent protein kinase, phosphorylates bifunctional protein, and inhibits PFK-2 activity
Xylulose 5-phosphate activates PP2A, which activates PFK-2 and inhibits FPBase-2. This is a product of the pentose phosphate pathway. lots of glucose after eat big high-carb meal.
Pyruvate Kinase is allosterically inhibited by ATP
all isozymes inhibited by Acetyl CoA, ATP, and long-chain fatty acids
This shows that there's lots of energy
in addition, liver form is regulated by phosphorylation
when glucagon releases cAMP-dependent protein kinase, this phosphorylates the L isozyme and deactivates it
In muscle, when cAMP is released in response to epinephrine, glycogen breakdown and glycolysis is activated
fight or flight
Gluconeogenic conversion of pyruvate to PEP is under multiple types of regulation
When fatty acids are available, their breakdown gives acetyl-CoA, which signals that further glycolysis is unnecessary
Acetyl-CoA is a positive allosteric modulator for pyruvate carboxylase and a negative modulator of pyruvate dehydrogenase
Goes to oxaloacetate