Regulation of Carb Metabolism - RR Flashcards
What are the three regulatory enzymes in glycolysis?
- Hexokinase
- Phosphofructokinase
- Pyruvate kinase
PFK has two allosteric sites for ATP. How are these two sites different? Why is this important for regulation?
One of the ATP sites has a high affinity for ATP- need to the ATP as part of the reaction to get F-1,6-BP
The other ATP site has a low affinity for ATP. ATP and AMP compete for a position in the second allosteric site. When there’s a lot of ATP, ATP binds which places two like charges next to each other and destabilizing PFK.
How does PFK respond to increased levels of F-2,6-BP? Where does F-2,6-BP bind?
Stimulates the activity of PFK
F-2,6-BP binds to the low affinity ATP allosteric site, preventing ATP from binding and thus stimulating PFK
How do F-2,6-BP and AMP affect PFK and FBPase?
Stimulate PFK
Inhibit FBPase
What are the enzymes that are used to bypass the three regulatory steps of glycolysis when performing gluconeogenesis?
- Pyruvate carboxylase with PEPCK
- Fructose bisphosphate phosphatase (FBPase)
- Glucose-6-phosphatase
What enzyme controls the synthesis and breakdown of F-2,6-BP?
Bifunctional enzyme- has both phosphatase and kinase activity
When bifunctional enzyme is phosphorylated, what part of the enzyme becomes active? What does this mean for the synthesis/breakdown of F-2,6-BP? How does it relate to the activity of FBPase and PFK?
Phosphatase gets activated
Remove the phosphate from F-2,6-BP so decrease the levels of F-2,6-BP
Activation of FBPase and inhibition of PFK
What molecules/hormones are responsible for phosphorylating bifunctional enzyme?
Glucagon
Glucagon binds to a GCPR that then activates adenylate cyclase and increase cAMP which phosphorylates the bifunctional enzyme and increases the phosphatase activity
What molecules/hormones are responsible for dephosphorylating bifunctional enzyme?
Insulin
Get removal of the phosphate and kinase activity of the bifunctional enzyme. Leads to increased production of F-2,6-BP, activation of PFK and inhibition of FBPase
How do F-1,6-BP, acetyl CoA, and ATP affect pyruvate kinase?
F-1,6-BP stimulates pyruvate kinase
Acetyl CoA and ATP inhibit pyruvate kinase
When pyruvate kinase is phosphorylated is it active or inactive?
Inactive
glucagon phosphorylates pyruvate kinase
How does acetyl CoA affect pyruvate carboxylase?
Activates pyruvate carboxylase
What two enzymes involved in glycogen synthesis and degradation are regulated?
glycogen synthase (adds UDP-glucose to growing glycogen) glycogen phosphorylase (glycogen breakdown)
When is phosphorylase kinase active? How does active phosphorylase kinase affect glycogen synthase and glycogen phosphorylase?
Activated when phosphorylated
Phosphorylates both glycogen synthase and glycogen phosphorylase
Deactivates glycogen synthase and activates glycogen phosphorylase
How does glucagon stimulate muscle cells?
Stimulates insuline secretion that binds to insulin receptor on muscles and stimulates glucose intake
