Bc: Regulation Of Glucose Metabolism

Front 1

Fructose-2,6-bisPhosphate (F-2,6-bP)

Back 1

Regulates both glycolysis and gluconeogenesis.
-Allosteric Activator of PFK-1 (Glycolysis step 3)
-Allosteric Inhibitor of F-1,6-bisPhosphatase (reverse of glycolysis step 3; blocks gluconeogenesis)
-Created By?
-

Hint 1

Phosphorylation of F-6-P by Phosphofructokinase-2.

Front 2

Phosphofructokinase-2 (PFK-2)

Back 2

Bifunctional enzyme w/ two domains; One side phosphorylates F6P to create F-2,6-bP; Other side is a phosphatase that breaks down F-2,6-bP.
-Differential effects of phosphorylation in Liver/Muscle?

Hint 2

Liver: Phosphorylation of PFK-2 activates phosphatase, breaking down F-2,6-bP.
Muscle: Phosphorylation of PFK-2 activates kinase, creating F-2,6-bP.

Front 3

Glucagon

Back 3

Target tissue: Liver (liver ONLY)
Signals: Low Blood Glucose
Effect: decreases glycolysis, increases gluconeogenesis and glycogenolysis, leading to export of free glucose into blood.

Hint 3

Mechanism:
-Allosteric Inhibitor of F-2,6-bP, decreasing glycolysis and increasing gluconeogenesis and glycogenolysis.
-Increases [cAMP], inhibiting pyruvate kinase; forces PEP into gluconeogenesis & halts glycolysis.
-Promotes transcription of PEPCK gene; PEPCK is required for gluconeogenesis

Front 4

Insulin

Back 4

Targets: Liver and Muscle
Signals: High Blood Glucose
Effect (Overall): Lowered blood glucose
Effect (Liver): Increases glycolysis and glycogenesis; decreases gluconeogenesis and glycogenolysis
Effect (Muscle): Increases cellular uptake of glucose; increases glycogenesis.

Hint 4

Mechanism: Increases levels of F-2,6-bP by causing a cascade that ends with phosphorylation of PFK-2/F-2,6-bP'ase (?), the effects of which differ in liver and muscle.

Front 5

Epinephrine (Adrenaline)

Back 5

Target: Liver and Muscle (plus everywhere else)
Signals: Sympathetic Activation
Primary Effect (Muscle): Increased glycogenolysis, increased glycolysis; net effect is production of energy.
2' Effect (Liver): Increases glycogenolysis and gluconeogenesis, decreases glycolysis; net effect is export of free glucose

Hint 5

Mechanism:
-Liver: Binds beta-adrenergic receptor, causing increased [cAMP], DECREASING F-2,6-bP.
-Muscle: Binds beta-adrenergic receptor, causing increased [cAMP], INCREASING F-2,6-bP.

Front 6

*Effects of cAMP

Back 6

cAMP activates Protein Kinase A (PKA), which phosphorylates (?)
-Effectors that increase [cAMP]?

Hint 6

Glucagon and β-Adrenergic receptor activate Adenylate Cyclase, increasing [cAMP].

Front 7

Protein Kinase A (PKA)

Back 7

Phosphorylates PFK-2/F-2,6-bP'ase,
Liver: Activates F-2,6bPase, deactivates PFK-2; decreases [F-2,6-bP].
Muscle: Activates PFK-2; increases [F-2,6-bP], increasing glycolysis.
Activated by:?
Other effects?

Hint 7

Activated by increased [cAMP]; Inhibited by insulin-signaling cascade.

Front 8

Citrate

Back 8

Inhibits glycolysis and upregulates gluconeogenesis. If you have plenty of citrate for the TCA cycle, you probably don't need more pyruvate.