Exam II

Question 1

*The activity of PTEN will do what?

Answer 1

DIMINISHES insulin activity by removing 3’rd phosphate from PIP3 back to PIP2.

Question 2

Are glucagon receptors the same thing as Epinephrine receptors?

Answer 2

Essentially yes. Epinephrine are broader and exist more quantitatively. Glucagon is more specific.

Question 3

Which organs do glucagon exist?

Answer 3

adipose tissue and the liver.

Question 4

What type of receptor is the glucagon receptor?

Answer 4

G-protein receptor.

Question 5

Describe the glucagon signaling from the first step of binding to the receptor to the activation of cAMP

Answer 5

1) Glucagon binds to receptor causing conformational change across the membrane 2) having a different interaction with the G protein, 3) alpha subunit the exchanges a GDP with a GTP, 4) causing the alpha subunit to release from the G-protein and move laterally across the membrane, 5) until it reaches Adenylyl cyclase which make cAMP

Question 6

What does cAMP then do after it has been activated by Adenylyl Cyclase?

Answer 6

cAMP bind to PKA which then activates PKA through releasing the catalytic subunit from PKA which is now available to go on and phosphorylate things.

Question 7

How is glucagon signaling reversible?

Answer 7

cAMP is broken down by cyclic nucleotide phosphodiesterase. This is also converting cAMP to AMP but when the glucagon signaling is present cAMP overwhelms what cyclic nucleotide phosphodiesterase can handle.

Question 8

What pathways need to be activated within the liver in response to low blood glucose?

Answer 8

Glycogen breakdown and GNG.

Question 9

How is glycolysis deactivated while at the same time activating GNG in the liver when their is low blood sugar?

Answer 9

By a decrease in [] of F26BP (Fructose 2,6-bisphosphate) F26BP is not able to inhibit FBPase-1 which inhibits GNG under high [] pf F26BP therefore allowing GNG to occur. At the same time a decrease in [] of F26BP reduces F26BP activating effect on PFK-1 which promote glycolysis and thus slows down glycolysis.

Question 10

What makes Fructose 2-6 Bisphosphate and what breaks it down?

Answer 10

Fructose 2,6-bisphosphate can be made from Fructose 6-phosphate by PFK-2. F2-6BP can also be broken down by FBPase-2 back to F6P.

Keep in mind this is different from PFK-1 which catalyzes the phosphorylation of fructose-6-phosphate to fructose-1,6-bisphosphate in glycolysis and, FBPase-1 which catalyzes the hydrolysis of fructose 1,6-bisphosphate to fructose 6-phosphate in gluconeogenesis

Question 11

Where is PFK-2 and FBPase-2 found?

Answer 11

On a bifunctional enzyme called PFK2/FBPase-2

Question 12

How is PFK-2/FBPase-2 regulated?

Answer 12

When the kinase domain (PFK-2) is phosphorylated, PFK-2 is inactive and the FBPase-2 is then active.

Note PFK-2 activaty promotes glycolysis in the liver. When FBPase-2 is active in the liver it promotes GNG.

Question 13

What enzyme is most likely to phosphorylate the N-terminal domain of PFK2/FBPase2?

Answer 13

PKA

Question 14

What is PKA also known as?

Answer 14

cAMP-dependent Protein Kinase

Question 15

***Describe the steps in GNG in the liver from Adenylyl cyclase to the inhibition of the molecule F26BP.

Answer 15

From Adenylyl cyclase, it makes cAMP (using ATP) and cAMP binds to PKA which cause PKA to release it’s catalytic domain to go on to phosphorylate the bifunctional enzyme PFK-2/FBPase-2 which will deactivate PFK-2 and activate FBPase-2 to break down F26BP which with a lower [] F26BP relieve inhibition of FBPase-1 to turn on GNG

Question 16

What happens to Pyruvate Kinase in the liver when glucose levels are low?

Answer 16

Glucagon will will activate PKA and PKA will phosphorylate Pyruvate kinase (the last regulatory step in glycolysis) and make pyruvate kinase inactive.