Question

14 A) Which of the following events occur during the epinephrine-stimulated conversion of glycogen to glucose-1-phosphate?

All of the answers are correct.

activation of PKA by cAMP

activation of glycogen phosphorylase

inhibition of glycogen synthase

14 B) Which type of experimental evidence shows that the intrinsic GTPase activity of the G? subunit is important for terminating effector activation?

A nonhydrolyzable GTP analog that can bind to the G? subunit but cannot be hydrolyzed by the intrinsic GTPase, thereby activating the effector protein longer upon ligand-induced activation of the receptor.

A dominant negative (no activity) GEF causes stimulation of the effector protein for longer upon ligand-induced activation of the receptor.

A dominant active (constant activity) GEF causes stimulation of the effector protein for longer upon ligand-induced activation of the receptor.

A nonhydrolyzable GTP analog causes displacement of GDP with the modified GTP resulting in continuous activation of the receptor because the bound GTP analog cannot be hydrolyzed to GDP.

Answer 1

14. A. The correct answer is the first option - all of the answers are correct.

Epinephrine - stimulated conversion requires all the steps. cAMP as a second messenger activates protein kinase A. Glycogen phosphorylase adds phosphate group to the glucose and converts to glucose 1 - phosphate. Inhibition of glycogen synthase is essential. This is due to the activity of epinephrine which triggers glucose release from glycogen.

14 B. The correct answer is the last option - A nonhydrolyzable GTP analog causes displacement of GDP with the modified GTP resulting in continuous activation of the receptor because the bound GTP analog cannot be hydrolyzed to GDP.

The role of the intrinsic GTPase of the G subunit has been investigated using GTP analogs that can bind to the G subunit but cannot be hydrolyzed by the intrinsic GTPases. In these nonhydrolyzable compounds, the terminal phosphodiester (P-O-P) bond in GTP is replaced with P-CH2-P or P-NH-P bonds. In the presence of these nonhydrolyzable GTPs, the response of the effector protein is prolonged upon ligand-induced activation of the receptor. This is because the displacement of GDP with the modified GTP results in continuous activation of the effector protein. Because the bound GTP analog cannot be hydrolyzed to GDP, the effector remains in an active state permanently.