Question

Stimulation of a certain Gs protein–coupled receptor activates protein kinase A (PKA). Predict the effect of PKA activation on the following substrates of PKA: (a) acetyl-CoA carboxylase, (b) glycogen synthase, (c) hormone-sensitive lipase, and (d) phosphorylase kinase.

Short answer

Acetyl-Co carboxylase and glycogen synthase will be inhibited when PKA is activated. Hormone-sensitive lipase and phosphorylase kinase will have the reverse effect, increasing their activity.

Step-by-step solution

Protein kinase A

PKA (also known as cAMP-dependent protein kinase or cAPK) is an enzyme that phosphorylates Threonine and Serine residues in a variety of biological proteins.

(a) Acetyl-CoA carboxylase

Acetyl-CoA carboxylase is a catalytic enzyme that catalyzes the irreversible carboxylation of acetyl-CoA to malonyl-CoA. Malonyl-CoA is an intermediary substrate that plays a role in fatty acid metabolism regulation. Phosphorylation inhibits acetyl-CoA carboxylase. Because PKA catalyzes phosphorylation activities, it will impede the action of Acetyl-CoA carboxylase.

(b) Glycogen synthase

The rate-determining phase of glycogenesis, glycogen synthesis, is regulated by glycogen synthase (GS). It is triggered by insulin-induced dephosphorylation and inactivation of GS kinase-3. On the other hand, PKA phosphorylates glycogen synthase, switching it from an active to an inactive state.

(c) Hormone-sensitive lipase

The hydrolysis of acylglycerols, triacylglycerols, and esters is catalyzed by hormone-sensitive lipase. Lipolysis, or the breakdown of triacylalycerols into free fatty acids and glycerol, is regulated by this protein. PKA activation causes hormone-sensitive lipase to be phosphorylated, transforming it into an active form.

(d) Phosphorylase kinase

Phosphorylase kinase catalyzes the phosphorylation of glycogen phosphorylase b (less active) to generate glycogen phosphorylase a (more active), allowing glucose-1-phosphate to be released from glycogen during glycogenolysis. The phosphorylation process performed by PKA activates Phosphorylase Kinase.