In Chapter 9 and in Chapter 11, you will be given bits and pieces of the cAMP cascade and they will not be presented in the book in the order they happen in the cell.  As you progress through the course, you will learn more about the cascade and be expected to add even more of the steps. The cAMP cascade begins when a hormone binds to a receptor on a cell membrane and ends with a change in the rates of many key enzymes reactions and in the concentrations of the key metabolites that they control.  For this class, we will begin the cAMP cascade with adrenalin (epinephrine) or glucagon binding to receptors and end with the release of glucose from glycogen.  In later chapters, we will learn the effect of this cascade upon glycolysis, gluconeogenesis, fatty acid synthesis, and fatty acid mobilization and oxidation. Remember that this pathway will be discussed throughout the course and you are not expected to thoroughly understand it at this time.  At this time, you only need to know the parts of the pathway that pertain to the Objectives in Chapter 6.

The sequence of events follows:

Adrenalin binds to a Beta-adrenergic receptor or glucagon binds to a glucagon receptor and causes a change in conformation.  Since every step in the cascade depends upon a change in conformation we will not mention it anymore.  This binding is shown in Fig 11.10.

The receptor binds to a heterotrimeric G-protein on the inside of the membrane.  This is not the monomeric G-protein talked about in Fig 9.11 but the one shown in Fig 11.10.  From now on, we will just call it a Gs (“G sub S” or “G stimulatory protein”).  Binding causes the Gs protein to dissociate from GDP and associate with GTP.  The binding of GTP causes the dissociation of the beta (β) and gamma(γ) subunits from the alpha(α) subunit.  See Figure 11.17.  Note that the subunits α and γ subunits are tethered to the intracellular side of the plasma membrane through lipid anchors.

The Gsα subunit binds to and activates adenylate cyclase (adenylyl cyclase).  Adenylate cyclase stays active until the GTP is hydrolyzed to GDP.  When GTP is hydrolyzed, the Gs-α subunit dissociates from the adenyl cyclase and is ready for another cycle.

Active adenylate cyclase converts ATP to cAMP (3’,5’-cyclic AMP).  See Figure 11.18.  (The PPi is Pyrophosphate.  See Fig. 23.2 for structure)

The cAMP diffuses away from the inner membrane and binds to inactive Protein Kinase A (PKA, Fig 9.9).  This dissociation of the regulatory subunits causes activation of the active subunits.

The active subunits cause the phosphorylation of many proteins (Fig 9.7) but here we will concentrate on glycogen phosphorylase kinase (also called phosphorylase kinase, Figure 9.8).  Glycogen phosphorylase kinase is eventually inactivated by dephosphorylation by a protein phosphatase (Fig. 9.7)

Glycogen phosphorylase kinase phosphorylates and, thus, converts glycogen phosphorylase b into glycogen phosphorylase a (also called phosphorylase a, Fig 9.8).  Glycogen phosphorylase a is an active form of the enzyme and will remain active until it is de-phosphorylated.

Glycogen phosphorylase a causes the removal of glucose units from glycogen in the form of glucose-1-phosphate.  The glucose is used for glycolysis in muscle and to produce blood glucose in the liver (Fig 28.3).

You might develop your own short version of the cAMP cascade as the course proceeds. In the mean time,here is one that you can use.

Hormone + Receptor + Gαβγ-GDP = Hormone-Receptor-Gαβγ-GDP
Hormone-Receptor-Gαβγ-GDP + GTP = Hormone-Receptor + GDP + Gβγ +Gα-GTP
Gα-GTP + Adenylate cyclase = Gα-GTP-Adenylate cyclase
ATP = cAMP + PPi 
cAMP + PKARRCC = 2 cAMP-R + 2 PKA
Inactive phosphorylase kinase + ATP = active phosphorylase kinase + ADP
Inactive phosphorylase b + ATP = active phosphorylase a + ADP
Glycogen + Pi = Glycogen + Glucose-1-P
Glucose-1-P = Glucose-6-P