Human Physiology, 14th edition (2016)

Endocrine Glands 327

it to dissociate from the catalytic subunit, which then becomes

active ( fig. 11.8 ). In summary, the hormone—acting through an

increase in cAMP production—causes an increase in protein

kinase enzyme activity within its target cells.

Active protein kinase catalyzes the phosphorylation of

(attachment of phosphate groups to) different proteins in the

target cells. This causes some enzymes to become activated

and others to become inactivated. Cyclic AMP, acting through

protein kinase, thus modulates the activity of enzymes that are

already present in the target cell. This alters the metabolism of

the target tissue in a manner characteristic of the actions of that

specific hormone ( table 11.4 ).

Like all biologically active molecules, cAMP must be rap-

idly inactivated for it to function effectively as a second mes-

senger in hormone action. This inactivation is accomplished

this enzyme, which catalyzes the following reaction within
the cytoplasm of the cell:

A T P → cAMP 1 PPi
Adenosine triphosphate (ATP) is thus converted into
cyclic AMP (cAMP) and two inorganic phosphates ( pyro-
phosphate, abbreviated PPi). As a result of the interaction of
the hormone with its receptor and the activation of adenylate
cyclase, therefore, the intracellular concentration of cAMP is
increased. Cyclic AMP activates a previously inactive enzyme
in the cytoplasm called protein kinase. The inactive form of
this enzyme consists of two subunits: a catalytic subunit and a
regulatory subunit. The enzyme is produced in an inactive form
and becomes active only when cAMP attaches to the regula-
tory subunit. Binding of cAMP to the regulatory subunit causes

Figure 11.8 The adenylate cyclase–cyclic AMP second-messenger system. (1) The hormone binds to its receptor in
the plasma membrane of the target cell. (2) This causes the dissociation of G-proteins, allowing the free a (alpha) subunit to activate
adenylate cyclase. (3) This enzyme catalyzes the production of cAMP (cyclic AMP), which (4) removes the regulatory subunit from
protein kinase. (5) Active protein kinase phosphorylates other enzyme proteins, activating or inactivating specific enzymes and thereby
producing the hormonal effects on the target cell.

G-proteins

Plasma
Receptorprotein Hormone membrane

Adenylate cyclase

AT P

Protein kinase

(active)

cAMP + PPi

Regulatory subunit

cAMP

Phosphorylation

of proteins

Activation of

specific enzymes

Inactivation of

specific enzymes

Protein kinase

(inactive)

Regulatory subunit

1

2

3

4

5

β

γ

α

α α