594
UNIT 3
Regulation and Integration of the Body
16
one of these second messengers,
cyclic AMP (cAMP)
, which is
used by neurotransmitters (Chapter 11) and olfactory receptors
(Chapter 15).
The Cyclic AMP Signaling Mechanism
As you recall, this
mechanism involves the interaction of three plasma membrane
components—a hormone receptor, a G protein, and an effector
enzyme (adenylate cyclase)—to determine intracellular levels of
cyclic AMP.
Figure 16.2
illustrates these steps:
1
Hormone binds receptor.
Te hormone, acting as the
first
messenger
, binds to its receptor in the plasma membrane.
2
Receptor activates G protein.
Hormone binding causes the
receptor to change shape, allowing it to bind a nearby inac-
tive
G protein
. Te G protein is activated as the guanosine
diphosphate (GDP) bound to it is displaced by the high-
energy compound
guanosine triphosphate
(
GTP
). Te G
protein behaves like a light switch: It is “off” when GDP is
bound to it, and “on” when G±P is bound.
3
G protein activates adenylate cyclase.
Te activated G pro-
tein (moving along the membrane) binds to the effector
enzyme
adenylate cyclase
. Some G proteins (G
s
)
stimulate
adenylate cyclase (as shown in Figure 16.2), but others
(G
i
)
inhibit
adenylate cyclase. Eventually, the G±P bound
to the G protein is hydrolyzed to GDP and the G protein
becomes inactive once again. (Te G protein cleaves the
terminal phosphate group off G±P in much the same way
that A±Pase enzymes hydrolyze A±P.)
4
Adenylate cyclase converts ATP to cyclic AMP.
For as long
as activated G
s
is bound to it, adenylate cyclase generates
the
second messenger
cAMP from A±P.
5
Cyclic AMP activates protein kinases.
cAMP, which is free
to diffuse throughout the cell, triggers a cascade of chemi-
cal reactions by activating protein kinases.
Protein kinases
are enzymes that
phosphorylate
(add a phosphate group to)
various proteins, many of which are other enzymes. Be-
cause phosphorylation activates some of these proteins and
inhibits others, it may affect a variety of processes in the
same target cell at the same time.
Tis type of intracellular enzymatic cascade has a huge am-
plification effect. Each activated adenylate cyclase generates
large numbers of cAMP molecules, and a single kinase enzyme
Hormone (1st
messenger)
binds receptor.
Receptor
activates G
protein (G
s
).
G protein
activates
adenylate
cyclase.
cAMP activates
protein kinases.
Adenylate
cyclase converts
ATP to cAMP
(2nd messenger).
Receptor
G protein (G
s
)
Adenylate cyclase
Triggers responses of
target cell (activates
enzymes, stimulates
cellular secretion,
opens ion channel, etc.)
Inactive
protein
kinase
Extracellular fluid
Cytoplasm
Active
protein
kinase
ATP
GTP
GTP
cAMP
GTP
GDP
5
4
3
2
1
Hormone
(1st messenger)
Receptor
G protein
Enzyme
2nd
messenger
Recall from Chapter 3 that
G protein signaling mechanisms
are like a molecular relay race.
Figure 16.2
Cyclic AMP second-messenger mechanism of water-soluble hormones.
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