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CASE FILES: BIOCHEMISTRY
different G protein families are presented in Table 7-1. Common effector
enzymes are adenylate cyclase, which converts ATP into 3',5'-cyclic AMP
(cAMP) and phospholipase C (PLC), which hydrolyzes the membrane lipid
phosphatidylinositol-4,5-bisphosphate (PIP2) to diacylglycerol and inositol-
1,4,5-triphosphate (IP3). While GTP is bound to the a-subunit, the interaction
with the effector enzyme continues. However, the a-subunit also contains an
intrinsic GTPase activity that will hydrolyze GTP to GDP and inorganic
phosphate (Pi). This provides a mechanism by which the hormonal signal can
be switched off, because GTP hydrolysis to GDP causes the a-subunit to
release the effector enzyme and reassociate with the Py subunits.
The hormonal cascade known as the hypothalamic-pituitary-thyroid axis
employs G-protein transducers that activate both adenylate cyclase and
phospholipase C. After receiving an electrochemical signal from the central
nervous system (CNS), thyrotropin-releasing hormone (TRH) is released from
the arcuate nucleus and median eminence of the hypothalamus. TRH is car-
ried to the anterior pituitary via long portal vessels. In the anterior pituitary,
TRH binds to G protein-coupled TRH receptors on the cell surface of
thyrotrophs. This activates phospholipase C, releasing both DAG and IP3.
DAG activates protein kinase C (PKC), which phosphorylates target pro-
teins. The release of IP3 opens Ca2+ channels in the endoplasmic reticulum,
thus releasing Ca2+ from storage and increasing cytoplasmic [Ca2+]. Both of these
events result in the increase in synthesis and release of thyrotropin, also known
as thyroid-stimulating hormone or TSH, which is stored in secretory granules
within the thyrotroph. Circulating TSH binds to TSH receptors on the basolat-
eral membranes of the thyroid follicular cell. The TSH receptor is a G pro-
tein-coupled receptor that activates adenylate cyclase to produce cAMP
when hormone is bound. The increase in cAMP triggers a series of events
Table 7-1
G-PROTEIN FAMILIES AND THEIR FUNCTIONS
G CLASS
a
INITIATING SIGNAL
DOWNSTREAM SIGNAL
G
s
P-Adrenergic amines, glucagon,
parathyroid hormone, thyrotropin
(TSH), corticotrophin, many others
Stimulates adenylate cyclase
G.
1
Acetylcholine, a-adrenergic amines,
many neurotransmitters, chemokines
Inhibits adenylate cyclase
G
q
Acetylcholine, a-adrenergic amines,
Increases IP3 and
TRH, many neurotransmitters
intracellular calcium ion
Gt
Photons
Stimulates cGMP
(Transducin)
phosphodiesterase
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