Chap. 15 Problem 2

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Chap. 15 Problem 2
Signaling systems are classified based on the
distance over which they act. Endocrine signaling
acts over long distances within the organism.
Paracrine signaling acts over a very short
distances, for example between neighboring cells.
In autocrine signaling, cells release ligands
that bind to their own surface receptors,
modulating activity. Because growth hormone is
synthesized by the pituitary gland in the brain
and travels to the liver by the blood, growth
hormone signals via an endocrine mechanism.
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Chap. 15 Problem 3
Receptor 2 has greater affinity for the ligand
than Receptor 1 because the Kd for Receptor 2
(10-9 M) is lower than the Kd for Receptor 1
(10-7 M). The fraction of receptors that are
bound to the ligand when its concentration is
10-8 M can be calculated using the rearranged
form of the Kd equation, R/LR Kd/L. For
Receptor 1, R/LR (10-7 M)/(10-8 M) 10/1
at this concentration of ligand. The receptor
therefore is only about 10 saturated with
ligand. For Receptor 2, R/LR (10-9 M)/(10-8
M) 1/10 at this concentration of ligand. The
receptor therefore is about 90 saturated with
ligand.
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Chap. 15 Problem 6
The G protein cycle of activity in
hormone-stimulated G protein coupled receptor
(GPCR) regulation of effector proteins is
summarized in Fig. 15.17 (next slide). The
trimeric G protein complex is tethered to the
inner leaflet of the cytoplasmic membrane via
lipid anchors attached to the Ga and Gg subunits.
The trimeric GDP-bound form of the G protein is
inactive in signaling. The binding of a hormone
to the GPCR triggers a conformational change in
the receptor (Step 1) which promotes its binding
to the trimeric G protein (Step 2). Binding to
the activated GPCR triggers exchange of GTP for
GDP and activation of the Ga subunit which
dissociates from Gßg (Steps 3 4). Ga-GTP then
binds to the effector protein regulating its
activity (Step 5). In time (often lt 1 min), GTP
is hydrolyzed to GDP and Ga becomes inactive
(Step 6). It then recombines with Gßg. If a
mutation increased the GTPase activity of the G?
subunit, then the subunit would be active for a
shorter time than normal. The activation of the
downstream effector would therefore be reduced.
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Chap. 15 Problem 6 (continued)
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Chap. 15 Problem 10 (modified)
channels via G proteins. Describe the rhodopsin
signal transduction pathway.
The rhodopsin signal transduction pathway is
shown in Fig. 15.23. Light absorption by
rhodopsin triggers GTP/GDP exchange on the
transducin (Gat? subunit, and dissociation of
this trimeric G protein. Gat-GTP binds to and
activates a cGMP phosphodiesterase, reducing
intracellular cGMP level. This indirectly results
in the closing of non-selective Na/Ca2 ion
channels in the cytoplasmic membrane and
hyperpolarization of the membrane potential. This
results in decreased release of neurotransmitter
from the cell.
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Chap. 15 Problem 12
In the liver, muscle, and adipose tissue,
epinephrine raises cAMP levels through Gas-GTP
activation of adenylyl cyclase. The key target of
cAMP is protein kinase A (PKA) (Fig. 15.29a).
Through this point in the epinephrine-cAMP
pathway, the steps of signal transduction are the
same in all three tissues. However, each tissue
differs in the downstream targets of PKA,
resulting in cell type-specific responses.
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Chap. 15 Problem 15
Phospholipase C (PLC) cleaves the membrane lipid,
phosphatidylinositol 4,5-bisphosphate (PIP2) to
the second messengers, inositol
1,4,5-trisphosphate (IP3) and diacylglycerol
(DAG) (Fig. 15.35). The steps downstream of PLC
are illustrated in Fig. 15.36a. IP3 diffuses from
the cytoplasmic membrane to the ER where it binds
to and triggers the opening of IP3-gated Ca2
channels. The rise in cytoplasmic Ca2
activates calmodulin which in turn activates
certain cytoplasmic kinases, such as glycogen
phosphorylase kinase. DAG binds to and activates
the kinase known as protein kinase C (PKC). Cells
replenish ER calcium via ER membrane Ca2-ATPase
pumps that transport calcium back to the ER
lumen. These pumps also transport cytoplasmic
calcium outside of the cell. Extracellular
calcium is transported back into the cytoplasm by
activation of store-operated calcium channels in
the cytoplasmic membrane. This calcium ultimately
is transported back to the ER lumen by the ER
membrane Ca2-ATPase pumps (not shown).