Chapter 15

Front 1

In paracrine signaling, the signaling molecule

Back 1

acts on cells in close proximity to the secreting cell.

Front 2

Cell sensitivity to an external signal is determined by

Back 2

the number of surface receptors.

Front 3

If [R] = the free receptor concentration and [L] = the free ligand concentration, Kd is

Back 3

[R][L]/[RL]

Front 4

In trimeric G proteins, GTP binds to

Back 4

the a subunit

Front 5

common intracellular second messenger

Back 5

inositol 1,4,5-trisphosphate (IP3)

1,2 diacylglycerol (DAG)

3´-5´ cyclic guanine monophosphate (cGMP)

Front 6

Phospholipase C is activated by

Back 6

Gaq
Gao

Front 7

G protein–coupled receptor is

Back 7

It contains seven transmembrane domains

It is organized with the C-terminus on the cytoplasmic face of the membrane

Front 8

cholera toxin are

Back 8

It chemically modifies the Gas protein

It prevents hydrolysis of bound GTP to GDP

It leads to continuous activation of adenylyl cyclase

Front 9

cGMP phosphodiesterase catalyzes the conversion of

Back 9

cGMP to 5´-GMP

Front 10

Which enzymes plays a role in regulating rhodopsin-induced closing of cation channels

Back 10

guanylyl cyclase

phosphodiesterase

Front 11

what following is a common step in the opening/closing of ion channels by acetylcholine and rhodopsin binding to their receptors

Back 11

The Ga•GTP subunit dissociates from the Gby complex

Front 12

Which of the following statement(s) about adenylyl cyclase stimulation/inhibition in adipose cells is (are) true?
a. Prostaglandin E1 stimulates adenylyl cyclase.
b. Glucagon inhibits adenylyl cyclase.
c. Epinephrine stimulates adenylyl cyclase.

Back 12

Epinephrine stimulates adenylyl cyclase

Front 13

Which of the following events occur(s) during the epinephrine-stimulated conversion of glycogen to glucose-1-phosphate?
a. activation of PKA by cAMP
b. inhibition of glycogen synthase
c. activation of glycogen phosphorylase
d. b and c
e. all of the above

Back 13

activation of PKA by cAMP

inhibition of glycogen synthase

activation of glycogen phosphorylase

Front 14

The activity of B-adrenergic receptors is regulated by

Back 14

B-adrenergic receptor kinase (BARK).

clathrin

B-arrestin.

Front 15

Which of the following mechanisms can terminate the intracellular signaling pathway once the concentration of the external signal decreases?
a. degradation of the second messenger
b. desensitization of receptors
c. deactivation of a signal transduction protein
d. a and b
e. all of the above

Back 15

degradation of the second messenger

desensitization of receptors

deactivation of a signal transduction protein

Front 16

Phosphatidylinositol 4,5-bisphosphate (PIP2) is cleaved by phospholipase C into

Back 16

1,2-diacylglycerol (DAG)

inositol 1,4,5-trisphosphate (IP3).

Front 17

Calmodulin is a

Back 17

ubiquitous protein in eukaryotic cells.


binds Ca2+ in a cooperative fashion.

Front 18

DAG activates

Back 18

PKC

Front 19

In muscle, glycogen phosphorylase kinase can be activated by nerve stimulation even in the absence of hormonal signals. Nerve stimulation alone results in activation of glycogen phosphorylase kinase as a result of

Back 19

elevated cytosolic Ca2+.

Front 20

After a meal, when blood glucose rises, circulating insulin binds to insulin receptors on various cell types and reduces blood glucose levels by

Back 20

fusion of intracellular vesicles containing GLUT4 glucose transporters with the plasma membrane.

stimulation of the conversion of glucose to glycogen.

inhibition of glucose synthesis from smaller molecules.

Front 21

Explain the differences between endocrine, paracrine, and autocrine signaling

Back 21

In endocrine signaling, signaling molecules are synthesized by one organ and act on distant target cells. In animals the signaling molecule is carried to target cells by the blood or other extracellular fluids. In paracrine signaling, the signaling molecules are released and affect only target cells in close proximity. In autocrine signaling, the cell that releases the signaling molecule is also affected by the released signaling molecule.

Front 22

Describe the differences between an agonist and an antagonist.

Back 22

: Agonists are molecules that mimic the function of a natural ligand by binding to the receptor and inducing the normal response. In contrast, an antagonist binds to the receptor but does not induce a response. An antagonist can block the binding of the natural ligand, thus reducing the normal physiological response to the ligand.

Front 23

A particular antagonist for an epinephrine-receptor protein is under consideration as a new drug. What values would you use to measure how tightly the drug binds to the target protein compared to the tightness of epinephrine binding? What technique might you use to measure drug binding?

Back 23

The dissociation constant, Kd, is a measure of how tightly a ligand binds to its receptor. If Kd is less, that would mean the antagonist binds more tightly to the receptor protein than epinephrine binds. You could use a competitive binding assay to measure drug binding.

Front 24

What experimental approach was used to identify functional domains of G protein–coupled receptors?

Back 24

The functional domains of G protein–coupled receptors were determined by experiments using recombinant chimeric receptor proteins containing parts of the a2 and B2 adrenergic receptors. These chimeric receptors were tested for their ligand-binding specificity and their ability to activate or inhibit adenylyl cyclase. The results of these studies demonstrated that the cytosolic loop (C3 loop) between a helices 5 and 6 interacts with G proteins.

Front 25

Summarize the steps in the cycling of GTPase switch proteins from active to inactive states.

Back 25

GTPase switch proteins cycle from inactive to active states depending upon whether GTP (active) or GDP (inactive) is bound. Signal-induced receptor activation leads to the conversion of the GTPase switch protein from an inactive to an active state mediated by a guanine nucleotide exchange factor (GEF). GDP is released and replaced by GTP, resulting in a conformational change that allows the protein to activate downstream effector proteins. The intrinsic GTPase activity causes hydrolysis of GTP to GDP and the conversion back to the inactive state.

Front 26

Describe the proposed mechanism for the opening of K+ channels by cardiac muscarinic acetylcholine receptors.

Back 26

Cardiac muscarinic acetylcholine receptors are linked to K+ channels by a trimeric G protein. Binding of acetylcholine to its receptor triggers the activation and release of the Gia-GTP subunit from the Gby subunit. The released Gby subunit, rather than the Gia subunit then binds to and opens the K+ channel. Activation is terminated by the hydrolysis of GTP to GDP and the reformation of the ternary complex.

Front 27

Describe the experimental evidence that the intrinsic GTPase activity for the G subunit is important for terminating effector activation.

Back 27

The role of the intrinsic GTPase of the Ga subunit has been investigated using GTP analogs that can bind to the Ga subunit but cannot be hydrolyzed by the intrinsic GTPases. In these nonhydrolyzable compounds, the terminal phosphodiester (P–O–P) bond in GTP is replaced with P–CH2–P or P–NH–P bonds. In the presence of these nonhydrolyzable GTPs, the response of the effector protein is prolonged upon ligand-induced activation of the receptor. This is because the displacement of GDP with the modified GTP results in continuous activation of the effector protein. Because the bound GTP analog cannot be hydrolyzed to GDP, the effector remains in an active state permanently.

Front 28

Describe the steps in the synthesis of 1,2-diacylglycerol (DAG) and inositol 1,4,5-trisphosphate (IP3) from phosphatidylinositol (PI).

Back 28

Phosphatidylinositol (PI) is phosphorylated to form PI 4-phosphate (PIP), which is in turn phosphorylated to form PI 4,5-bisphosphate (PIP2). PIP2 is a substrate for phospholipase C, which cleaves PIP2 to 1,2-diacylglycerol (DAG) and inositol 1,4,5-trisphosphate (IP3).

Front 29

How does the body respond to decreases in blood glucose levels below about 5 mM

Back 29

Reduced insulin secretion induces a cells in the pancreas to release glucagon into the blood. Glucagon binds to the glucagon receptor in liver cell membranes. The glucagon receptor is coupled to a Gas protein. Stimulation of the glucagon signal pathway in liver cells activates PKA. The overall effect is to inhibit glycogen synthesis and increase glycogenolysis. Glycogen breakdown yields glucose 1-phosphate which liver cells convert to glucose. Glucose is released into the blood, bringing the blood glucose level back up to normal

Front 30

Currently, there are about 150 G protein–coupled receptor proteins whose ligands and functions are unknown. What research approaches have been used to discover the signaling molecules associated with these “orphan GPCR’s”?

Back 30

: One approach is to express the receptor genes in transfected cells. The transfected cells are used to determine if any ligand substances in tissue extracts can activate signal transduction pathways in these cells