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30 Cards in this Set
- Front
- Back
In paracrine signaling, the signaling molecule
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acts on cells in close proximity to the secreting cell.
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Cell sensitivity to an external signal is determined by
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the number of surface receptors.
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If [R] = the free receptor concentration and [L] = the free ligand concentration, Kd is
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[R][L]/[RL]
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In trimeric G proteins, GTP binds to
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the a subunit
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common intracellular second messenger
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inositol 1,4,5-trisphosphate (IP3)
1,2 diacylglycerol (DAG) 3´-5´ cyclic guanine monophosphate (cGMP) |
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Phospholipase C is activated by
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Gaq
Gao |
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G protein–coupled receptor is
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It contains seven transmembrane domains
It is organized with the C-terminus on the cytoplasmic face of the membrane |
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cholera toxin are
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It chemically modifies the Gas protein
It prevents hydrolysis of bound GTP to GDP It leads to continuous activation of adenylyl cyclase |
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cGMP phosphodiesterase catalyzes the conversion of
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cGMP to 5´-GMP
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Which enzymes plays a role in regulating rhodopsin-induced closing of cation channels
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guanylyl cyclase
phosphodiesterase |
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what following is a common step in the opening/closing of ion channels by acetylcholine and rhodopsin binding to their receptors
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The Ga•GTP subunit dissociates from the Gby complex
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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. |
Epinephrine stimulates adenylyl cyclase
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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 |
activation of PKA by cAMP
inhibition of glycogen synthase activation of glycogen phosphorylase |
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The activity of B-adrenergic receptors is regulated by
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B-adrenergic receptor kinase (BARK).
clathrin B-arrestin. |
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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 |
degradation of the second messenger
desensitization of receptors deactivation of a signal transduction protein |
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Phosphatidylinositol 4,5-bisphosphate (PIP2) is cleaved by phospholipase C into
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1,2-diacylglycerol (DAG)
inositol 1,4,5-trisphosphate (IP3). |
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Calmodulin is a
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ubiquitous protein in eukaryotic cells.
binds Ca2+ in a cooperative fashion. |
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DAG activates
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PKC
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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
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elevated cytosolic Ca2+.
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After a meal, when blood glucose rises, circulating insulin binds to insulin receptors on various cell types and reduces blood glucose levels by
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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. |
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Explain the differences between endocrine, paracrine, and autocrine signaling
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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.
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Describe the differences between an agonist and an antagonist.
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: 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.
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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?
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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.
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What experimental approach was used to identify functional domains of G protein–coupled receptors?
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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.
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Summarize the steps in the cycling of GTPase switch proteins from active to inactive states.
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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.
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Describe the proposed mechanism for the opening of K+ channels by cardiac muscarinic acetylcholine receptors.
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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.
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Describe the experimental evidence that the intrinsic GTPase activity for the G subunit is important for terminating effector activation.
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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.
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Describe the steps in the synthesis of 1,2-diacylglycerol (DAG) and inositol 1,4,5-trisphosphate (IP3) from phosphatidylinositol (PI).
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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).
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How does the body respond to decreases in blood glucose levels below about 5 mM
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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
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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”?
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: 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
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