Term
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Definition
| secreted molecules that coordinate the aggregation of free-living cells for sexual mating or differentiation under certain environmental conditions |
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Definition
| other extracellular signaling molecules that function within an organism to control a variety of processes |
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Definition
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Definition
| signals, binds to a structurally complementary site on the extracellular or membrane-spanning domains of the receptor |
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Definition
| intracellular proteins or small molecules that carry the signal to one or more effector proteins |
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Definition
| overall process of converting extracellular signals into intracellular responses |
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Term
| G protein couple receptors |
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Definition
| consist of an integral membrane receptor protein coupled to an intracellular G proteins that transmits signals to the interior of the cell |
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Term
| Describe the overall process of cell signaling involving cell-surface receptors |
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Definition
1. Synthesis of the signaling molecule by signaling cell and its incorporation into small intracellular vesicles
2. Release into the extracellular space by exocytosis
3. Transport of the signal to the target cell
4. Binding of the signaling molecule to a specific cell-surface receptor triggers a conformational change
5. Activated receptor activates one or more downstream signal transduction proteins or small-molecule second messengers
6. Activation of effector proteins |
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Term
| Describe G-protein coupled receptors – what is the receptor |
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Definition
| Consist of an integral membrane protein receptor |
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Term
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Definition
| Intracellular protein that transmits signals to the interior of the cell |
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Term
| Describe the basic structural and functional properties of a G-protein coupled receptor |
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Definition
| In its “on” state it is bound to GTP, the two domains are bound to the GTP, and the protein can interact with other proteins. In its “off” state is it bound to GDP, and the domains are relaxed, the protein is unable to bind effector proteins |
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Term
| Name four cellular processes which are regulated by G protein-coupled receptor pathways. |
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Definition
| Visual, olfactory, gustatory and neurotransmitter |
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Term
| List the two major types of cellular responses which binding of signaling molecules elicits |
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Definition
| Changes in the activity or function of specific enzymes and other proteins that preexist in the cell or changes in the amounts of specific proteins produced by a cell, most commonly by modification of transcription factors that stimulate or repress gene expression |
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Term
| What is meant by the phrase “signal transduction pathway” |
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Definition
| Refers to the connection between an activated receptor and a cellular response via several intermediates |
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Term
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Definition
the signaling molecules are synthesized and secreted by signaling cells, transported through the circulatory system of the organism and finally act on target cells distant from their site of synthesis
Examples: Hormones |
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Definition
the signaling molecules released by a cell affect only those target cells in close proximity
Example: neurotransmitters |
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Definition
cells respond to substances that they themselves release
example: growth factors |
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Term
| Name a class of molecules which are frequently the signals in autocrine signaling |
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Definition
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| Explain what is meant by “hormone binding through molecular complementary”. |
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Definition
| Interactions between the surfaces of the receptor and the ligand that make them specific to each other |
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Term
| How does molecular complmentary contribute to specificity of signaling in different tissues |
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Definition
| Binding of a particular ligand to the receptor triggers a different response in each type of cell |
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Term
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Definition
| add phosphate groups to specific residues of specific target proteins |
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Term
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Definition
| remove phosphate groups from specific residues on target proteins |
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Term
| What type of biomolecule do kinase and phosphatase enzymes act upon? |
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Definition
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Term
| Describe the role which protein kinases and phosphatases play in cell signaling. |
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Definition
| Common cellular mechanism for regulating proteins activity |
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Term
| Can a protein be a substrate for more than one kinase? |
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Definition
| Many proteins are substrates for multiple kinases |
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Term
| Name the two major classes of kinases and describe on what basis the classification is made. |
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Definition
| those that add phosphate to the hydroxol group on a serine or threonine residue |
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Term
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Definition
| exist in two forms (1) active and (2) inactive |
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Term
| What role does GEF protein play in GTP switches? |
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Definition
| Catalyze the dissociation of the bound GDP and its replacement by GTP |
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Term
| Describe the general mechanism of GTP-switch proteins |
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Definition
| Conversion of active to inactive by hydrolysis of GTP is accelerated by GAPs, reactivation is promoted by GEFs which catalyze the dissociation of GDP and its replacement by GTP |
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Term
| Name the two major classes of GTP switch proteins |
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Definition
| Trimeric G-proteins and monomeric G-proteins |
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Term
| Name four common intracellular second messengers |
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Definition
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Term
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Definition
| activation of one proteins leads to the activation of another |
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Definition
| a single receptor can activate multiple G proteins, each of which in turn activate an effector protein |
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Term
| Describe how Ca2+ acts as a second messenger |
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Definition
| Free Ca2+ is kept low in the Cytosol via ATP-powered pumps, a signal-induced release of Ca2+ can increase its levels |
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Term
| Where is intracellular Ca2+ stored? |
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Definition
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Term
| What protein works in concert with Ca2+ in cell signaling? |
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Definition
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Term
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Definition
| Activation of Adenylyl cyclase molecules via epinephrine |
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Term
| What enzyme is required for the generation of cAMP? |
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Definition
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Term
| What protein does cAMP activate? |
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Definition
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Term
| How does this play a role in the “signaling cascade"? |
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Definition
| Protein kinase A activated the target enzyme which makes the desired product |
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Term
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Definition
| Measure of the affinity of the receptor for its ligand |
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Term
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Definition
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Term
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Definition
| mimic the function of a natural hormone by binding to its receptors and inducing the normal response |
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Term
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Definition
| bind to the receptor but induce no response |
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Term
| Describe how TNFalpha agonists’ drugs work |
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Definition
| The drug binds tightly to free TNF alpha and prevent it from binding to its cell-surface receptors and causing inflammation |
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Term
| Name two laboratory based methods for determining the specificity and affinity of ligands for their receptors |
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Definition
| Competition assay and direct binding assays |
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Term
| Describe the mechanism of action of the asthma drug Alprenolol |
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Definition
| Antagonist of the beta adrenergic receptors, they are used to slow heart contractions in the treatment of cardiac arrhythmias and angina |
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Term
| Describe the role of EGF receptor number in the treatment of breast cancer |
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Definition
| Some monoclonal antibodies bind to specific EGF receptors and block the signal which stops the inappropriate growth stimulated by EGF |
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Term
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Definition
| A particular EGF receptor that is elevated in some breast cancers |
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Term
| By what mechanisms are receptor numbers down-regulated in the cell? |
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Definition
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Term
| Describe the four common elements of G-protein coupled receptor (GPCR) signal transduction pathways |
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Definition
1. A receptor that contains seven membrane spanning alpha helixes
2. A couple trimeric G protein which function as a switch by cycling between active and inactive forms
3. A membrane-bound effector protein
4. Proteins that participate in feedback regulation and desensitization of the signaling pathway |
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Term
| Describe the basic structure common to all GPCRs |
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Definition
| Same orientation in the membrane and 7 Transmembrane alpha helixes, four extracellular segments and four cytoplasmic segments, N terminus is on the exoplasmic face, C terminus is on the cytoplasmic face |
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Term
| Give an example of a well characterized GPCR |
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Definition
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Term
| Which types of G alpha subunits activate adenylate cyclase? |
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Definition
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Term
| Which types of G alpha subunits activate Phospholipase C? |
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Definition
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Term
| Which types of G alpha subunits activate cGMP phosphodiesterase? |
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Definition
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Term
| Which effector generates cAMP? |
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Definition
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Term
| Which effector generates IP3 and DAG? |
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Definition
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Term
| Molecular Basis of Cholera |
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Definition
| The toxin causes the G alpha S remains in its active state, continuously activating Adenylyl cyclase in the absence of hormonal stimulation. The resulting rise in cAMP leads to the loss of electrolytes and water into the intestinal lumen which causes diarrhea characteristic of cholera |
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Term
| Molecular basis of bordetella |
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Definition
| Bordetella toxin catalyzes a modification of G alpha I that prevents release of bound GDP and G alpha I is locked in its inactive state, reducing inhibition of Adenylyl cyclase causes increase in cAMP in epithelial cells and promotes loss of fluids and electrolytes in mucus secretion |
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Term
| Describe the mechanism of action of Muscarinic acetylcholine receptors in relation to GPCR |
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Definition
| Binding of acetylcholine trigger activation of the G alpha I subunit and its dissociation from the G beta gamma subunit. The G beta gamma subunit binds to and opens the associated effector protein, a K+ channel. |
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Term
| How does the mechanism of action of Muscarinic aceytlcholine regulate cardiac muscle contraction? |
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Definition
| The increase in K+ permeability hyperpolarizes the membrane which reduces the frequency at which the heart muscle contracts |
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Term
| Describe the mechanism of action of Rhodopsin in the visual transduction cycle in relation to GPCR |
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Definition
| Light activates rhodopsin which binds to inactive ADP-bound G alpha t protein and mediates the replacement of GDP with GTP. The free G alpha t-GTP generated then activated cGMP phosphodiesterase by binding its inhibitory gamma subunits and dissociated them from the catalytic alpha and beta subunits which hydrolyze cGMP to GMP. The decrease in cytosolic cGMP leads to dissociation of cGMP from the nucleotide-gated channels in the plasma membrane closing them. The membrane becomes hyperpolarized and neurotransmitter is released. |
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Term
| How does the mechanism of action of Rhodopsin lead to the perception of light? |
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Definition
| release of neurotransmitter |
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Term
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Definition
| closes the cation channels in rod-cell plasma membrane via large concentration |
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Term
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Definition
| trimeric G protein couples to rhodopsin, contains a G alpha unit |
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Term
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Definition
| binds to three phosphorylated serine residues on the C-terminal opsin segment, prevents interaction of G alpha t subunit with phosphorylated active rhodopsin |
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Term
| Describe how GPCR/cAMP regulates the breakdown of glycogen |
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Definition
When levels of cAMP are high this activated protein kinase A, which inhibits glycogen synthesis and promotes glycogen degradation via protein kinase cascade
When levels of cAMP are low PKA is inactivated, which promotes glycogen synthesis and inhibits glycogen degradation |
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Term
| Describe the mechanism of cAMP activation of protein kinase A by releasing inhibitory subunits. |
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Definition
| cAMP can activate or inactive PKA, if it activated PKA then PKA phosphorylated an inhibitor of phosphoprotein phosphatase (PP), this prevents the phosphatases from dephosphorylating the activated enzymes in the cascade. When PKA is inactivated it releases the active form of PP |
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Term
| Describe the role of epinephrine in glycogen metabolism. |
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Definition
| Epinephrine stimulates activation of Adenylyl cyclase which produces cAMP |
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Term
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Definition
| in the adrenal cortex activated cAMP/PKA which causes an increases in synthesis of aldosterone and cortisol |
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Term
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Definition
| in the thyroid gland activates cAMP/PKA which causes secretion of thyroxine |
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Term
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Definition
| in the bone activates cAMP/PKA which causes increase in resoprtion of calcium from bone |
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Term
| Describe the role of CREB in activation of transcription |
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Definition
| Phosphorylated CREB binds to CRE containing target genes and also binds to a co-activator which stimulates gene transcription |
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Term
| Explain how anchoring proteins localized the effects of cAMP to specific regions of the cell. |
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Definition
| Family of anchoring proteins localizes isoforms of PKA to specific subcellular locations thereby restricting cAMP-dependent response to these locations |
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Term
| Describe the mechanisms of GPCR/cAMP/PKA pathway down regulation |
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Definition
(1) the affinity of the receptor for its ligand decreases when the GDP bound to G alpha subunit s is replaced with GTP
(2) the intrinsic GTPase activity of G alpha s that converts the bound GTP to GDP is enhanced when G alpha s binds to adenylyl cyclase
(3) cAMP phosphodiesterase acts to hydrolyze cAMP to 5’AMP terminating the cellular response |
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Term
| Describe how Ca2+ plays a role in the blood clotting cascade |
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Definition
| Thrombin binding triggers a rise in cytosolic Ca2+, that in turn causes a conformational change in the platelets that leads to their aggregation |
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Term
| Provide examples of hormones which lead to increases in intracellular Ca2+ levels |
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Definition
| Acetylcholine, vasopressin, thrombin, antigen, and peptide growth factors |
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Term
| State the tissues in which hormones that increase intracellular Ca2+ levels act. |
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Definition
Acetylcholine acts in the parotid and vascular or stomach smooth muscle
Vasopressin acts in the liver
Thrombin acts in the blood platelets
Antigen acts in the mast cells
Peptide growth factors act in fibroblasts |
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Term
| Provide a detailed explanation of the two key second messengers generated by Phospholipase C |
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Definition
| PIP2 is cleaved by Phospholipase C into DAG and IP3 which can freely diffuse in the Cytosol |
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Term
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Definition
| a multipurpose switch protein that mediates many cellular effects of Ca2+ ions |
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Term
| Which type of kinase does Calmodulin activate? |
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Definition
| Kinases that phosphorylate transcription factors |
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Term
| Describe the mechanism of action of Nitroglycerin in the treatment of angina |
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Definition
| NO causes the relaxation of smooth muscles cells surround the blood vessels that feed the heart muscle, which increasing the diameter of the blood vessels and increases the flow of oxygen bearing blood to the heart |
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Term
| How does the mechanism of action of nitroglycerin relate to Ca2+ signaling? |
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Definition
| after Ca2+ binds Calmodulin it activated the activity of NO synthase |
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Term
| Describe the role of Ca2+ signaling in glycogenolysis. |
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Definition
| Rise of Ca2+ in the Cytosol activates glycogen phosphorylase kinase which stimulates the degradation of glycogen to glucose-1-phosphate |
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Term
| In paracrine signaling, the signaling molecule |
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Definition
| acts on cells in close proximity to the secreting cell. |
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Term
| GTPases serve in many signal transduction pathways and the presence of GTP or GDP dictates where the pathway is on or off, respectively. Which of the following statements is true regarding guanine nucleotide exchange factors (GEF) and the role in these signaling pathways? |
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Definition
| They catalyze the dissociation of GDP on the G-protein and promote the replacement of GTP |
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Term
| Cell sensitivity to an external signal is determined by |
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Definition
| the number of surface receptors. |
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Term
| If [R] = the free receptor concentration and [L] = the free ligand concentration, Kd is |
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Definition
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Term
| In trimeric G proteins, GTP binds to |
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Definition
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Term
| Which of the following is not a common intracellular second messenger? |
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Definition
| adenosine triphosphate (ATP) |
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Term
| Phospholipase C is activated by |
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Definition
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Term
| Which of the following general statement(s) about a G protein-coupled receptor is (are) true? |
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Definition
| It is organized with the C-terminus on the cytoplasmic face of the membrane. |
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Term
| All the following statement(s) about cholera toxin are true except: |
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Definition
| It is a G protein-coupled receptor. |
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Term
| Phosphatidylinositol 4,5-bisphosphate (PIP2) is cleaved by phospholipase C into |
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Definition
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Term
| 1,2-diacylglycerol (DAG) and inositol 1,4,5-trisphosphate (IP3) are cleaved from phosphatidylinositol 4,5-bisphosphate (PIP2) by the enzyme |
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Definition
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Term
| cGMP phosphodiesterase catalyzes the conversion of |
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Definition
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Term
| Which enzyme plays a role in regulating rhodopsin-induced closing of cation channels? |
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Definition
| Guanylyl Cyclase and Phosphodiesterase |
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Term
| Which of the following is a common step in the opening/closing of ion channels by acetylcholine and rhodopsin binding to their receptors? |
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Definition
| The G-alpha GTP subunit dissociates from the G-beta-gamma complex. |
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Term
| Rhodopsin, a light-sensitive GPCR whose role in vision is dependent on its phosphorylation status, is influenced in part by the protein arrestin. Which of the following is true in regards to rhodopsin and vision? |
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Definition
| Arrestin binds to the completely phosphorylated opsin to inhibit signaling. |
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Term
| Which of the following statement(s) about adenylyl cyclase stimulation/inhibition in adipose cells is (are) true? |
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Definition
| Epinephrine stimulates adenylyl cyclase. |
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Term
| Which of the following events occur(s) during the epinephrine-stimulated conversion of glycogen to glucose-1-phosphate? |
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Definition
| activation of PKA by cAMP, inhibition of glycogen synthase, and activation of glycogen phosphorylase |
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Term
| The activity of beta-adrenergic receptors is regulated by |
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Definition
| beta-adrenergic receptor kinase (BARK). |
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Term
| Which of the following mechanisms can terminate the intracellular signaling pathway once the concentration of the external signal decreases? |
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Definition
| degradation of the second messanger, desensitization of receptors, deactivation of a signal tranduction protein |
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Term
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Definition
| is a ubiquitous protein in eukaryotic cells, and binds Ca2+ in a cooperative fashion |
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Term
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Definition
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Term
| 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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Definition
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Term
| 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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Definition
| Fusion of intracellular vesicles containing GLUT4 glucose transporters with the plasma membrane, stimulation of the conversion of glucose to glycogen and inhibition of glucose synthesis from smaller molecules |
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