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55 Cards in this Set
- Front
- Back
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Why do you get synergy between Insulin and prolactin? |
Due to the polyadenylation units at the end of the tail. They enhance the lifetime of the sequence -> more milk protein produced |
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What transcribes genes to mRNA? What is needed for initiation? Transcription start site usually follows what? |
-RNA Polymerase II - Many general and specific transcription factor proteins binding promoter -a TATA box |
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What increases transcription? What decreases transcription? |
-Activators binding enhancer DNA sequence -Repressors binding silencer DNA sequence |
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What do chromatin remodeling complexes do? |
- use ATP-driven conformational change to weaken histone-DNA interaction and DNA folding |
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What do histone acetylases do? What do histone deacetylases do? |
-add Ac groups to histones resulting in more DNA opening and transcription -remove Ac groups -> closes DNA conformation leading to less transcription -> both can be influenced by hormones |
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Steps of RNA processing? |
1. splice out introns 2. add 5' cap 3. add 3' poly-A tail 4. export mature mRNA through nuclear pores 5. Translate mRNA to protein until stop codon is reached |
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Complex which forms upon ribosome binding to mRNA? What displaces this? What then occurs? |
-Nascent chain associated complex (NAC) -Signal Recognition Particle, which docks with receptor on ER where translation continues along with cotranslational modifications |
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Final steps of protein synthesis? |
-Cleavage of SRP (preprohormone->prohormone) -folding by molecular chaperones -protein sent to golgi for modifications |
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What does hepcidin do? Important in? |
-Controls amount of Fe uptake in GI tract. -Important in red blood cell production -also important in immunology, as pathogens require iron to replicate -> hepcidin regulates white blood cell ability to keep iron away from pathogens |
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What does Brefeldin A do? What is used for? |
-Golgi inhibitor that prevents it from releasing protein products into extracellular spaces -used to see the build up/concentration of hormones and other products |
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What are the 3 types of coat proteins? Where are they used? |
COP I, COP II and clathrin |
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Function of COP I? |
Mediates retrograde transport of mature proteins which aren't being released from the golgi back to the ER |
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Function of COP II? |
Mediates transfer of vesicles from the RER to the cis-golgi |
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Function of Clathrin? |
Mediates the transfer of vesicles that bud from the trans-golgi and plasma membrane, then fuse with late endosomes |
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Vesicular secretion summary? |
1.Sorting of hormones 2.Coat protein association 3. budding and trafficking 4. uncoating 5. docking 6. fusing to target membrane |
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What influences the half life of mRNA? What things affect protein stability? |
-5' cap and length of 3' poly-A tail -post-translational modifications such as glycosylation, phosphorylation state, metabolic degradation, internalization etc |
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What do steroid hormones need to be modified by before secretion? |
Cytochrome P450 enzymes of SER -> produces lipid soluble products that are directly released at plasma membrane |
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What 2 things can be directly transported across plasma membrane? What 2 things must undergo vesicular fusion and exocytosis? |
-Steroids and eicosanoids -peptide hormones and NTs |
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What is the equilibrium dissociation constant of a hormone at a receptor equal to? |
Kd = K-1/K+1 = [H][R]/[HR] where K+1 = [H] + [R] --> [HR] and K-1 = opposite |
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What does Kd equal in a ligand saturation curve? Y axis = [HR] X axis = [H] |
the concentration of free H when 50% of R are bound |
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Shape of ligand saturation curve? |
Starts off linear, then starts to slow down as receptors are filled with hormone. Slowly flattens out to a max [HR] (R naught) |
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What is a Scatchard Plot? What does it tell you? |
a linear representation of a ligand saturation curve where Y axis = [HR]/[H] and X axis is [HR]. Shows you that Ro is at the X intercept and the slope is equal to (-1/Kd) IDEA: as [HR] the ratio of unbound to bound decreases |
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What is pindolol? What is iodocyanopindolol? What is it used for? |
-non-selecetive beta blocker - Radiolabeled pindolol: B1 adrenoreceptor and 5-HT1A receptor antagonist. Used in mapping hte distribution of beta adrenoreceptors in the body |
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5 types of cell surface receptors? |
1. 7 transmembrane domain GPCRs 2. Growth factor receptors (tyr kinase domain attached) 3. Cytokine receptors (tyr kinase separate) 4. Guanylyl cyclase receptors (cyclase attached) 5. novel cell surface receptors (ferroportin) |
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Structure of G protein coupled receptor? |
- 7 hydrophobic transmembrane domains spanning membrane - extracellular domain (N terminus, recognizes and binds to ligand) -cytoplasmic domain (C terminus, hydrophilic, transduce signal via G proteins) |
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Requirement for GPR diseases to cause loss of function? Why? For a GPR to cause constitutive activation? |
-Often need to be homozygous mutations to have loss of function as there is an excess of receptors - only a single point mutation needed |
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Structure of G proteins? |
-Heterotrimers, with alpha beta and gamma subunits. Alpha subunit has GTPase activity (cleaves GTP to GDP and Pi). Beta and Gamma act as a dimer |
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Three types of G protein alpha subunits? |
- Stimulatory (As): stimulate adenylyl cyclase - Inhibitory (Ai): inhibit adenylyl cyclase - Aq - stimulate phospholipase C |
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Steps of G protein signalling? |
-Ligand binds, inducing conformational change - Receptor-G protein complex forms -GDP dissociates from alpha subunit -GTP binds -Ga-GTP dissociates from receptor and beta/gamma subunits -Ga-GTP and beta/gamma act on effectors -alpha converts GTP to GDP -subunits reassociate |
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What two things regulate G protein signalling? |
1. GPR-associated protein (GAP) helps inactivate Ga-GTP and act as a scaffold for assembly 2. Receptor desensitization (B-adrenergic receptor kinase and arrestin) |
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3 effectors associated with stimulatory and inhibitory alpha subunits? |
-adenylyl cyclase -calcium channels -potassium channels |
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Effector associated with alpha q subunit? |
Phospholipase C beta |
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Main purposes of cAMP? |
-activation of protein kinases -regulates the passage of calcium through ion channels (second messenger) |
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GA(s)-adenylyl cyclase coupled signalling steps? |
1. Epinephrine binds B-adrenergic receptor with GA(s) 2. Adenylyl cyclase activated ti produce cAMP from ATP 3. cAMP binds to inhibitory subunit of PKA and releases enzyme 4. PKA phosphorylates substrates 5. cAMP response element binding protein (CREB) binds consensus CRE in basal state, but when phosphorylated, is activated to enhance transcription of a gene |
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Common 2nd messenger? Where is it found? What does it do? What hydrolyzes it? |
-Phosphatidylinositol (4,5)-bisphosphate (PIP2) - component of cell membranes -important substrate for a number of important signalling events -Phospholipase C |
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GA(q)-PLC-coupled signalling steps? |
1. Ligand (ex angiotensin II) binds receptor with GA(q) 2. Phospholipase cleavage of PIP2 to IP3 causing release of Ca to cytoplasm from ER and formation of DAG 3. Ca activates protein kinases, promotes secretion, causing contraction (DAG activates PKC) 4. PKC phosphorylates numerous substrates, some of which involve transcription effects in the nucleus |
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What two things make upactivation protein 1? |
C-jun and c-fos |
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What two things does angiotensin have effects on? |
Immune system and cell growth |
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Steps for desensitization of the B-adrenergic receptor in G protein signalling? |
1. Activation of receptor and AC upon ligand binding 2. Phosphorylation of receptor by B-adrenergic receptor kinase (BARK) 3. Inactive AC; arrestin binds when phosphorylated and blocks association with G proteins 4. Phosphatase removes phosphate from receptor, allows G protein association and activation of AC |
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What does cholera toxin do? |
ADP ribosylation of GA(s) - blocks GTPase activity of alpha(s) subunit, keeping AC active longer. Increases water and salt secretion in gut: diarrhea |
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What does pertussis toxin do? |
ADP ribosylation of GA(i) and GA(o), prevents G protein from binding hormone receptor - inactive GDP-bound protein |
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Growth factor receptors domains and functions? |
Binding domain, transmembrane domain, tyrosine kinase domain: - adds Phos to substrates that recruit other proteins = signalling complex, - and adds phos to proteins that are also kinases = phos cascades |
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Steps of growth factor receptor signaling complexes? |
1. Dimers form upon ligand binding 2. autophosphorylation 3. recruitment of accessory proteins, SH2 and SH3 4. SH3 tyrosine is phosphorylated 5. Very large complexes form with complicated signaling |
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What do SH2 domains recognize? What do SH3 domains recognize? What do SH3 domains also have? |
-phosphorylated tyrosines - proline rich sequences -tyrosine phosphorylation |
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Important phosphorylation pathway involving growth factors? |
MAPK pathway: mitogen activated protein kinase pathway |
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Cytokine receptors domains? What are they receptors for? |
-Binding domain, transmembrane domain, accessory protwin with tyrosine kinase domain (enzyme not a part of receptor, but gets recruited) -cytokines, erythropoietin, colony-stimulating factor, PRL, and GH |
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Specifics of growth hormone signalling? |
- 2GH receptors brought together by GH: signals recruitment of JAK2 (a tyrosine kinase) -JAK2 phosphorylates GHR, providing a docking site for STATs (DNA regulatory elements involved in control of GH targets) |
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What does STAT stand for? |
Signal Transducers and Activators of Transcription |
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Guanylyl cyclase receptor domains? What does kinase-like domain do? What happens when the ligand binds? |
-binding domain, transmembrane domain, kinase-like domain -regulates catalytic domain of guanylyl cyclase - conformational change removes inhibitory control of cyclase |
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Example of a guanylyl cyclase receptor and function? |
Atrial natriuretic peptide (ANP): role in hypertension as it is a powerful vasodilator |
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Two major GC linked receptor classes? |
Soluble and membrane-bound |
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Steps for soluble guanylyl cyclase signaling? (eNOS) |
-Ach/bradykinin binds GPCR-GA(q) receptors which triggers influx of Ca+2 which activates eNOS -eNOS converts O2 to NO, which stimulates soluble GC -Soluble GC converts GTP to cGMP, which activates PKG, promoting vasodilation |
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Steps for soluble guanylyl cyclase signaling? (iNOS) What is able to downregulate this? |
iNOS is found in inflammatory cells of immune system. Cytokines bind to cytokine receptor, activating iNOS -iNOS function the same as eNOS to stimulate PKG and vasodilation. -Steroids downregulate the stimulation of iNOS |
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What is hepcidin? When is it released? |
-A polypeptide hormone that controls Fe levels -It is released form the liver when high Fe levels and there is inflammation |
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How does the body control Fe release from the gut, liver and WBCs? |
Hepcidin binds to ferroportin, causing phosphorylation by JAK 2. It is then ubiquinated and degraded, downregulating ferroportin, shuttling iron out of the cell |
