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8. signal transduction, g-proteins
BrownMed
30
Accounting
Pre-School
10/31/2010

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Term
glycogenolysis results from
Definition
activation of glycogen phosphorylase in response to catecholamines (external cell stimulus - epi)
Term
cAMP is synthesized from
Definition
Mg2+-ATP by adenylyl cyclase. 2 terminal phosphates are removed, generating pyrophosphate. a link is formed between 5'hydroxymethyl group and 3'phosphate, hence 3'5'cAMP.
Term
cAMP is degraded by
Definition
hydrolysis, catalyzed by phosphodiesterases (which may be hormone sensitive - for instance, activated by insulin). process yields AMP.
Term
cAMP synthesis/degradation reversible?
Definition
yes to both, but for both the forward reaction is favored greatly.
Term
G-protein (4)
Definition
interacts with beta-adrenergic receptor, causing it to dissociate from its ligand, epi. binds gtp (nucleotide exchange of gdp for gtp, which is then hydrolyzable). activates adenylate cyclase, dependent on gtp. turns itself off by hydrolyzing gtp.
Term
signal transducer
Definition
G-protein
Term
non-hydrolyzable GTP analogues
Definition
very potent activators of adenylyl cyclase
Term
heterotrimeric g-protein
Definition
alpha, beta and gamma subunits
Term
alpha subunit of g protein (2)
Definition
Gs alpha and Gi alpha: stimulate/inhibit adenylate cyclase
Term
Gs alpha cycle
Definition
receptor binds hormone, GDP bound by alpha is replaced by GTP, GTP-bound alpha releases from beta-gamma and activates an effector, alpha hydrolyzes the GTP (returning it to the GDP-bound state)
Term
heterotrimeric G proteins relay signals from ____ receptors
Definition
over 1000
Term
cholera toxin
Definition
catalyzes the ADP-ribosylation of Gs alpha, which inhibits GTPase acitivity in gut lumen (never gets into the blood stream); = always on. NAD+ is the ADP donor.
Term
pertussis
Definition
lymphocytosis, impaired cilia function in lungs and hypoglycemia + cough. pertussis toxin catalyzes adp-ribosylation of Gi alpha via NAD+ donor. blocks Gi alpha's ability to exchange GDP for GTP, so the subunit doesn't work and there's no inhibition of adenylate cyclase = always on. systemic.
Term
rhodopsin-transducin system / toxic effects
Definition
rhodopsin (receptor in rods in the retina) "captures" a photon, causing isomerization. transducin is the g-protein (t-alpha subunit!!!). nucleotide exchange > alpha subunit dissociates >>> phosphodiesterase is the effector; it hydrolyzes cGMP. sodium channels close due to low levels of cGMP. hyperpolarization = vision. TRANSDUCIN IS A SUBSTRATE FOR CTX and PTX.
Term
Golf
Definition
activated by chemoreceptors in the cribiform plate. cAMP > opening of sodium channel
Term
adenylate cyclase is activated how
Definition
INdirectly by hormones/GTP; directly by forming a complex with Gs alpha.
Term
biological actions of cAMP are mediated by
Definition
PKA (cAMP dependent protein kinase)
Term
PKA / how does it work
Definition
serine/threonine kinase. inactive form is heterotetramer: R2-C2. R = regulatory, binds cAMP. C = catalytic kinase, catalyzes ATP > ADP + protein-P. /// 2 Rs form a complex with cAMP, leaving the Cs and activating them.
Term
while bound to R, cAMP is ____ from ____. dissociation of cAMP from R is ____
Definition
protected from hydrolysis. readily reversible.
Term
PKA can phosphorylate and regulate
Definition
enzymes, receptors, ion channels, transporters and transcription factors. FBPase2, phosphorylase kinase, acetyl coa carboxylase
Term
CREB
Definition
cAMP response element binding protein; contains 4 leucine zipper regions.
Term
phosphorylation by PKA in response to cAMP activates
Definition
DNA binding
Term
ras proto-oncogene (4)
Definition
60% same between yeast and humans. one of the "small G-proteins". activation of GAP induces GTPase activity (the off switch). mutations in ras most often cause loss of GTPase activity in growth hormone receptors- lung, colon, pancreas cancers
Term
GAP
Definition
GTPase Activating Protein in ras
Term
altered g-protein signaling is involved in ... (3)
Definition
infectious diseases, cancer, endocrine disorders (adenomas, autonomous end-organ function, hormone resistance)
Term
pseudohypoparathyroidism
Definition
Gs alpha defect: mutation = truncated protein. results in short stature, obesity, no knuckles, migratory subcutaneous ossification, resistance to PTH, TSH, LH (all cAMP-mediated hormones) (elevated PTH), hypocalcemia (because PTH regulates serum calcium)
Term
McCune Albright Syndrome
Definition
autonomous endocrine gland activity due to a mutation that activates Gs alpha. = pseudohypopara (inactivating at 37C) + testitoxicosis. mutation is activating at 33C = hypergonadism (precocious puberty). presents with pituitary adenomas, sometimes essential hypertension and sometimes night blindness
Term
"high affinity"
Definition
like longterm dating. come together easily and stay together long time
Term
"pulsatile activation"
Definition
GTPase activity shuts it off
Term
Albright's hereditary osteodystrophy
Definition
pseudohypoparathyroidism. gene that encodes Gs alpha is tissue-specific such that maternally inherited mutations cause hormone resistance but paternally inherited mutations ONLY cause osteodystrophy.
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