imissyou419's version from 2016-12-18 01:48


Question Answer
cGMP made and degraded bymade by guanylyl cyclase using GTP (Guanylate cyclase takes off first 2 phosphate groups and cyclize remaining phosphate group), degraded by cGMP-phosphodisterase into 5' GMP (no biological effect)
Does GTP have biological effects in terms of signalling?No, but has biological effect at level of G-proteins
Does cGMP have any biological effects in term of signalling?Yes, signalling molecule
Are guanylate cyclase cytosolic and membrane-bound forms related?No, they are not part of the same family, different gene products, do not translocate (unlike PKC)
Characteristics of cytosolic form of guanylate cyclaseCyclase catalytic domain (GTP -> cGMP), Heme-containing domain (metal bind NO and it increases the activity), guanylyl cyclase inhibited by Ca2+ through recoverin
Characteristics of plasmic form of guanylate cyclaseCyclase catalytic domain (GTP -> cGMP), single-pass transmembrane domain, peptide ligand domain extracellularly (viewed as receptor for peptide hormones - mediate effect)
Vascular endothelium lining function in vasoconstriction or vasodilationVascular endothelium lining have receptors that detect hormones in the blood and transmit signal to smooth muscles to vasoconstrict/vasodilate (hormones act on endothelial cells and by releasing secondary transmitter that transiently increasing cGMP levels in smooth muscle cells -> vasodilation)
What happened when you remove endothelium lining from smooth muscle?Add hormones, no increase in cGMP (therefore endothelium plays important role in making of cGMP as receptor, endothelium makes something that can diffuse out of endothelial cell into smooth muscles to increase cGMP in smooth muscles)
What happened when you homogeneous endothelial lining and smooth muscle? No cGMP, must have intact endothelium adjacent to smooth muscle cells
How does hormone mediate vasodilation of smooth muscles?Hormone/NT binds to cell surface receptor on endothelial cells, increases Ca2+ levels in endothelial cells which turns on NO synthase (arginine -> citulline, NO) [CA2+ DEPENDENT] NO diffuse into smooth muscles and increase cGMP (vasodilation); THERE IS NO INCREASE IN CA2+ IN SMOOTH MUSCLE CELLS [CA2+ INDEPENDENT](Ca2+ inhibit guanylyl cyclase through recoverin)
Hormones that increase cytosolic Ca2+ levels in endothelial cells trigger production ofEDRF (endothelium-derived relaxation factor, endogenous vasodilator, intercellular messenger, membrane-permeable so can diffuse into smooth muscle cells, EDRF (NO) stimulate cGMP synthesis by binding to heme group (iron) and activating cytosolic guanylate cyclase in smooth muscle cells)
NO synthase generate NO gas by converting amino aidarginine to citrulline, turned on increased Ca2+ in endothelial cells
Why do you not want NO synthase and cGMP in the same cell?NO synthase is activated by high Ca2+ levels, guanylyl cyclase is inhibited by high Ca2+ levels through recoverin (if both in smooth muscle cell, high Ca2+ turn on NO synthase, guanylyl cyclase is inhibited by Ca2+ so no cGMP made and no vasodilation)
How long is the half-like of NO and what is it converted to?5-10 seconds, which limits its action to adjacent cells, NO rapidly converted to nitrites and nitrates by oxygen and water
What does nitroglycerine do?NO gas medicine leads to rapid vasodilation of the heart
What are the Ca2+ and calmodulin dependent NO synthasesnNOS (neuronal), eNOS (epithelial) - Ca2+ activate them, has Ca2+ calmodulin binding sites
What are the Ca2+ and calmodulin independent NO synthasesiNOS (inducible) in macrophages- as soon as enzymes is produced and in right compartment, it is active
What is the enzyme catalytic activity (making NO) of Ca2+ dependent NOS and Ca2+ independent NOSCa2+ dependent is activated at increased cytosolic Ca2+ levels "induced", Ca2+ independent NOS is CONSTITUTIVELY ACTIVE (when it is made, make a lot of NO which is toxic to bacteria but has short half-life)
What is the expression (protein expression) of Ca2+ dependent NOS and Ca2+ independent NOS
Ca2+ dependent NOS is CONSTITUTIVE - cells normally have proteins there all the time but not active unless increased Ca2+ levels and do not have to make protein in response, Ca2+ independent is INDUCIBLE - macrophages normally do not have iNO synthase and is made on cue
Membrane-bound guanylate cyclaseseveral peptide hormones cause cGMP synthesis - atrial natriuretic peptide (ANP or ANF), (made in the heart and has natriuretic, diuretic, and smooth muscle relaxant actions), brain natriuretic peptide and ACTH; peptide receptor that transmit information by turning on guanylate cyclase
T/F - Ligand binding receptor is coupled with guanylate cyclase catalytic domain by G-proteinF, ligand binding receptor is NOT coupled to cyclase by G-protein, they are on the same protein (unlike receptor-mediated activation of adenylyl cyclase)


Question Answer
outer segmentphotoreceptive apparatus
inner segmentmany mitochondria
synaptic regionmakes synaptic contact with nerve cells of the retina
What type of neurotransmitter is released from rod cells to nerve cells of the retina?inhibitory NT released in a Ca2+ dependent matter through AP (the amount of inhibitory NT released will increase or decrease AP firing rate of target cell)
In the darkrhodopsin is inactive, cGMP-phosphodiesterase falls off, high cGMP in rod cells, high probability of cGMP bind to cation (Ca2+ and Na+) channels and keep them open -> rod cell is depolarized, cytosolic Ca2+ levels high with high rate of inhibitory NT release (cGMP is high NOT because guanylate cyclase is actively making it but because phosphodiesterase is low - High Ca2+ = high probability of Ca2+ to bind to recoverin, recoverin assumes conformation with high binding affinity for cytosolic guanylate cyclase and form heterodimer hiding cyclase catalytic domain)
In the lightPhotons of light hits retinal chromophore, retinal undergoes conformational change, rhodopsin receptor undergoes conformational change, engage G-protein transducin (exchange GDP for GTP), activate effector cGMP-phosphodiesterase which decreases [cGMP] so cGMP dissociate from cation channels and the probability of rebinding is less so they close (+ Ca2+ pumped out of cell using ATP), as Ca2+ falls, Ca2+ dissociate from recoverin, guanylate cyclase dissociate from heterodimer conformation and catalytic domain expressed, increasing guanylate cyclase activity to make cGMP -> rod cell is repolarized/hyperpolarized, decreased Ca2+ influx and decreased release of inhibitory NT, neuron can send AP to brain
rate of NT release from rod cells isGRADED TO LIGHT INTENSITY (little bit of light -> a lot of inhibitory NT release, even more light -> even less release of inhibitory NT, even more light -> even less release of inhibitory NT); amount of NT release determine firing frequency of neuron
RhodopsinGPCR, has chromophore (vitamin A analog called retinal), retinal undergoes conformational change when photon hits it -> changes conformation of receptor -> receptor recognize G-proteins -> cascade of events -> change cGMP levels [this is the only light-dependent step in vision]
What happens when you have a vitamin A deficiency?cannot make retinal, rhodopsin will not work because there is no good retinal associated with the receptors
What happens when you use inside-out patch of membrane from the outer segment of rod cell and exposed it to cGMP and ran it under V-clamp conditionswhat faced inside now faced outside (test solution with cGMP), increase in current flow - "dark current", this current stayed up as long as cGMP was present (to keep cation channels open)

If you put cAMP or 5' GMP, do not have dark current suggesting it is selective for cGMP
Amplificationabsorption of single photon of light by single molecule of rhodopsin leads to amplification of signal(huge amplification @ phosphodiesterase chopping up lots of cGMP molecules leading to closure of lots of cation channels) which only leads to 1 mV change
How does [Ca2+] regulate cytosolic guanylate cyclase activity?indirectly through recoverin; When Ca2+ levels are high, Ca2+ binds to recoverin and recoverin assumes conformation with high binding affinity for cytosolic guanylate cyclase and form heterodimer which hides cyclase catalytic domain

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