cGMP Flashcards
a passage through a cell membrane that uses energy to
move ions or other molecules AGAINST their
concentration gradient
Ion Transport
Ion transporters use
energy like ATP
types / examples Ion transportation
Plasma membrane Ca2+ ATPase
Sodium-calcium exchanger
Sodium chloride symporter
Glycine transporter
Passage through a cell membrane that lets ions flow
DOWN their concentration gradient if it is open; not if it
is closed
Ion Channels
________ equalizes the concentrations on either side of the cell
membrane
Ion Channels
Ion channels accomplish this equalization via ____________ which is a type of _______transport
Facilitated diffusion
Passive
________ is typically one type of ion and activated by changes in electrical membrane potential
Voltage gated Ion channel
_____ is less selective and multiple ions
activated by extracellular ligand binding
Ligand gated ion channels
What are the three classifications for mechanosensitive ion channels
cation
anion
non-selective
_________ activated by mechanical deformation in the membrane
stretch-gated / mechanosensitive
______ ion channel is G-protein regulated
signal-gated
ion channels can be ______________ for fast acting mediation of ion flow across membrane
Ligand gated receptors
Ion channels can be ______________ regulated to mediate slow acting ion channel opening for longer period of time
G-Protein regulated
How are ion channels regulated by GPCR (3)
G protein alpha or beta-gamma subunit
cAMP, cGMP or DAG
PKA or PKC phosphorylation
how do cAMP, cGMP and DAG regulate ion channels?
by directly binding to the channels
what are targets of G proteins so far? 3
AC
PLC
ion channels
What is Rhodopsin
GPCR for retinal rods
in the intracellular membrane.
why is rhodopsin a major GPCR prototype?
Retinal rod outer segment membranes are nearly pure
rhodopsin
therefore rhodopsin was easily identified, purified, studied
what is the ligand for Rhodopsin?
how is it bound?
11-cis-retinal
covalently bound
What is the signal and the detector?
signal : light photon
detector: 11-cis-retinal
what happens when photon hits the 11-cis-retinal,
it causes a conformational change in the retinal, which then changes structure of receptor (C3 loop) and that activates the G-protein transducin
explain the transition from 11-cis-retinaldehyde to all-trans-retinaldehyde ?
which one happens fast?
11-cis-retinaldehyde While bound to receptor; changes receptor conformation when light is detected
Once isomerized, it is clipped off, dissociates
from receptor;
enzymatic re-isomerization,
then covalently reattaches to Rhodopsin- happens fast
What is Transducin?
Transducin is a G protein (alpha, beta and gamma)
abbreviated GT and is a Gi family member
explain what Visual System – Rhodopsin & G protein messenger?
1. Rhodopsin is activated by light. Conformational change leads to activation of G-protein transducin (GT). (release GDP, bind GTP) 2. The GTα•GTP activates cGMP-PDE 3. The cGMP-PDE breaks down cGMP to GMP 4. When cGMP is broken down, it comes off the ion channel which leads to closing of the channel 5. Ions stop flowing, depolarizes membrane, sends electrical signal down optic nerve to the brain
explain Rhodopsin pathway in light vs dark
When it is dark, we make cGMP continuously to keep ion channel open (Burning ATP to pump ions back out) Light turns the cGMP off, closes the ion channel
GT is substrate for what?
a substrate for both cholera and pertussis toxin
In Rhodopsin pathway
________ is secondary messenger
________ is the effector
_________ regulated step
Second messenger = cGMP
Effector for G protein = cGMP phosphodiesterase that
cGMP degradation is the regulated step;
what is the target for cGMP?
membrane ion channel
how is cGMP phosphodiesterase activated?
by alpha-GTP of GT (Gi family)
cGMP is synthesized by
guanylyl cyclase
The ion channels that are the target
of cGMP are________
cation channels for
movement of Calcium and Sodium
__________ the ion channel
cGMP
__________ is degraded by PDE (that is activated by Gt
cGMP
Synthesized by how many guanylyl cylases?
two
particulate membrane GC
soluble (cytosolic) GC
Activates _________ kinase?
PKG
what is the similarity between AMP and cGMP and their Cyclases
They all share that
“anti-parallel dimer” at the catalytic domain
Membrane Guanylyl Cyclase is ____________
enzyme-linked receptor
▪ Receptor and cyclase combined in a single molecule
where dose the hormone and enzyme activity found on enzyme-linked receptor
hormone binding site on
outside, enzyme activity on inside
which part of GC is antiparallel “dimer
cytosolic and that’s where catalytic domain is too
what is Atrial natriuretic factor (ANF, ANP)?
is a peptide hormone
released from the heart
ANP activates what form of guanylyl cyclase
membrane form
high cGMP in kidney ___________ and in blood vessel ________________
Kidney: decreases sodium retention
blood vessel: low blood pressure and volume
_____________ activates Soluble (cytoplasmic) Guanylyl Cyclase
Nitric oxide (NO)
How does NO activates soluble GC and where does it form and where does it act
Changes conformation of the Heme, and then the dimeric
GC
forms in blood vessel endothelial cells in response to stretch and acts in adjacent smooth muscles cells
the activity of the catalytic domain of soluble GC is is regulated by ______
NO
_______ makes NO
NOS- nitric oxide synthase
receptor for NO is _________
soluble GC
NO is _________ signaling whereas ANP is ________ signaling
NO- paracrine
ANP- endocrine
Similarities between AC, mGC and sGC is
- dimers in catalytic domains
- catalytic domains are highly homologous
Differences between AC, mGC and sGC is
- Membrane association
- The regulators
- The sites at which the regulators bind
what is PKG (cyclic GMP-dependent protein kinase):
- cGMP target
- ser-thr kinase
- regulatory/ receptor and
catalytic “domains” on a single peptide chain
cGMP targets
- PKG
- Ion channels
- cAMP phosphodiesterase’s and cAMP
Phosphodiesterase (PDE) breaks __________
a phosphodiester bond
how many PDE families and how do they vary
12
- vary by tissue distribution, substrate
specificity, pharmacological properties,
how do we regulate cGMP? (3)
1. by controlling cGMP breakdown by phosphodiesterases 2. a "soluble" or "cytosolic" guanylyl cyclase 3. a "particulate" or "membrane" guanylyl cyclase
