Test 3: 46 and 47 Flashcards
Your patient suffers from excessive thirst and is excreting large volumes of dilute urine. Plasma osmolarity is increased, but urine osmolarity is decreased. What is the problem and what is the cause?
Your patient suffers from nephrogenic diabetes Insipidus, an improper response of the kidney to ADH, leading to a decrease in
the ability of the kidney to concentrate the urine by removing free water. This is caused by mutations in the vasopressin V2 receptor
Your patient suffers from retinitis pigmentosa. What is the problem and what is the cause?
Mutation in the rhodopsin gene causing retinal degeneration
___ are the largest family of transmembrane receptors
G protein coupled receptors (GPCRs)
Half of GPCR are devoted to ___
sensory transduction
G protein coupled receptors
GPCRs help with ___
sensory transduction, neural, physiological and cardiovascular functions
GPCR pathway overview
GPCR (7-TMR: 7 alpha helical)
Trimeric G protein
Cyclic nucleotides
membrane channels
membrane signals
gene regulation
the __ subunit of G proteins binds to GTP
alpha
explain how light gets to brain
light interacts with photoreceptors in the back of the eye that are imbedded in a pigment epithelium
those photoreceptors interact with bipolar cells which interact with ganglion cells that form together to form the optic nerve
Two types of photoreceptor cells?
rod and cones
___ are photoreceptor cells that help with night vision.
Rods
___ are photoreceptor cells that help with day vision.
cones
Which photoreceptor cells detect color?
cones
rod cells
about 100 million per retina
Very sensitive to light
Vision in dim light (night vision)
cone cells
about 3 million per retina
Less sensitive to light
Vision in bright light, detect color
there are more rod cells than cone cells in the eye. True or False
True
100 million rods, 3 million cones
the outer segment of a rod cell are filled with
membrane discs
What is the light receptor that sits on the membrane disc of rod cells?
rhodopsin
N terminal faces outward of cell
C terminal faces toward nucleus
what is the name of the protein that sits inside rhodopsin?
11 cis retinal
where does 11 cis retinal come from
carrots
Beta carotone → all trans retinal
what does light do to 11 cis retinal
changes from 11 cis retinal
to
all trans retinal
rhodopsin + light=
unusual properties of 11 cis retinal
stability- when in dark very stable in cis form
sensitivity- if hit by photon of light will quickly flip from cis to trans form
visual pathway in a nut shell
rhodopsin +light→ activated rhodopsin
activated R will activate transducin to bind to GTP instead of GDP
active transducin will activated PDE (phosphodiesterase)
PDE will make cGMP to GMP
decrease in cGMP will cause channels to close which membrane hyperpolarization which will cause signal to travel across neuron to brain saying “we saw the light!”
amplification step of light
1 rhodopsin can activate 500 transducin
activated PDE can cleave cGMP to GMP at 4200 GMP per second = very fast drop of cGMP in the cell
In the dark, sodium flow into the cell through the channels yielding a depolarized rod cell membrane. At the synaptic terminal ___ is released to signal bipolar nerve cells causing a “dark current”.
glutamate
In light, the rod membrane channels close yielding a ___ membrane. This leads to less ___ released at the synaptic terminal and a reduction in signal to the bipolar nerve cells. This indicates light has been detected.
hyperpolarized
glutamate
A decrease in glutamate released at the synaptic terminal indicates ___ has been detected
light
decrease in cGMP = Na+ channels close, no Na into cell= hyperpolarization of membrane =less glutamate released
what cause Na channels to close when light hits rods?
cGMP decreases
light activated Rhodopsin which binds to transducin, this causes transducin to let go of GDP and bind to GTP. alpha subunit of activated transducin then leaves and binds to gamma subunit of PDE. This activates PDE to change cGMP to GMP= decreased cGMP in cell = Na+ channels close, no Na into cell= hyperpolarization of membrane =less glutamate released
when light hits cell, Na and Ca are not brought into cell because channel is closed. This decrease in calcium leads to ___
activation of guanylate cyclase, which leads to synthesis of cGMP, which leads to opening of Ca, Na channels in cell
Low Calcium in cell after light hits: activates guanylate cyclase. ___ increases.
cGMP
GTPase of transducin: Transducin goes from GTP to GDP state, releases ___. So PDE and Transducin are inactivated.
gamma subunit of PDE
Rhodopsin: Phosphorylated by rhodopsin kinase and interacts with ___ to stop signal to transducin.
arrestin
how to stop rhodopsin from interacting with transucin
Phosphorylated by rhodopsin kinase and interacts with arrestin to stop signal to transducin.
Rhodopsin internalized: convert 11-trans to ___ , remove phosphates on rhodopsin, and recycle ___ to cell surface.
11-cis retinal
rhodopsin
___: in light it binds to transducin beta gamma subunits. This keeps transducin alpha active longer: keeps pathway activated
Phosducin
Phosducin: in light it binds to transducin ___ subunits. This keeps transducin __ active longer: keeps pathway activated
beta gamma
alpha
Phosducin: in dark is ___ and no longer binds transducin beta-gamma subunits. Reduces transducin activity and keeps pathway in ___ activity.
phosphorylated
lower
Mutation in the rhodopsin gene causing retinal degeneration called ___
retinitis pigmentosa
treatment for retinal degeneration
Vitamin A
Omega3 fatty acids
Retinal cell transplants
Growth factors
Retinal prosthetic devices that detect light
Gene Therapy
Achromatopsia
treatment:
can only see in dark and black and white, no colors; daylight vision impaired
gene therapy
when light hits rhodopsin what happens first?
11 cis retinal is converted to 11 trans retinal
what is the role of arrestin in the visual pathway
it binds to phosphorylated rhodopsin
In the visual pathway, what is the tole of recoverin
to active guanylate cyclase
where is 11 cis retinal derived from
vit A
what is a major function of the membrane discs in the outer segment of rod cells?
to increase SA to allow more space for rhodopsin
what protein domain usually interacts with membranes
FYVE domain
what is a main function of scaffold proteins
to efficiently link kinases in a signaling pathway
most growth factors exert their function in what stage of the cell cycle?
G1
Why are anti-angiogenic drugs believed to be potentially useful for anti cancer therapy?
They specifically target the growth of normal endothelial cells
which of the following expresses multiple different sensory receptors per cell?
rod
cone
olfactory receptor
gustatory receptor
sensitivity training
gustatory receptor
what is red-green the most common form of color blindness?
the red and green receptor genes lie near each other and often undergo recombination
in the dark, how often does 11 cis retinal spontaneously change to 11 trans retinal?
once every 500 years
three cone receptors
blue 455
green 530
red 625
why is color blindness more common in males?
red and green sit on X chromosome
what are some species differences of color perception?
olfactory epithelium (pseudostratified)
olfactory cells stretch into the basal membrane and at the other end have olfactory vesicles
sustentacular cells- microvilli
olfactory vesicle have ___ to increase surface area
cilia
Insect pheromones can be detected at a few molecules ___
per animal
Some airborne odorants are detected at parts per ___
trillion
how many categories of smells?
13
Genetics suggests hundreds or more receptors.
Fruity, Amines, Herbaceous, Organic Acids, Minty, Sulphydryl Compounds, Floral, Methoxy Pyrazines, Putrid, Alkyl Pyrazines, Aromates, Stereoisomers and Aldehydes
People with ___ cannot detect particular categories of odor molecules.
anosmias
biochemistry of olfaction
- Cell Surface Receptors
- Trimeric G Proteins- Golf for Olfaction
- Cyclic Nucleotides Adenylate Cyclase and cAMP (make more cAMP)
- Membrane Channels open
- Nerve Impulse
- Deactivation of Biochemical Pathway
- Clearing of Odorant Molecule
difference between vision and smell biochemistry
Cell Surface Receptors
- Trimeric G Proteins
Golf for Olfaction
Transducin for Vision
- Cyclic Nucleotides
Adenylate Cyclase and cAMP for Olfaction (make cAMP)
Phosphodiesterase and cGMP for Vision (breakdown cGMP)
- Membrane Channels
Open for Olfaction (depolarization)
Close for Vision (hyperpolarization)
- Nerve Impulse
- Deactivation of Biochemical Pathway
- Clearing of Odorant Molecule
Olfactory Receptors are expressed from only one ___ ,and only one ___ per receptor cell.
allele, (mom or dad not both)
receptor gene
how to deactivate smell
slow suppression: neural
fast suppression: biochemical: phosphorylation of Golf and binding of arrestin to receptor
cytochrome P450 helps clear odorants
___ helps clear odorants from smell receptors
cytochrome P450
why is olfactory system so sensitive
- Air-Water Partition
- High Surface Area due to Olfactory Cilia
- High Density of Receptor Proteins in the Membrane
- Biochemical Amplification
- Neural Processing
5 types of taste
sweet
salty
bitter
sour
umami(mono-sodium glutamate)
Gustatory system has ___ receptors
50-80
how does gustatory system work
- Gusducin(g protein): binds GTP or GDP
- Activates PDE: cleaves cAMP to AMP
- Closes sodium membrane channel
g protein of taste system
gusducin
g protein of sight system
transducin
in vision c___ turns into ___
while in taste c___ turns into ___
in smell ___ turns to ___
cGMP → GMP
cAMP → AMP
AMP → cAMP
in taste ___ receptor can be expressed in each cell, this is different from sight and smell with ___ receptor per each cell
multiple
one
GPCR can effect
Vision
Olfactory
Gustatory
Neurotransmission: Behavior, serotonin, dopamine, GABA, glutamate
Immunity: Chemokine receoptors
Autonomic nervous system: Blood pressure, heart rate, digestion
Homeostasis: Water balance
Growth and Metastasis
