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Retinal Photochemistry
Biochem
94
Biochemistry
Graduate
03/13/2012

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Cards

Term
Which protein acts as the receptor of photons?
Definition
Rhodopsin
Term
When it receives a photon, what does Rhodopsin activate?
Definition
It activates the G-protein Transducin
Term

Name the 6 main classes

 of cells found in the retina

Definition

Rods

Cones

Horizontal

Bipolar

Amacrine

Ganglion cells

Term
What type of receptor is Rhodopsin?
Definition
A G-protein coupled receptor
Term
What are the 2 major groups of Opsins?
Definition

R-opsins, rhabdomeric

C-opsins, ciliary

Term
What color of light does rhodopsin absorb the most?
Definition
Green (wavelengths ~500nm)
Term
Which color of light are r-opsins insensitive to?
Definition
Red
Term
In the amino acid sequence of rhodopsin, what amino acid does 11-cis-retinal bind to?
Definition
Binds to Lysine 296
Term
Which rhodopsins are scotopsins and which are photopsins?
Definition

Rod rhodopsins are scotopsins

Cone rhodopsins are photopsins

Term
Which protein is involved in Retinitis Pigmentosa?
Definition
A mutation in Rhodopsin causes Retinitis Pigmentosa
Term
Describe the 'movement' of the subunits when transducin is activated.
Definition
The beta and gamma subunits fall off, leaving the remaining alpha subunit as the activated part. 
Term
What does the activated alpha subunit of transducin do?
Definition
It binds to and activates Phosphodiesterase (PDE)
Term
What does Phosphodiesterase do in the visual cycle?
Definition
Phosphodiesterase hydrolyzes cGMP to GMP, which closes the cGMP gated channels
Term
Explain how the closure of cGMP gated channels affects the cells voltage
Definition
The closure of these channels disrupts the dark current and results in hyperpolarization of the cell. 
Term

Compe phosphorylated Rhodopsin (Rh*-P) to 

phosphorylated rhodopsin bound to arrestin (Rh*-P-Arr)

Definition

Rh*-P retains partial activity

Rh*-P-Arr is fully inactive

Term
What does 11-cis-Retinal isomerize to when a photon is absorbed?
Definition
All-trans-Retinal
Term
What does Rhodopsin get converted to before it activates Transducin?
Definition
Metarhodopsin II
Term
How many subunits does phosphodiesterase have and what are they?
Definition

4

Alpha

Beta and two gamma

Term
Explain how GDP and GTP are involved in the activation of transducin
Definition
When metarhodopsin II activates Transducin, not only do the beta and gamma subunits fall off but GDP is exchanged for GTP, producing G-alpha-GTP
Term
Explain the movement of subunits of transducin and phosphodiesterase in the process of activating phosphodiesterase
Definition

When activated the beta and gamma subunits of Transducin-GDP fall off, leaving alpha-GTP. 

2 alpha-GTP bind to the 2 gamma subunits of phosphodiesterase, which are inhibitory. 

This causes the release of the alpha and beta subunits of phosphodiesterase, thus removing their inhibition. 

They then catalyze the hydrolysis of cGMP. 

Term
Describe the 2 levels of deactivation of rhodopsin
Definition

1. Receptor kinase phosphorylates Rhodopsin

2. Arrestin interacts with the phosphate group and interrupts interaction between Rhodopsin and Transducin. 

Term
What functional groups bind to the phosphate group in deactivation of rhodopsin?
Definition
Serine and Threonine allow the phosphate to bind to rhodopsin
Term
How does Calcium affect the receptor kinase (RK)
Definition
High levels of calcium inhibit the receptor kinase, stopping it from phosphorylating and subsequently deactivating rhodopsin. 
Term
How do high levels of calcium affect rhodopsin activity?
Definition
High calcium levels prevent deactivation of rhodopsin.
Term
How do low levels of calcium affect rhodopsin
Definition
Low levels of Calcium allow the receptor kinase to work and desensitize rhodopsin
Term
How is transducin deactivated?
Definition

The alpha subunit of Transducin has its own GTPase. 

Thus it can convert the G-alpha-GTP to G-alpha-GDP (dephosphorylated form)

Once this occurs, the beta and gamma subunits return, forming inactive transducin.

Term
What is the rate limiting step in the deactivation of Transducin?
Definition
The action of the GTPase which removes one phosphate from the alpha subunit, to form alpha-GDP. 
Term
How is phosphodiesterase deactivated?
Definition
The 2 gamma subunits return to the alpha and beta subunits
Term
Are the cGMP-gated cation channels specific or non-specific.
Definition
Non-specific, they will let any cation through
Term
cGMP gated channels are  (blank) in the dark and (blank) in the light
Definition

Blank 1- Open

Blank 2- Closed

Term

Ca2+ carries how much of the dark current?

What carries the rest of it?

Definition
Ca2+ carries 15% of the dark current and Na+ carries the rest of it.
Term
What molecule modulates the activity of the receptor kinase in response to Calcium?
Definition
Recoverin
Term
What molecule makes cGMP from GTP?
Definition
Guanylate Cyclase
Term
How does Calcium affect the activity of Guanylate Cyclase?
Definition

High calcium inhibits Guanylate Cyclase 

Low calcium allows GC to be active and produce cGMP

Term
How does calcium affect the CNG channels?
Definition
A decrease in calcium leads to an increase in affinity of CNG channels for cGMP
Term
Describe 3 roles of Calcium in the visual pathway
Definition

1. A decrease in calcium activates the receptor kinase

2. Decrease activates GC

3. Decrease increases the affinity of CNG channels for cGMP

Term
How does calcium affect cGMP levels?
Definition

High calcium inhibtis GC, thus decreasing levels of cGMP

Low levels activate GC, increasing levels of cGMP

Term
Which is faster, rods or cones?
Definition
Cones have faster activation and recovery
Term
Name 2 membrane proteins found in the discs (outer segment) that contribute to structure
Definition
ROM-1 and Peripherin
Term

11-cis-RAL gets converted to all-Trans-RAL,

then what happens to all-Trans-RAL?

Definition
It gets Reduced to all-trans-ROL
Term
Where does the reduction of all-trans-RAL to all-trans-ROL occur?
Definition
In the rod/cone  
Term
What happens to all-trans-ROL once it is formed from all-trans RAL?
Definition
It gets transported from the photoreceptor into the Retinal Pigment Epithelium cell
Term
What happens to all-trans-ROL once inside the retinal pigment epithelium?
Definition
Esterification of all-trans-ROL, forming all-trans-R-Ester
Term
What is the next step in the visual cycle after all-trans-R-Ester is formed?
Definition
It is converted into 11-cis-ROL
Term

all-trans-R-Ester --> 11-cis-ROL

What enzyme?

Definition
Isomerohydrolase (RPE65)
Term
What is the next step in the visual cycle once 11-cis-ROL is formed?
Definition
11-cis-ROL is oxidized to 11-cis-RAL
Term
What happens to 11-cis-RAL once it is formed in the RPE cell?
Definition
Gets transported into the photoreceptor
Term
Where does the oxidation of 11-cis-ROl to 11-cis-RAL occur?
Definition
In the RPE
Term
Where does the conversion of All-trans-R-Ester to 11-cis-ROL occur?
Definition
In the RPE cell
Term
Name the 4 forms of Vitamin A discussed
Definition

Retinol

Retinal

Retinoic acid

Retinyl Ester

Term
What functional role does Retinol have?
Definition
Transport
Term
What functional role does Retinal have?
Definition
Visual transduction
Term
What functional role does Retinoic acid have?
Definition
Synthesis
Term
What functional role does retinyl ester have?
Definition
Storage
Term
Of the 4 forms of Vitamin A, which one has a role in storage?
Definition
Retinyl Ester
Term
Which of the 4 forms of Vitamin A plays a role in transport?
Definition
Retinol
Term
Which of the 4 forms of Vitamin A plays a role in Visual 
Transduction? 
Definition
Retinal
Term
Which of the 4 forms of Vitamin A plays a role in Synthesis
Definition
Retinoic Acid
Term
What do RPE cells have the Muller cells do not?
Definition
RPE65
Term
How do cones use Muller cells in the visual cycle?
Definition
Muller cells can be used to recycle all-trans-ROL back into 11-cis-ROL (instead of this being done in the RPE cell)
Term
Which substance in the visual cycle is involved in Retinitis Pigmentosa?
Definition
Rhodopsin
Term
What part of the visual cycle is involved in Stargardt's disease?
Definition
Mutation in the gene for ABCA4
Term
Which part of the visual cycle is involved in Leber's congenital amaurosis?
Definition
RPE65 mutation
Term
Describe what can happen if all-trans-RAL accumulates in the RPE cells rather than being recycled properly.
Definition

all-trans-RAL will react with phosphatidylethanolamine to from A2E

A2E then reacts with light to form free radicals which damage the RPE cells

Term

Rods are for (blank) resolution

Cones are for (blank) resolution

Definition

Rods-temporal resolution

Cones-spatial resolution

Term
All Rod bipolar cells are ON/OFF (pick one)
Definition
They are all ON, they depolarize in the presence of light
Term
Name the 2 types of glutamate receptors
Definition

Metabotropic

Ionotropic

Term
Which are faster, metabotropic or ionotropic receptors?
Definition
Ionotropic receptors are faster
Term
If Metabotropic receptors are G-protein coupled receptors, what are Ionotropic receptors?
Definition
Ligand gated ion channels
Term
What neurotransmitter is associated with A2?
Definition
Glycine
Term
What neurotransmitter is associated with A17
Definition
GABA
Term
What neurotransmitter is associated with A18
Definition
Dopamine
Term
What is the function of A2 cells?
Definition

Transmit signal between

-rod bipolars and ganglion cells (via amacrine)

or

-rod bipolars and cone bipolars

Term
Which types of bipolar cells (ON or OFF) synase in sublamina A
Definition
OFF cells synapse in sublamina A, which is more outer than B, ie. closer to the RPE
Term
Which layer do the ON bipolar cells synapse in
Definition
Sublamina B, which is more inner than A, closer to the ganglion.
Term

An OFF center cell

Light on the surround only

How will the cell respond?

Definition
The cell will fire rapidly
Term

Have an ON center cell

There is light on center and surround

How will cell respond?

Definition
There will be a weak response, low frequency firing
Term
Considering Tonic and Phasic Cells, which are for color and which are for movement?
Definition

Tonic are for color

Phasic are for movement

Term
Considering Phasic and Tonic cells, which is similar to Parvo cells and which is similar to Magno
Definition

Tonic cells are similar to Parvo-they 'see' resolution and detail

Phasic cells are similar to Magno -->motion detection

Term
Define ipRGCs
Definition
intrinsically photosensitive Retinal Ganglion Cells
Term
How are ipRGCs different from other Ganglion cells?
Definition
ipRGCs respond to the photopigment Melanopsin
Term
How do ciliary and rhabdomeric pigments differ in their response to light?
Definition

Ciliary pigments result in hyperpolarization due to the presence of light

Rhabdomeric - depolarization in response to light. 

Term
Name 3 Mechanisms of photoadaptation
Definition

1. Pupil constriction

2. Photochemicals (hyperpolarization decreases glutamate release)

3. Neural processing-modulation by amacrine and horizontal cells etc. 

 

Term
Do we adapt faster to dark environments or bright environments?
Definition
We are faster when adapting to light compared to dark environments. 
Term
Name 3 types of non-neuronal cells found in the retina
Definition

1. Muller cells

2. Astrocytes

3. Microglia

Term
What supplies blood to outer retina?
Definition
Choroid
Term
What supplies blood to the inner retina?
Definition
Central Retinal arteries
Term
How is the majority of glucose consumed in the retina? (Aerobically, anaerobically or PPP)
Definition
60% of glucose is consumed anaerobically
Term
What aspect of glucose metabolism plays an important role in the production of antioxidant molecules?
Definition
The metabolism of glucose via the PPP pathway produces antioxidant molecules.
Term
How is the majority of ATP produced in the retina? (Aerobically or anaerobically)
Definition
Majority of ATP is produced Aerobically
Term
How can glutamate be incorporated in ATP production in the retina
Definition
Glutamate can be converted to alpha-ketoglutarate which can then enter the Kreb's cycle. 
Term
Name 3 substances that the retina can use to produce ATP in addition to glucose
Definition

Glutamate

Malate

Succinate

Term
Name the 2 most abundant retinal lipids
Definition

Phosphatidylcholine

Phosphatidylethanolamine

Term
What is the  major carrier of Vitamin A in the blood?
Definition
Transthyretin
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