Biochemistry of Visual Systems Dr. Kinde Flashcards
This cell has rhodopsin and high sensitivity with a low spatial resolution. It can respond to one photon. What is it?
Rods
This cell has three opsins and low sensitivity with high spatial resolution. It will respond to 100 photons. What is it?
Cones
What are the similarities between rods and cones?j
Both have an inner segment, outer segment and a synaptic terminal
Describe why rods have high sensitivity.
- Many rods can converge onto one bipolar cell which will contact one ganglion cell
- High convergence for high sensitivity but low resolution
Descsribe why cones have high resolution
- One cone converges on only one bipolar cell which connects to one ganglion cell
- allows for high resolution but low sensitivity
What is found in the GPCR system of the disc membranes of the outer segments?
- Opsins
- Tranducin (the G protein)
- cGMP phosphodiesterase (effector protein- produces GMP)
What channel is found on the outer membrane of the outer segment of rods and cones and how does it work? (in light and dark)
- cGMP gated sodium channels
- In the dark the cGMP gated sodium channel is open allowing Na to flow in
- In light, when activated, it closes
Beta Arrestin?
- Desensitization protein it allows for signal termination by blocking interaction of rhodopsin with transducin
Rhodopsin kinase?
Desensitization protein that phosphorylates rhodopsin which is the first step in signal termination
In the dark what happens to photoreceptors?
They are inactive!
- cGMP gated Na channels are open and the cell is depolarized
- depolarization allows for release of glutamate
- glu is inhibitory when released to bipolar cells
In the light what happens to photoreceptors?
They are active!
- The light bleaches the rhodopsin molecules
- Na channels are closed and the cell hyperpolarizes due to rapid hydrolysis of cGMP
- Glutamate is not released in a high concentration
Describe the structure of Rhodopsin and significance of a shiff base
- Homologous to B-adrenergic rececptor
- Lysine296 covalently bound to 11-retinal
- Aldehyde of retinal forms a shiff base with amine of lysine
- the protonated schiff base allows for the base to absorb light over 440nm
- free retinal only absorbs 370nm
- unprotonated schiff base only 380 nm
What happens to 11-cis-retinal when it reacts with photons?
Photon induced isomerization occurs
- 11-cis-retinal isomerizes to 11-trans-retinal
- Not ligand binding but energy induced
What chromosomes can you find the opsin proteins for Rods, blue, red, and green?
- Rods: chromosome 3
- Blue 7
- Red and Green are X chromosome
Describe the signal transduction process in the outer membrane of a disc in a rod in presence of light.
- Photons interact with retinal in the photorreceptor and isomerizes to 11 trans retinal activating rhodopsin
- *R makes repeated contacts with transducin molecules activating *G by releaseing GDP for GTP causing the dissosciation of the beta and gamma subunits from the alpha
- *G binds inhibitory gamma subunits of PDE activating its alpha and beta subunits
- Activated PDE hydrolyzes cGMP causing sodium channels to close and hyperpolarization of the cell occurs
- GC synthesizes cGMP this results in decreased levels of cytosolic cGMP causing the cGMP gated channels to close not allowing na and ca in
- as ca levels drop the release of NT glutamate also decreases
How does signal termination occur?
- Rhodopsin kinase phosphorylates the C terminus of metarhodopsin at threonine and serine which allows for binding of arrestin
- Arrestin prevents interaction with transducin
- Rapid hydrolysis of GTP to GDP causes dissociation of alpha subunit from PDE and reassociation with the beta and gamma subunits
- Elevated cGMP levels re open cGMP gated sodium channels and guanylate cyclase synthesises cGMP from GTP
How does low light affect cGMP Na and Ca?
Light causes low cGMP which causes closure of the Na Ca channels reduing intracellular sodium and calcium. Low calcium levels induce recovery
what is the role of Calcium?
- Photon induction decreases cGMP concentrationi
- Resulting in cGMP gated Na channel closure and hyperpolarization due to efflux of K ions
- This decreases calcium concentration (Ca enters Na channel also)
- Guanylate cyclase activity is increased eventually
- This allows for recycling of GMP to make cGMP
By controlling rate of cGMP synthesis Ca levels govern rate by which system is restoree
Where is Retinal produced?
In the retina from vitamin A from the dietary pro-vitamin A carotenoids
What are the 3 vitamin A structures?
- Retinal (aldehyde)
- Retinol (alcohol)
- Retinoic acid (carboxylic acid)
- retinol and retinoic acid are important to maintain epithelial cells and maintaning cornea and conjunctivia
- slupports t cell function as well as male and female reproduction and fetal development
What is the most important nutritional disorder with respect to the cornea?
Vitamin A deficiency. It is typically seen in developing nations and it can increase the likelihood of dying from infections
What is Xeropthalmia?
- Abnormal dryness of conjunctivaa and cornea usually associated with vitamin A deficiency
- This is the second most prevalent nutritional disorder after protein calorie malnutrition
Bitot spots?
Build up of keratin superficially in ocnjunctiva usually foamy
What is accutane?
- Metabolic derivative of retinal used to treat acne
- Caused birth defects on children whose mothers used it while pregnant
How is 11-cis-retinal regenerated? (generally)
- Conversion to all-trans-retinal in the photoreceptors gets transfered to Retinal pigmented epithelial system where it gets isomerized back to 11-cis-retinal.
- Then 11-cis-retinal gets shuffeled back to the photoreceptors
What happens in the rod cell in the retinoid cycle? (This is the first steps in the retinol cycle)
- light induces change from 11-cis-retinal to all trans retinal
- release of all trans retinal from the opsin allows for transport to the cytoplams by the ABC Transporter
- Reduction of the all trans retinal to all trans retinol
- Enzyme is aRDH
- all-trans-retinol is transported out of photoreceptor cell to RPE by binding the iRBP
What happens in the retinoid cycle within the RPE? (Second portion of retinoid cycle)
- all trans retinol is bound to cellular retinoid binidng protein and it gets esterified to all trans retinyl ester by LRAT
- conversion to 11 cis retinol by RPE65 then gets bound to CRALBP
- xidation from 11-cis retiniol to 11-cis retinal by 11-cis-RDH
- iRBP tranports the 11-cis retinal back to the photoreceptors
What occurs if there is a dysfunction in LRAT and RPE65
Retinitis pigmentosa
Recessively inherited
ABC transporter dysfunction
causes build up of trans-retinal within the membrane compromising the health of photoreceptor cells
Retinitis pigmentosa?
- Oxidative and inflammatory changes in RPE due to combo of environment and genetic predisposition.
- Compromises the retinoid cycle!
- Accumulation of retinoid metabolites induces photoreceptor degeneration over time
- Decreased night vision and peripheral vision
- Progressive loss of rods and eventual loss of cone cells
- LRAT RPE65 dysfxn, bony spicules form in the RPE
Macular Degeneration symptoms, risk factors, causes?
- Results in loss of central field vision
- Risk factors:
- Hx smoking
- Obesity
- Causasian
- >70 yo
- low intake antioxidants zince omega3 FA, high fat
- ABC transporters work to transport all trans retinal from the photoreceptors, mutations in ABCA4 causes macular degeneration
LRAT function?
Links all trans retinol to phosphatidyl choline in the membrane to generate all trans retinyl esters within the RPE
