Biochemistry of Visual System (Kinde) Flashcards
Rods Characteristic
- Light detection
- 100 million present
- 1 opsin - Rhodopsin
- Respond to a single photon
- Many rods converge into a single bipolar cell
- high sensitivity but low resolution (Example: Many witnesses simulatneously describing a suspect to a cop)
Cones Characteristics
- Color detection
- 7 million of them
- Three opsins (Red, green & blue)
- Need ~100 photons to respond
- low sensitivity but high resolution
- 1 cone directly contacts 1 bipolar cell (Example: 1 witness giving a detailed description of a suspect to a cop)
Explain what happens in the dark/default state in photoreceptors
Default = Depolarized = Cell is always active and releases Glutamate (inhibitory NTs)
Explain what happens to photoreceptos in the presence of light
Light = cell hyperpolarized = decrease in presence of Glutamate
What is Rhodopsin
A 7 transmembrane protein receptor found in Rods that detects light
What are the structural features of Rhodopsin
In the center of rhodopsin, Lysin-296 is covalently bound to 11-Retinal forming a schiff base called 11-cis-Retinal. The shiff base is protonated to absorb more light.
How much light does the protonated schiff base absorb
> 440 nm
What happens to Rhodopsin in the presence of light
11-cis-Retinal isomerizes to all-trans-retinal causing a conformational change in Rhodospin
What is Retinal derived from
Vitamin A
What are the opsin’s found in Cones?
Blue, red & green opsin
What is the absorption maxima & chromosome # of the Blue opsin protein
420 nm
Chromosome 7
What is the absorption maxima & chromosome # of the Red opsin protein
560 nm
X chromosome
What is absorption maxima & chromosome # of the Green opsin protein
530 nm
X chromosome
Can AMAB individuals affected with red/green color blindess pass the trait of to their offsprings?
Why?
No, but they will have carrier daughters. If wife passes on affected gene as well, the daughter would be positive for the trait.
Because Red/green colorblindness is X-linked Recessive.
Would need 2 copies of affected X chromosomes for females to be affected but only 1 for males to be affected.
Can unaffected AFAB carriers pass R/G color blindess trait to their offsprings?
If so, which gender and why?
Yes, the trait can be passed on to their AMAB offspring
R/G color blindness is X linked recessive. A female carrier would only need to pass the 1 affected gene to her son to be affected
Explain the signal transduction pathway for photoreceptors
- Presence of light causes isomerization of 11-cis-retinal –> all-trans-retinal leading to a conformational chage in Rhodopsin, activating it.
- Rhodopsin activates GPCR Transducin, allowing it to exchange it’s GDP for GTP. GTP bound transducin’s α subunit dissociates from it β and γ subunits.
- Transducin-α binds to phosphodiesterase (PDE) inhibitory γ subunit, actiavting PDE.
- Activated PDE hydrolyzes cGMP, lowering the conc. of cGMP and therefore closing the Na+/Ca2+ channels, hyperpolarizing the cell which allows signal propagation to occur.
- Decreased intracellular Ca2+ leads to a decrease in the amount of Glutamate being realeased by the cell (vesicle fusion decreases).
Function of Guanulyl Cyclase (GC) and how is it regulated
- GC is the enzyme that produces cGMP from GTP.
- It is controlled by Calcium levels. Once the intracellular Ca2+ lvls diminish to a specific threshold due to the Na+/Ca2+ channels closing, that triggers GC to produce more cGMP which is turn opens up the Na+/Ca2+ channels .
How are the photoreceptor signals terminated
- Rhodopsin kinase phosphorylates the C-terminus of Rhodopsin at the Thr & Ser residues, allowing Arrestin to bind which prevents interactions with transducin.
- Rapid hydrolysis of GTP to GDP causes dissociation of Transducin-α subunit from PDE & reassociation with the β and γ subunits.
- Guanylate cylase synthesizies cGMP, elevating cGMP levels which re-open cGMP-gated Na+ channels depolarizing the cell.
What is the role of Ca2+ in the signal transduction process in rod and cone cells
INDUCE RECOVERY
Ca2+ govern the rate by which the system is restored by controlling the rate of cGMP synthesis by Guanylyl Cyclase (GC)
What are the 3 Vitamin A structures
Retinol (Hydroxyl FG)
Retinoic Acid (Carboxyl FG)
Retinal (Aldehyde FG)
Vitamin A deficiency
The most important nutritional disorder with respect to the cornea & increases the likelihood of dying from infections
What are some disorders associated with Vitamin A
Night blindness
Visual impairment
Xerophthalmia (dry eye syndrome)
Bitot’s spots (due to keratin debris in conjunctiva)
growth impediment
failure of wounds to heal well
dry skin
alopecia
lung conditions: bronchitis & pnemonia
What are the effects of kids exposed to Isotretinoin/Accutane (Vitamin A derivative) in the womb
Cleft palates & heart abnormalities
What is the first genetically designed biofortified food that was created to treat Vitamin A deficiency
Golden Rice
How is 11-cis-retinal regenerated
Through a series of enzymatic steps in two cellular systems:
- Photoreceptors (rods/cones)
- Retinal pigmented epithelium (RPE)
What is the function of ABC transporters in the retinoid cycle
ABC transporters move all-trans-retinal from the photoreceptors into the cytoplasm
Clearance of 11-trans-retinal from photoreceptors
How is all-trans-retinal converted to all-trans-retinol
all-trans retinol dehydrogenase (aRDH)
What transporter facicilates movement between the photoreceptor and retinal pigmented epithelium (RPE) in the Retinoid cycle
inter-photoreceptor retinoid binding protein (iRBP)
What is the function of LRAT
Converts all-trans-retinol –> all-trans-retinyl esters
What is the function of RPE65
Converts all-trans-retinyl ester –> 11-cis-retinol bound to CRALBP
CRALBP = cellular retinaldehyde binding protein
What causes Retinitis Pigmentosa
LRAT & RPE65 dysfunction causing an oxidative and inflammatory change in retinal pigmented epithelium (RPE) due to a combination of environmental factors and genetic predisposition which can lead to an accumulation of retinoid metabolities and induce photoreceptor degeneration
What are the effects of Retinitis Pigmentosa
Decreased night vision & peripheral vision
Mutations in what protein are known to cause macular degeneration and related disorders associated with severe central vision loss
ABC transporters
Degeneration of the macula in the retina results in what
Loss of central field vision
What are some risk factors for Macular degeneration
Advance age, especially over 70
History of smoking with past 20 years
Dietary factors
Obesity
Caucasian
Explain the 11-cis-retinal regeneration step that occurs in the photoreceptors
- Release of all-trans-retinal from opsin
- Transport of all-trans-retinal to the cytoplasm by ABC transporter
- Enzymatic reduction of all-trans-retinal to all-trans-retinol (Vitamin A) by all-trans-retinol dehydrogenase (at-RDH)
- Transport of all-trans-retinol to RPE by interphotoreceptor retinoid binding protein (iRBP)
Explain the 11-cis-retinal regeneration step that occurs in the Retinal pigmented epithelium (RPE)
- all-trans-retinol bound to retinoid binding protein (CRBP) undergoes esterification to all-trans-retinyl by lecithin retinol acyl transferase (LRAT)
- all-trans-retinyl is converted to 11-cis-retinol by RPE65
- 11-cis-retinol is oxidized to 11-cis-retinal by 11-cis-RDH
- iRBP transports 11-cis-retinal to the photoreceptors then a colavent schiff base attachment forms a functional rhodospin
