Biochemistry of the Visual System Flashcards
Photoreceptors Rod and Cone
Rods: Rhodopsin and detect light (no color)
High Sensitivity and low spatial resolution
MOST
Can respond to a single photon (retinal ganglion cell) ->Many Biopolar cells ->Many RODS
Cones: 3 Opsins (Red, Green, Blue)
Low sensitivity and high spatial resolution
One Retinal Ganglion Cell -> one bipolar cell-> one CONE
The outer segment membrane of the photoreceptors have Disc Membranes stacked inside and in these are:
GPCR System:
- Opsin [rhodompsin]
- Transducin (The G protein)
- cGMP Phosphodiesterase (effector protein)
The outer segment membrane has:
cGMP-gated Na+ channels
OPEN: dark , depolarized glutamate photoreceptor cell
CLOSE: light, hyperpolarized glutamate photoreceptor cell
Desensitization Proteins:
- B-Arrestin
- Rhodopsin
The 7TM Receptors
1/3 of all drug targets
Rhodompsin and opsin are examples
7TM protein
Opsin (Rhodopsin) Receptor
B-Adrenergic Receptors homologous
Lys296 (in the middle)+Retinal 11(VitA)= Schaffer base
LIGHT: isomerization causes rotation = 11-cis-retinal -> 11-trans-retinal
Light Absorption for Rhodopsin and the Cone receptors
Rod: 500nm. (3chr)
Blue: 420nm. (7chr)
Green: 530nm. (Xchr)
Red: 560nm. (XChr)
Signal Transduction: what happens in the membrane of the inner disc and the outer segment membrane
- Photon comes and causes isomerization from cis to trans, activating rhodompsin (meta-rhodompsin or Rh*)
- Meta- rhodopsin contacts the GDP-transducin =GTP-Transducin
- Causing cleavage of the a subunit of the transducin, which goes and contacts the cGMP Phosphodiesterase (PDE6) activating it
- cGMP->GMP hydrolysis
- Decreases cGMP (ligand to the Na+ channels on the outer segment membrane)
- Na+/Ca+ channel deactivated and Na+ channel closes
- Hyperpolarization
- Stop glutamate inhibitory NT release, cause in signal cascade to happen
Ca+ that comes in though the Na+ channel
Stops GC; so GTP does not become cGMP, and keeps channel closed
So when Ca+ is low due to closed channel, the GC is activated increasing cGMP and that opens the Na+/Ca+ channel
CA+2 controls the RATE at which the photoreceptors are desensitized and restored, by controlling the rate of cGMP synthesis
Amplification
One photon goes to one rhodopsin receptor
- > many G-protein transducins activated
- > many PDE6 activated
- > many GMP Made and many cation channels closed
- > membrane potential changes to 1mV and signal goes to brain
Signal Termination (Desensitization)
- Rh* blocked from activating Transducin
= Rhodopsin Kinase : phosphorylates Rh2* (GRK) at THR and SER or C-terminus, causing Arrestin to bind
=Transducin (GTPase) can’t bind to Rh* - GTP-> GDP causing the a-subunit to dissociate from the PDE6 back the b and y
- GC: decreased Ca+ causes GTP-> cGMP ,High cGMP open Na+ channels
Retinal vs Retinol and Retinoic acid
Retinal= vision protein for retina
Retinol and Retinoic Acid= for health of epithelial cells, cornea, and conjunctiva, t-cells, reproductive health
Vitamin A disorders
Effect the cornea Can cause XEROPHTHALMIA (dry eye syndrome): night blindness, conjunctival xerosis.... BITOT’S SPOTS: (keratin debris buildup in the conjunctiva): foamy in appearance Growth impairment Immune impairment Dry skin Lung problems Follicular Hyperkerarosis
EXCESS VIT A: liver toxicity and joint pain
VIT A when pregnant in the Accutane form = birth defects like cleft plate
Golden Rice
Rice that has genetically been engineered to have FORTIFIED B-CAROTENE which makes VIT A and grown in underserved countries
Beta-Carotene
->Rential -> Retinol
Foods with VIT A
- Carrots: night blindness
- Leafy greens : Xerophthalmia
- Sweet Potatoes: Keratinization of epithelium (GI + Resp)
- Squash: Dry Scaly skin
- Broccoli: AMD
6: Animal Products: Preventable blindness in children
