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Neuroendocrine Test Three > Biochemistry of Visual Systems Dr. Kinde > Flashcards

Biochemistry of Visual Systems Dr. Kinde Flashcards

1
Q

This cell has rhodopsin and high sensitivity with a low spatial resolution. It can respond to one photon. What is it?

A

Rods

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2
Q

This cell has three opsins and low sensitivity with high spatial resolution. It will respond to 100 photons. What is it?

A

Cones

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3
Q

What are the similarities between rods and cones?j

A

Both have an inner segment, outer segment and a synaptic terminal

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4
Q

Describe why rods have high sensitivity.

A
  • Many rods can converge onto one bipolar cell which will contact one ganglion cell
    • High convergence for high sensitivity but low resolution
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5
Q

Descsribe why cones have high resolution

A
  • One cone converges on only one bipolar cell which connects to one ganglion cell
    • allows for high resolution but low sensitivity
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6
Q

What is found in the GPCR system of the disc membranes of the outer segments?

A
  • Opsins
  • Tranducin (the G protein)
  • cGMP phosphodiesterase (effector protein- produces GMP)
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7
Q

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)

A
  • 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
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8
Q

Beta Arrestin?

A
  • Desensitization protein it allows for signal termination by blocking interaction of rhodopsin with transducin
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9
Q

Rhodopsin kinase?

A

Desensitization protein that phosphorylates rhodopsin which is the first step in signal termination

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10
Q

In the dark what happens to photoreceptors?

A

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
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11
Q

In the light what happens to photoreceptors?

A

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
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12
Q

Describe the structure of Rhodopsin and significance of a shiff base

A
  • 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
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13
Q

What happens to 11-cis-retinal when it reacts with photons?

A

Photon induced isomerization occurs

  • 11-cis-retinal isomerizes to 11-trans-retinal
  • Not ligand binding but energy induced
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14
Q

What chromosomes can you find the opsin proteins for Rods, blue, red, and green?

A
  • Rods: chromosome 3
  • Blue 7
  • Red and Green are X chromosome
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15
Q

Describe the signal transduction process in the outer membrane of a disc in a rod in presence of light.

A
  • 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
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16
Q

How does signal termination occur?

A
  • 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
17
Q

How does low light affect cGMP Na and Ca?

A

Light causes low cGMP which causes closure of the Na Ca channels reduing intracellular sodium and calcium. Low calcium levels induce recovery

18
Q

what is the role of Calcium?

A
  • 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

19
Q

Where is Retinal produced?

A

In the retina from vitamin A from the dietary pro-vitamin A carotenoids

20
Q

What are the 3 vitamin A structures?

A
  • 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
21
Q

What is the most important nutritional disorder with respect to the cornea?

A

Vitamin A deficiency. It is typically seen in developing nations and it can increase the likelihood of dying from infections

22
Q

What is Xeropthalmia?

A
  • Abnormal dryness of conjunctivaa and cornea usually associated with vitamin A deficiency
  • This is the second most prevalent nutritional disorder after protein calorie malnutrition
23
Q

Bitot spots?

A

Build up of keratin superficially in ocnjunctiva usually foamy

24
Q

What is accutane?

A
  • Metabolic derivative of retinal used to treat acne
  • Caused birth defects on children whose mothers used it while pregnant
25
Q

How is 11-cis-retinal regenerated? (generally)

A
  • 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
26
Q

What happens in the rod cell in the retinoid cycle? (This is the first steps in the retinol cycle)

A
  • 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
27
Q

What happens in the retinoid cycle within the RPE? (Second portion of retinoid cycle)

A
  • 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
28
Q

What occurs if there is a dysfunction in LRAT and RPE65

A

Retinitis pigmentosa

Recessively inherited

29
Q

ABC transporter dysfunction

A

causes build up of trans-retinal within the membrane compromising the health of photoreceptor cells

30
Q

Retinitis pigmentosa?

A
  • 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
31
Q

Macular Degeneration symptoms, risk factors, causes?

A
  • 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
32
Q

LRAT function?

A

Links all trans retinol to phosphatidyl choline in the membrane to generate all trans retinyl esters within the RPE

Neuroendocrine Test Three (19 decks)

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