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NeuroEndo Exam 3 > Biochemistry of Visual System (Kinde) > Flashcards

Biochemistry of Visual System (Kinde) Flashcards

1
Q

Rods Characteristic

A
  • 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)
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2
Q

Cones Characteristics

A
  • 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)
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3
Q

Explain what happens in the dark/default state in photoreceptors

A

Default = Depolarized = Cell is always active and releases Glutamate (inhibitory NTs)

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4
Q

Explain what happens to photoreceptos in the presence of light

A

Light = cell hyperpolarized = decrease in presence of Glutamate

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5
Q

What is Rhodopsin

A

A 7 transmembrane protein receptor found in Rods that detects light

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6
Q

What are the structural features of Rhodopsin

A

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.

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7
Q

How much light does the protonated schiff base absorb

A

> 440 nm

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8
Q

What happens to Rhodopsin in the presence of light

A

11-cis-Retinal isomerizes to all-trans-retinal causing a conformational change in Rhodospin

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9
Q

What is Retinal derived from

A

Vitamin A

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10
Q

What are the opsin’s found in Cones?

A

Blue, red & green opsin

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11
Q

What is the absorption maxima & chromosome # of the Blue opsin protein

A

420 nm

Chromosome 7

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12
Q

What is the absorption maxima & chromosome # of the Red opsin protein

A

560 nm

X chromosome

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13
Q

What is absorption maxima & chromosome # of the Green opsin protein

A

530 nm

X chromosome

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14
Q

Can AMAB individuals affected with red/green color blindess pass the trait of to their offsprings?

Why?

A

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.

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15
Q

Can unaffected AFAB carriers pass R/G color blindess trait to their offsprings?

If so, which gender and why?

A

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

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16
Q

Explain the signal transduction pathway for photoreceptors

A
  1. Presence of light causes isomerization of 11-cis-retinal –> all-trans-retinal leading to a conformational chage in Rhodopsin, activating it.
  2. 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.
  3. Transducin-α binds to phosphodiesterase (PDE) inhibitory γ subunit, actiavting PDE.
  4. 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.
  5. Decreased intracellular Ca2+ leads to a decrease in the amount of Glutamate being realeased by the cell (vesicle fusion decreases).
17
Q

Function of Guanulyl Cyclase (GC) and how is it regulated

A
  1. GC is the enzyme that produces cGMP from GTP.
  2. 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 .
18
Q

How are the photoreceptor signals terminated

A
  1. Rhodopsin kinase phosphorylates the C-terminus of Rhodopsin at the Thr & Ser residues, allowing Arrestin to bind which prevents interactions with transducin.
  2. Rapid hydrolysis of GTP to GDP causes dissociation of Transducin-α subunit from PDE & reassociation with the β and γ subunits.
  3. Guanylate cylase synthesizies cGMP, elevating cGMP levels which re-open cGMP-gated Na+ channels depolarizing the cell.
19
Q

What is the role of Ca2+ in the signal transduction process in rod and cone cells

A

INDUCE RECOVERY

Ca2+ govern the rate by which the system is restored by controlling the rate of cGMP synthesis by Guanylyl Cyclase (GC)

20
Q

What are the 3 Vitamin A structures

A

Retinol (Hydroxyl FG)

Retinoic Acid (Carboxyl FG)

Retinal (Aldehyde FG)

21
Q

Vitamin A deficiency

A

The most important nutritional disorder with respect to the cornea & increases the likelihood of dying from infections

22
Q

What are some disorders associated with Vitamin A

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

23
Q

What are the effects of kids exposed to Isotretinoin/Accutane (Vitamin A derivative) in the womb

A

Cleft palates & heart abnormalities

24
Q

What is the first genetically designed biofortified food that was created to treat Vitamin A deficiency

A

Golden Rice

25
Q

How is 11-cis-retinal regenerated

A

Through a series of enzymatic steps in two cellular systems:

  1. Photoreceptors (rods/cones)
  2. Retinal pigmented epithelium (RPE)
26
Q

What is the function of ABC transporters in the retinoid cycle

A

ABC transporters move all-trans-retinal from the photoreceptors into the cytoplasm

Clearance of 11-trans-retinal from photoreceptors

27
Q

How is all-trans-retinal converted to all-trans-retinol

A

all-trans retinol dehydrogenase (aRDH)

28
Q

What transporter facicilates movement between the photoreceptor and retinal pigmented epithelium (RPE) in the Retinoid cycle

A

inter-photoreceptor retinoid binding protein (iRBP)

29
Q

What is the function of LRAT

A

Converts all-trans-retinol –> all-trans-retinyl esters

30
Q

What is the function of RPE65

A

Converts all-trans-retinyl ester –> 11-cis-retinol bound to CRALBP

CRALBP = cellular retinaldehyde binding protein

31
Q

What causes Retinitis Pigmentosa

A

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

32
Q

What are the effects of Retinitis Pigmentosa

A

Decreased night vision & peripheral vision

33
Q

Mutations in what protein are known to cause macular degeneration and related disorders associated with severe central vision loss

A

ABC transporters

34
Q

Degeneration of the macula in the retina results in what

A

Loss of central field vision

35
Q

What are some risk factors for Macular degeneration

A

Advance age, especially over 70

History of smoking with past 20 years

Dietary factors

Obesity

Caucasian

36
Q

Explain the 11-cis-retinal regeneration step that occurs in the photoreceptors

A
  1. Release of all-trans-retinal from opsin
  2. Transport of all-trans-retinal to the cytoplasm by ABC transporter
  3. Enzymatic reduction of all-trans-retinal to all-trans-retinol (Vitamin A) by all-trans-retinol dehydrogenase (at-RDH)
  4. Transport of all-trans-retinol to RPE by interphotoreceptor retinoid binding protein (iRBP)
37
Q

Explain the 11-cis-retinal regeneration step that occurs in the Retinal pigmented epithelium (RPE)

A
  1. all-trans-retinol bound to retinoid binding protein (CRBP) undergoes esterification to all-trans-retinyl by lecithin retinol acyl transferase (LRAT)
  2. all-trans-retinyl is converted to 11-cis-retinol by RPE65
  3. 11-cis-retinol is oxidized to 11-cis-retinal by 11-cis-RDH
  4. iRBP transports 11-cis-retinal to the photoreceptors then a colavent schiff base attachment forms a functional rhodospin

NeuroEndo Exam 3 (16 decks)

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