Thursday, 4-7-Biochemistry Of Vision (Seidler)

Question 1

What are the 3 cell types of the retina?

Answer 1

• photoreceptors
• interneurons (bipolar cells, horizontal cells, amacrine cells)
• ganglion cells

Question 2

List the pathway for the processing of visual signals:

Answer 2

Photoreceptors —> interneurons —> ganglion cells

Question 3

__ are the output cells of the retina whose axons form the optic nerve. They project to the brain and information is transmitted by action potentials

Answer 3

Ganglion cells

Question 4

These photoreceptors are for night vision, have rhodopsin, and have high sensitivity and low spatial resolution

Answer 4

Rods

Question 5

These photoreceptors are for color detection and have 3 opsins (red, green, blue). They have low sensitivity and high spatial resolution

Answer 5

Cones

Question 6

When are Rods depolarized?

Answer 6

In the DARK: Na+ channels open and cell depolarizes

In the LIGHT: Na+ channels close and cell is hyperpolarized

Question 7

The __ segment of rods are specialized for photoreception.

The photoreceptor molecule in rods is __, which consists of the protein opsin linked to 11-cis-retinal, a prosthetic group

Answer 7

Outer

Rhodopsin

Question 8

The disc membrane of the outer segment of the Rods contain a GPCR system. List the components of the GPCR system:

Answer 8

• Rhodopsin: the receptor
• Transducin: Trimeric G protein
• Phosphodiesterase: the effector enzyme

Question 9

What is a homologue to Rhodopsin?

Answer 9

Beta 2-adrenergic receptor

Question 10

What is the ligand for Rhodopsin?

What is the wavelength absorbance of Rhodopsin?

Answer 10

11-cis-retinal

500 nm

Question 11

The 500 nm absorption maximum for rhodopsin strongly suggests that the schiff base is ___

Retinal is linked to this AA by a schiff-base linkage:

Answer 11

Protonated

-Lysine (Lys 296)

Question 12

What is the absorption maxima of the blue opsin protein?

What is the absorption maxima of the red opsin protein?

What is the absorption maxima of the green opsin protein?

Answer 12

420

560

530

Question 13

Describe how color blindness occurs:

Answer 13

• Recombination between genes–> rearrangement in the course of DNA replication may lead to loss of pigment genes
• Recombination within genes –> formation of hybrid pigment genes that encode photoreceptors with anomolous absorption spectra.

Question 14

The macular carotenoids (xanthophylls) include:

Answer 14

• Lutein

- Zeaxanthin

Question 15

What are consequences of vitamin A deficiency?

Answer 15

• Night blindness
• Xerophthalmia
• Keratinization of epithelium in GI, respiratory, and genitourinary tract
• Skin becomes dry and scaly

Question 16

Describe metabolism of ingested beta-carotene:

Answer 16

Beta carotene ———————————-> 2 Retinol

Dioxygenase (intestinal mucosa)

Question 17

How is Retinol transported in the blood plasma?

Answer 17

Retinol bound to RBP (Retinol Binding Protein)

Question 18

Describe the pathway of a single photon of light leading to cell hyperpolarization:

Answer 18

1 rhodopsin absorbs 1 photon –> 500 transducin molecules activated –> 500 phosphodiesterase molecules activated –> 10 to the 5th cGMP molecules hydrolyzed –> 250 Na+ channels close –> 10 to the 6th - 10 to the 7th Na+ ions/sec are prevented for a period of ~1 second –> Rod cell membrane is hyperpolarized by 1 mV

Question 19

Regarding the Retinoid cycle, identify where the following takes place:

-Light-induced change from 11-cis to all-trans –> release of all-trans-retinal from opsin –> enzymatic reduction of all-trans-retinal to all-trans-retinol –> exportation of all-trans-retinol (with help of iRBP)

Answer 19

In the ROD CELL

Question 20

Regarding the Retinoid Cycle, identify where the following takes place:

-Uptake of all-trans-retinol into the retinal pigmented epithelium (RPE) –> translocation to ER –> Esterification to all-trans-retinyl ester by lecithin retinol acyl transferase (LRAT) –> conversion to 11-cis-retinol by isomerohydrolase activity of RPE65 –> Enzymatic oxidation from 11-cis-retinol to 11-cis-retinal by 11-cis RDH –> Exportation of 11-cis-retinal (with help of iRBP)

Answer 20

In the RPE

Question 21

Regarding the Retinoid cycle, identify where the following takes place:

-Uptake of 11-cis-retinal from RPE –> Covalent attachment (Schiff base) to opsin forming a functional rhodopsin

Answer 21

In the ROD CELL

Question 22

List the 5 layers of the retina:

Answer 22

• Outer nuclear
• Plexiform
• Inner nuclear
• Plexiform
• Ganglion cell

Question 23

Infants exposed to ___ in the womb may have birth defects such as cleft palates and heart abnormalities

Answer 23

Isoretinoin

Question 24

___ is a cancer of the blood an BM marked by buildup of immature WBCs (promyelocytes). It is linked to the presence of PML-RARalpha, the product of a fusion betweeen the promyelocytic leukemia (PML) gene and the retinoic acid receptor alpha (RARalpha) gene.

Answer 24

Acute promyelocytic leukemia (APL)

Question 25

PML-RARalpha acts to repress the transcription of certain genes and thus prevent cell differentiation. This results in accumulation of immature promyelocytes. Treatment with ___ relieves PML-RARalphas repression of transcription and thus stimulates differentiation and maturation of promyelocytes and contributes to APL remission

Answer 25

All-trans-retinoic acid