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Neuroscience I > Biochemistry of Vision (Dr. Seidler) TEST 2 > Flashcards

Biochemistry of Vision (Dr. Seidler) TEST 2 Flashcards

1
Q

Neuronal Organization of Retina

A

FIVE LAYERS:

  • Outer Nuclear
  • Plexiform
  • Inner Nuclear
  • Plexiform
  • Ganglion Cell

THREE CELL LAYERS:

1) Photoreceptors
2) Interneurons (Bipolar, Horizontal, and Amacrine Cells)
3) Ganglion Cells

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2
Q

Retinal Circuits

A

Processing of Visual Signals:

- Photoreceptors —> Interneurons —> Ganglion Cells

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3
Q

Ganglion Cells

A
  • Output Cells of the Retina
  • Axons form OPTIC NERVE
  • Project to the Brain
  • Information transmitted by ACTION POTENTIALS
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4
Q

Photoreceptors

A

1) RODS (For NIGHT Vision):
- RHODOPSIN (Cannot Detect Color)
- HIGH Sensitivity and LOW Spatial Resolution

**IN THE DARK: The Na+ Channels are OPEN and the Cell is DEPOLARIZED

**IN THE LIGHT: The Na+ Channels are CLOSED and the Cell is HYPERPOLARIZED

2) CONES (For COLOR Detection):
- Three OPSINS (Red, Green, Blue)
- LOW Sensitivity and HIGH Spatial Resolution

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5
Q

Outer Segment

A
  • Rods are ELONGATED structures; the OUTER SEGMENT is SPECIALIZED for PHOTORECEPTOR.
  • The Outer Segment contains a Stack of about 1000 Discs, which are MEMBRANE-ENCLOSED Sacs DENSELY PACKED with Photoreceptor Molecules.
  • The PHOTORECEPTOR Molecule in RODS is RHODOPSIN, which consists of the Protein OPSIN linked to 11- CIS- RETINAL, a Prothetic Group
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6
Q

Proteins of the Outer Segment

A

1) DISC MEMBRANE:
- GPCR System:
a) Rhodopsin- Photoreceptor

b) Transducer- Trimeric G Protein that has 3 Subunits (Alpha, Beta, Gamma)
c) Phosphodiesterase- Breaks down cGMP (LIGHT)

2) SURFACE MEMBRANE:
a) cGMP Gated Na+ Channel (Ca2+ Leak Channel)
- IN the DARK the Channels are OPEN and the cGMP will be HIGH

b) Na+/ Ca2+ Exchanger (Ca2+ continues out after Illumination
c) Guanylate Cyclase (GTP —> cGMP + PPi)

3) ANCILLARY PROTEINS:
- Beta ARRESTIN (Arrests the Rhodopsin)
- Rhodopsin Kinase

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7
Q

Disc Shedding

A
  • Continuous situation where the TIPS of the RODS and CONES are Cut OFF!
  • ** Retinal Pigmented Epithelium (In the VERY Back of the Retina)
  • The ROD CELL is partially Plugged into this Epithelium
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8
Q

The 7TM Receptor

A
  • Has an N and C Terminus
  • Have 7 Transmembrane Helices
  • **RHODOPSIN is a Member of this Family.
  • It contains a VITAMIN A derived CoFactor in the Middle
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9
Q

Structure of Rhodopsin and the B2- Adrenergic Receptor

A
  • The Resemblance in the OVERALL Architecture of BOTH Receptors and the Similar LOCATIONS of the Rhodopsin Ligand 11- CIS RETINAL and the Beta2- AR Blocker CARAZOLOL!!!!!
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10
Q

Retinal Lysine Linkage

A
  • Retinal is LINKED to Lysine 296 in OPSIN by a SCHIFF-BASE LINKAGE
  • IN the RESTING STATE of Rhodopsin, this Schiff Base is PROTONATED
  • The Aldehyde group of 11- Cid- Retinal forms a Schiff Base with he Epsilon- Amino Group of the Lysin residue 296, which lies in the CENTER of the Seventh Transmembrane Helix
  • FREE Retinal ABSORBS Maximally at 370 nm, and its UNPROTONATED Schiff-Base ADDUCT Absorbs at 380 nm, whereas the PRONATED Schiff Base absorbs at 440 nm or Longer Wavelengths
  • Thus, the 500nm Absorption Maximum for Rhodopsin STRONGLY suggests that the Schiff Base is PROTONATED; additional interactions with Opsin Shift the Absorption Maximum Farther toward the RED
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11
Q

Evolutionary Relationships among Visual Pigments

A
  • Visual Pigments have evolved by GENE DUPLICATION along different Branches of the Animal Evolutionary Tree. The Branch lengths of the “Trees” correspond to the Percentage of Amino Acid DIVERGENCE

***CHangeing the Way the Protein reacts with the 11- Cis- Retinal

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12
Q

Photoreceptor Proteins

A

1) ROD OPSIN:
- Broad Spectrum (500 nm)
- Chromosome: 3

2) BLUE OPSIN:
- 420 nm
- Chromosome: 7

3) RED OPSIN:
- 560 nm
- Chromosome: X!!!!!!

4) GREEN OPSIN:
- 530 nm
- Chromosome: X!!!!!!

**Red and Green are sitting on the X Chromosome and sitting close to one another

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13
Q

Recombination Pathways that lead to Color Blindness

A
  • Rearrangements in the course of DNA Replication may lead to:
    1) The LOSS of Visual Pigment Genes

2) The FORMATION of Hybrid Pigment genes that ENCODE Photoreceptors with Anomalous Absorption Spectra
- Because the Amino Acids most important for determine absorption Spectra are in the CARBOXYL-TERMINAL half of each Photoreceptor Protein, the part of the Gene that encodes this region most STRONGLY AFFECTS the ABSORPTION Characteristics of HYBRID Receptors

For the 7TM Protein:
- Open Circles correspond to Identical Residues, whereas filled Circles Mark residues that are Different. The differences shown by the Three Black Positions are responsible for MOST of the DIFFERENCE in ABSORPTION SPECTRUM

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14
Q

Macular Degeneration

A

THE PERFECT STORM:

  • High Respiratory Quotient: HIGH O2 FLUX
  • High LIPID Content
  • UV Rays

MACULAR CAROTENOIDS (Xanthophylls):

  • Lutein
  • Zeaxanthin
  • These are Antioxidants*
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15
Q

Dietary Considerations

A

RDA (UL: 3,000 mg)

  • F: 700 mg
  • M: 900 mg

FOOD Sources:

  • Carrots
  • Dark Green and Leafy Vegetables
  • Sweet Potatoes
  • Squash
  • Broccoli

CONSEQUENCES of DEFICIENCY:

  • NIGHT BLINDNESS
  • Xerophthalmia
  • Keratinization of Epithelium in GI, Respiratory, and Genitourinary Tract
  • Skin becomes DRY and SCALY

*****Ingested Beta-Carotene is converted into RETINOL by Dioxygenase (Intestinal Mucosa)

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16
Q

Transport of Retinol in Blood Plasma

A
  • Retinol is transported through the blood by RBP!!!
17
Q

Retinoid Cycle

A

1) IN THE ROD CELL:
- 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)

2) In the Retinal Pigmented Epithelium (RPE):
- Uptake into RPE

  • Translocation to ER
  • Esterification of ALL-TRANS- RETINYL ESTER by LECITHIN RETINOL ACYL TRANSFERASE (LRAT)
  • Conversion of 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)

3) IN the ROD CELL:
- Uptake of 11-CIS- RETINAL into Rod Cell

  • Covalent Attachment (Schiff Base) to OPSIN forming a Functional Rhodopsin
18
Q

Energy Transduction (GPCR Complex)

A

1) Visual Pigment (Rhodopsin)
2) G Protein Transduction
3) cGMP to cGMP- Gated Channel to allow Na+ INFLUX

***A Photon of Light causes a conformational change around the Double Bond of OPSIN!!!!

***Change in Configuration changes the CONFIRMATION

*** Rhodopsin —> Meta II —> Meta II G alpha CT2 leads to a very large number of G Proteins being activated

19
Q

Signal Termination

A
  • Signal transduction by the 7TM Receptor is Halted by:
    1) DISSOCIATION of the SIGNAL Molecules from the Receptor

2) Phosphorylation of the Cytoplasmic C Terminal Tail of the Receptor and the subsequent Binding of BETA-ARRESTIN
- The Visual System responds to Changes in Light and Color within a few Milliseconds, quickly enough that we are able to PERCEIVE continuous Motion at nearly 1000 frames per second
- To achieve a RAPID RESPONSE, the Signal must also be TERMINATED RAPIDLY and the System must be RETUNED to its INITIAL STATE
1) First, ACTIVATED Rhodopsin must be BLOCKED from continuing to activate TRANSDUCIN
- Rhodopsin KINASE catalyzed the Phosphorylation of the Carboxyl Terminus of R* at MULTIPLE Serine and Threonine Residues.
2) Second, ARRESTIN, which is an Inhibitory Protein then binds Phosphorylated R* and prevents additional Interaction with Transducin!!!!!

20
Q

Light Induced Lowering of Ca2+ levels coordinates Recovery

A
  • Calcium ion plays an Essential Role in controlling GUANYLATE CYCLASE because it markedly INHIBITS the activity of the Enzyme
  • In the DARK, Ca2+ as well as Na+ enter the ROD Outer Segment through the cGMP-Gated Channels.
  • Calcium Ion INFLUX is BALANCED by its EFFLUX through an Exchanger, a Transport System that uses the Thermodynamically Favorable FLOW of FOUR Na+ ions into the Cell and one K+ ion out of the Cell to Extrude one Ca2+ ion.
  • After Illumination, the ENTRY of Ca2+ through the cGMP-Gated Channels STOPS, but its EXPORT through the Exchanger continues.
  • Thus, the Cytoplasmic Ca2+ LEVEL DROPS from 500 nM to 50 nM after ILLUMINATION
  • This drop markedly stimulates GUANYLATE CYCLASE, rapidly restoring the Concentration of cGMP to REOPEN the cGMP- GATED CHANNELS!!!!!!!!
21
Q

Amplifications

A

1) One RHODOPSIN Absorbs ONE Photon
2) 500 TRANSDUCIN Molecules are Activated
3) 500 Phosphodiesterase Molecules are ACTIVATED
4) 10^5 cGMP Molecules are HYDROLYZED
5) 250 Na+ Channels CLOSE
6) 10^6 to 10^7 Na+ Ions/ sec are prevented for a period of about 1 Sec
7) Rod Cell Membrane is HYPERPOLARIZED by 1 mV!!!!!

Neuroscience I (18 decks)

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