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Visual Cycle Retinal photoreceptor cells ◼ Contain photoreceptor molecules that respond to particular wavelengths of light ◼ Generate impulses that are sent to the brain through the optic nerve ◼ Vary in their sensitivity to light depending on type and also on the intensity of light they are exposed to Retinal photoreceptors ◼ Two kinds: rods and cones ◼ Rods are responsible for low intensity, (black and white or scotopic) vision ◼ Cones are responsible for high intensity (colour or photopic) vision ◼ There are 100 million rods and 3 million cones in each retina The eye Retinal cells ◼ . The rod cell ◼ . THE ROD CELL ◼ The outer segments of rods and cones have stacks of discs which contain the photoreceptors molecules whiles the inner segments contains numerous large mitochondria. The stacks of discs are formed by the invagination of the plasma membrane. ◼ The photoreceptor molecule for cones is iodopsin whiles that of rods is rhodopsin. The photoreceptor molecules (visual pigments) consist of an opsin (protein moiety) and 11-cis- retinal (chromophore). That is: rhodopsin = scotopsin (opsin) + 11-cis-retinal ◼ iodopsin= photopsin (opsin) + 11-cis-retinal . ◼ . Retinal ◼ . ◼ The protonated Schiff base is the visual pigment. Sources of vitamin A ◼ Fish liver ◼ Mammalian & chicken livers ◼ Eggs ◼ Whole milk ◼ Carotene from plants ◼ Yellow vegetables ◼ Sweet potatoes Metabolism of vitamin A ◼ . ◼ Retinol (alcohol) is formed from retinal (aldehyde). Retinal can be obtained in two ways: ◼ *from β-carotene through oxidative cleavage catalyzed by the enzyme β-carotene dioxygenase. ◼ *from retinyl esters in the intestinal lumen. ◼ Retinol is then formed from retinal by the enzyme alcohol dehydrogenase by the addition of 2H ions in the form of NADH2 . ◼ . ◼ . The visual cycle ◼ . ◼ . ◼ . The light energy in a photon is converted into atomic motion. Absorption spectrum of rhodopsin ◼ . Absorption spectrum of rhodpsin Absorption spectra Rhodopsin 500 nm Protonated rhodopsin 440 nm Unprotonated 380 nm rhodopsin Free retinal 370 nm Special properties of 11-cis-retinal ◼ It is a polyene containing six alternating single and double bonds ◼ Has a long unsaturated electron network (six alternating single and double bonds). ◼ It is isomerized by light very efficiently ◼ The structural change on isomerization is large Photolysis: intermediates ◼ . The visualPHOTOLYSIS/BLEACHING cycle ◼ . EFFECT OF A LIGHT PULSE ON A ROD CELL Hyperpolarisation of the rod cell membrane ◼ . DARK ADAPTATION LIGHT ADAPTATION Adaptation ◼ . Transmitters in visual excitation 2+ ◼ Ca : On photolysis rod cell [Ca2+] decreases ◼ cGMP: On photolysis rod cell [cGMP] decreases . ◼ . Guanylate cyclase . ◼ . Activation of transducin . ◼ . ◼ . Visual signal transduction ◼ . Hetero-trimeric G-protein R*+G-protein =transducin Light induced lowering of calcium level coordinates recovery ◼ The visual system responds to changes in light and color within a few milliseconds ◼ We are able to perceive continuous motion at nearly 1000 frames per second ◼ To achieve a rapid response the signal must be terminated rapidly and the system returned to its original state Recovery: step 1 ◼ Activated rhodopsin must be blocked from continuing to activate transducin ◼ Rhodopsin kinase catalyses the phosphorylation of the carboxyl terminus of R* at multiple serine and threonine residues ◼ Arrestin, an inhibitory protein then binds phosphorylated R* and prevents additional interaction with transducin: R*PPPArr Recovery: step 2 ◼ The subunit of transducin hydrolyses GTP to GDP ◼ Hydrolysis takes place in less than a second when transducin is bound to the phosphodiesterase ◼ The GDP form of transducin then leaves the phosphodiesterase and reassociates with the subunits and the PDE returns to its inactive state ◼ T-GTP →T-GDP+Pi Recovery: step 3 ◼ The level of cGMP must be raised to re- open the cGMP-gated ion channels Guanylate cyclase⇍Ca2+ GTP→ cGMP + PPi Ca2+ ions control guanylate cyclase activity…..1 2+ + ◼ Ca and Na ions enter the outer rod segment in the dark through cGMP- gated channels 2+ ◼ Ca ion influx is balanced by its efflux through an exchanger + ◼ The exchanger uses influx of four Na ions and efflux of one K+ ion to extrude one Ca2+ . Ca2+ ions control guanylate cyclase activity….2 ◼ After illumination the entry of calcium through the cGMP-gated channels stops but its export through the exchanger continues 2+ ◼ The cytosolic Ca level drops from 500nM to 50nM after illumination ◼ This drop markedly stimulates guanylate cyclase rapidly restoring the concentration of cGMP to re-open the cGMP-gated channels . ◼ . Colour vision ◼ Mediated by three types of cone cells; blue, green and red absorbing photoreceptor cells absorbing maximally at 455, 530, 625nm respectively ◼ All contain the same chromophore: 11- cis-retinal ◼ 11-cis-retinal absorbs maximally at 380 nm . ◼ . Colour vision ◼ Groups on opsin have a large effect on the chromophoric properties of the bound 11-cis-retinal ◼ The properties of a prosthetic group are modulated by its interaction with a protein Colour blindness ◼ Most forms caused by a sex-linked recessive mutation ◼ 1% of men are red-blind and 2% are green- blind ◼ These people lack either the red or green- absorbing photoreceptor molecule or they have an altered pigment with a shifted absorption spectrum Colour blindness ◼ Caused by absence or defect of one kind of cone opsin. ◼ Night blindness is usually caused by deficiency in retinol (Vitamin A). ◼ Colour blindness is caused by an absence or defect of one kind of cone opsin..
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