Rhodopsin-cycle

The molecular mechanism through which vitamin A functions in visual system is known as Rhodopsin cycle or Wald s visual cycle for which George Wald was awarded Nobel Prize. 

Grignolo A, Orzalesi N, Calabria GA. Studies on the line structure and the rhodopsin cycle of the rabbit retina in experimental degeneration induced by sodium iodate. Exp Eye Res 1966 5 86-97. 

Fig. 4.18 The rhodopsin cycle. The bleaching of rhodopsin yields all-trans retinene (now more currently indicated as retinal), which must be isomerized to neoretinene b before it can regenerate the visual pigment. Alternatively, having been reduced to all trans vitamin A, the latter in turn must be isomerized to neovitamin Ab before it takes part in rhodopsin synthesis. Rod vision thus depends on the continuous stereoisomerization of all-trans retinene or vitamin A, or on the continuous replacement of these substances by new supplies of vitamin Ab from external sources (adapted from [196, 197])...

Erom this point of view the retinal changes are of particular interest. While phytanic acid could well play an (unfavorable) role in the rhodopsine cycle (Wald 1960, Baum et al. 1965), in the majority of patients with pigmentary retinitis this change develops in the absence of phytanic acid storage, either as a disease of its own or during the course of other disorders such as a-beta-lipoproteinemia (see page 382). 

The effect of receptor stimulation is thus to catalyze a reaction cycle. This leads to considerable amplification of the initial signal. For example, in the process of visual excitation, the photoisomerization of one rhodopsin molecule leads to the activation of approximately 500 to 1000 transdudn (Gt) molecules, each of which in turn catalyzes the hydrolysis of many hundreds of cyclic guanosine monophosphate (cGMP) molecules by phosphodiesterase. Amplification in the adenylate cyclase cascade is less but still substantial each ligand-bound P-adrenoceptor activates approximately 10 to 20 Gs molecules, each of which in turn catalyzes the production of hundreds of cyclic adenosine monophosphate (cAMP) molecules by adenylate cyclase. 

Figure 12.5. Cycle of reactions involved in the bleaching of rhodopsin by light and subsequent dark restoration.

The interphotoreceptor retinoid-binding protein (Borst et al., 1989) functions in the regeneration of rhodopsin in the mammalian visual cycle. It is exclusive to vertebrates yet contains a repeated structure that has been found singly in bacterial and plant tail-specific proteases (TSPc) (Silber et al., 1992) and the archaeal tricorn protease (Tamura et al., 1996). The eukaryotic homologs of TSPc are likely to be inactive as... 

Figure 15.11 The biochemical reactions that result in the conversion of trans-retinal to ds-retinal, to continue the detection of light To continue the process, trans-retinal must be converted back to c/s-retinal. This is achieved in three reactions a dehydrogenase converts trans-retinal to trans-retinol an isomerase converts the trans-retinol to c/s-retinol and another dehydrogenase converts c/s-retinol to c/s-retinal. To ensure the process proceeds in a clockwise direction (i.e. the process does not reverse) the two dehydrogenases are separated. The trans-retinal dehydrogenase is present in the photoreceptor cell where it catalyses the conversion of trans-retinal to trans-retinol which is released into the interstitial space, from where it is taken up by an epithelial cell. Here it is isomerised to c/s-retinol and the same dehydrogenase catalyses its conversion back to c/s-retinal. This is released by the epithelial cell into the interstitial space from where it is taken up by the photoreceptor cell. This c/s-retinal then associates with the protein opsin to produce the light-sensitive rhodopsin to initiate another cycle. The division of labour between the two cells may be necessary to provide different NADH/NAD concentration ratios in the two cells. A high ratio is necessary in the photoreceptor cell to favour reduction of retinal and a low ration in the epithelial cell for the oxidation reaction (Appendix 9.7).

Proton gradients can be built up in various ways. A very unusual type is represented by bacteriorhodopsin (1), a light-driven proton pump that various bacteria use to produce energy. As with rhodopsin in the eye, the light-sensitive component used here is covalently bound retinal (see p. 358). In photosynthesis (see p. 130), reduced plastoquinone (QH2) transports protons, as well as electrons, through the membrane (Q cycle, 2). The formation of the proton gradient by the respiratory chain is also coupled to redox processes (see p. 140). In complex III, a Q,cycle is responsible for proton translocation (not shown). In cytochrome c oxidase (complex IV, 3), trans-... 

Slowly, arrestin dissociates, rhodopsin is dephosphorylated, and all-frares-retinal is replaced with 11-cis-retinal. Rhodopsin is ready for another phototransduction cycle. 

Retinol A. can be enzymically formed from retinoic acid. B. is transported from the intestine to the liver in chylomicrons. C. is the light-absorbing portion of rhodopsin. D. is phosphorylated and dephosphorylated during the visual cycle. E. mediates most of the actions of the retinoids. Correct answer = B. Retinyf esters are incorporated into chylomicrons. Retinoic acid cannot be reduced to retinol. Retinal, the aldehyde form of retinol, is the chromophore for rhodopsin. Retinal is photoisomerized during the visual cycle. Retinoic acid, not retinol, is the most important retinoid. 

I and II. At very low temperatures a transient form photorhodopsin with a wavelength maximum at 580 nm may precede bathorhodopsin.461b,501-502a Furthermore, nanosecond photolysis of rhodopsin has revealed a blue-shifted intermediate that follows bathorhodopsin within 40 ns and decays into lumirhodopsin.500,503,504 The overall result is the light-induced isomerization of the bound 11-czs-retinal to all-fraus-retinal (Eq. 23-38) and free opsin. Tire free opsin can then combine with a new molecule of 11-czs-retinal to complete the photochemical cycle. 

Figure 23-43 The light-activated transducin cycle. In step a photoexcited rhodopsin (R ) binds the GDP complex of the heterotrimeric transducin (T ). After GDP—GTP exchange (step b) the activated transducin T GTP reacts with the inhibited phosphodiesterase (PDEapY2) to release the activated phosphodiesterase (PDEap). Based on scheme by Stryer528 and other information.

Sensory rhodopsin II (SRII, also called phobo-rhodopsin) is specialized for repellant phototaxis.5913 Blue light converts SRII487 in < 1 ms to UV-absorbing SRII360. It decays in 100 ms to SRn5/W) which reverts to the initial SRII487 in 0.5 s. The cycle is accompanied by swimming reversals that result in a repellent... 

There ensues a series of dark reactions or conformational changes that have the effect of greatly activating the imine linkage of the all-frans-rhodopsin towards hydrolysis. On hydrolysis, all-frawj-retina] is released and is unable to recombine with opsin until it is reconverted to the 11-cis isomer. The trans-to-cis rearrangement is a thermal rather than a photochemical reaction and is catalyzed by the enzyme retinal isomerase. The cycle of reactions is summarized in Figure 28-13. 

Guy, P. M., Koland, J. G., and Cerione, R. A. (1990). Rhodopsin-stimulated activation-deactivation cycle of transducin Kinetics of the intrinsic fluorescence response of the alpha subunit. Biochemistry 29, 6954-6964. 

Despite the fundamental importance of receptor-catalyzed G protein activation in cellular signaling, relatively little is known about this process as compared to the other regulatory events in the G protein cycle. Crystal structures of inactive rhodopsin and G protein heterotrimers provide the structural context for the meaningful interpretation of the results of the numerous biochemical and biophysical studies described in the preceding sections. Enough data has been accumulated to begin to develop rudimentary models of the receptor-G protein complex that meet some of... 

Rhodopsin, visual cycle, night vision Blood clotting factors II, VII, IX, and X Calcium and phosphorus homeostasis Antioxidant, glutathione oxidase... 

A number of geometric isomers of retinol exist because of the possible cis-trans configurations around the double bonds in the side chain. Fish liver oils contain mixtures of the stereoisomers synthetic retinol is the all-trans isomer. Interconversion between isomers readily takes place in the body. In the visual cycle, the reaction between retinal (vitamin A aldehyde) and opsin to form rhodopsin only occurs with the 11 -cis isomer. 

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