The Chemistry of Vision

Vision, our ability to perceive light, is the result of an isomerization reactioa Our eyes contain millions of cells called rods that are packed with rhodopsin, an 11-cw-retinal molecule 

2 Identify each reaction as addition, substitution, elimination, or isomerization. 

Cis-trans isomerism piays a key role in the process of vision. The rod ceiis in the retina of the eye contain a red, light-sensitive pigment called rhodopsin. This pigment consists of the protein opsin combined at its active site with 1 1 -c/s-retinal. When visible light with the appropriate energy is absorbed by rhodopsin, the complexed c/s-retinal is isomerized to the trans isomer. This process is fantastically fast, occurring in only 

The trans-retinal complex with opsin (called metarho-dopsin-ll) is less stable than the c/s-retinal complex, and it dissociates into opsin and frans-retinal. This change in geometry triggers a response in the rod nerve cells, which is transmitted to the brain and perceived as vision. 

If this were all that happened, we would be able to see for only a few moments, because all of the 11 -c/s-retinal present in the rod cells would be quickly consumed. Fortunately, the enzyme retinal isomerase, in the presence of light, converts the traws-retinal back to the 11 -cis isomer so that the cycle can be repeated. Calcium ions in the cell and its membrane control how fast the visual system recovers after exposure to light. They also mediate the way in which cells adapt to various 

Electrostatic potential map of ethylene showing accessibility of pi electrons (red) to attack by electron-seeking reagents. 

But before we consider reactions at the double bond, let us examine an important result of the restricted rotation around double bonds. 

The light-sensitive compound in rods is called rhodopsin. In 1952, Nobel Laureate George Wald (Harvard University) and his co-workers showed that the chromophore in rhodopsin is the conjugated polyunsaturated system of 11-cw-retinal. Rhodopsin is produced by a chemical reaction between 11 -ch-retinal and a protein called opsin. 

The conjugated Tt system fits precisely into an internal cavity of opsin and absorbs light over a broad region of the visible spectrum (400—600 nm). Sources of 11-CM-retinal include vitamin A and (3-carotene. A vitamin A deficiency causes night bUndness, while a diet rich in 3-carotene can improve vision. 

Wald demonstrated that rhodopsin made from 11-c -retinal gave the same photoproduct as rhodopsin made from 9-CM-retinal. He concluded that the primary photochemical reaction must be a cis-trans isomerization. 

Further evidence supporting this photoisomerization step came from Koji Nakanishi s work at Columbia University. Nakanishi s group synthesized an analogue of 11-af-retinal, in which the cis double bond was incorporated in a seven-membered ring, thereby preventing it from isomerizing to the trans configuration. 

Recall from Section 8.4 that rings of fewer than eight carbon atoms cannot accommodate a trans it bond at room temperature. When Nakanishi s analogue binds with opsin, the product is similar to rhodopsin but is unable to isomerize under the influence of light. When Nakanishi s analogue was administered to rats, their vision was severely impaired. Based on these and other convincing pieces of evidence, it is widely accepted that the first step in the chemistry of vision is a photoisomerization reaction. 

---

FIGURE 17 11 Imine formation between the aldehyde function of 11 as retinal and an ammo group of a protein (opsin) is involved in the chemistry of vision The numbering scheme in retinal is specifically developed for carotenes and related compounds... 

Carotenoids absorb visible light (Section 13 21) and dissipate its energy as heat thereby protecting the organism from any potentially harmful effects associated with sunlight induced photochemistry They are also indirectly involved m the chemistry of vision owing to the fact that p carotene is the biosynthetic precursor of vitamin A also known as retinol a key substance m the visual process... 

Retinoid acid is a transcription factor. Retinoids play significant roles in dermatology, in the prevention of some cancers, and in the chemistry of vision. Consequently, many works have been dedicated to fluorinated analogues of retinoids. 

Special Issue on the Chemistry of Vision, Accts. Chem. Res. 8, 81-112 (1975). 

Cis-trans isomerization is an important step in the chemistry of vision, for example, the light-initiated, enzyme-catalyzed isomerization of cis to frans-retinal. 

Beyond its vital importance in the chemistry of vision, cis-trans isomerization offers potential advantages for organized assemblies capable of photoswitching. The latter is frequently a fast process which requires a strictly photochemical... 

The absorption peak of this compound appears at X = 325 nm. This molecule plays an important role in the chemistry of vision. 

One example of this process is found in the chemistry of vision. Ill the rods and cones of the eye, the aldehyde 11 -cis-retinal forms an imine by reaction with an amino group of the protein opsin. Studies have shown that the nitrogen of the imine of the product, called rhodopsin. is protonated. 

Many imines play vital roles in biological systems. A key molecule in the chemistry of vision is the highly conjugated imine rhodopsin, which is synthesized in the rod cells of the eye from 11-cis-retinal (the molecule introducing Chapter 21) and a 1° amine in the protein opsin. 

The role of rhodopsin in the chemistry of vision (Opener, Section 21.11B)... 

CHEMISTRY WORK Carrots. Alkenes, and the Chemistry of Vision 221... 

Vitamin A performs numenius biochemical functions. It promotes the production nf mucus by the basal cells of the epithelium, whereas in its absence keratin can be fonned. Vitamin A performs a function in the biosynthesis of glycogen and some steroids, and increased quantities nf coen/yme Q are found in the livers nf vitamin-deficicnt rats. Significantly. the best-known action of vitamin A is its function in the chemistry of vision. 

Thu molecular mechanism of action of vitamin A in the visual process has been under investigation for many years. Wald in 1(168 and Morton in 1972" characterized this mechanism of action. The chemistry of vision was reviewed comprehensively in Accotmi.t of Clwmical Research (1975) by numerous investigators. These reviews include theoretical studies of the visual chromophorc. characleri/alion of ihfldopsin in synthetic systems, dynamic processes in vertebrate rod visual pigments and their membranes, and the dynamics of the visual protein opsin. ""... 

This process is a key step in the chemistry of vision. Although free retinal (in the form shown to the left of the arrow) has an absorption maximum at 376 nm, in the ultraviolet region of the spectrum this absorption shifts into the visible range when the retinal is bound in a protein, as it is in the eye. 

Diagrammatic representation of bovine rhodopsin embedded in the disk membrane. Only three of the seven a-helical segments are shown. The only point of attachment between retinaldehyde and opsin is the indicated aldimine bond. [Modified and reproduced, with permission, from D, F. O Brien, The chemistry of vision. Science 218,961 (1982), 1982 by the American Association for the Advancement of Science.]... 

FIGURE 17.8 I mine formation between the aidehyde function of 11-c/s-retinai and an amino group of a protein (opsin) is invoived in the chemistry of vision. The numbering scheme used in retinai is based on one specificaiiy deveioped for carotenes and compounds derived from them. 

---