354 Molecular Basis of Vision /1 9 : 2 



of vitamin A x (or retinene), there are 2 4 or 16 different isomers which 

 can be drawn with pencil and paper. Only one of these isomers is 

 physiologically active. 



Essentially, one may regard the visual process as the splitting of 

 retinene from opsin and then the resynthesis of rhodopsin, as shown in 

 Figure 2. Unfortunately, this is a gross oversimplification. For if the 

 usual form of vitamin A is converted to retinene, it does not react with 

 opsin at all. This is because the common vitamin A is the all-trans 

 isomer. If retinene is split from rhodopsin, it is also the all-trans 

 isomer and will not recombine. Chemical methods can show that the 

 active retinene is a mono-cis compound but cannot distinguish between 

 the four possible isomers having the cis configuration at the 7-8, 9-10, 

 11-12, and 13-14 positions, respectively. On the basis of a study of the 



1[Rhodopsiny^ Afhoton, hv] 

 IDark J 



Biochemical 

 Energy R e tinene_ 



Figure 2. Simplified version of the visual cycle of rhodopsin. 



actual dimensional configurations, Pauling predicted that the only 

 four stable isomers should be the all-trans, 9-cis, 13-cis, and 9-13 di-cis. 

 Of these, only the 9-cis isomer reacts with opsin, and, although forming 

 a photosensitive pigment, does not form rhodopsin. Thus, retinene 

 cannot be one of the more probable forms. 



The other mono-cis isomers, 7-8 and 11-12, are hindered forms. 

 The interaction between different parts of the molecule twists the long 

 side chain and the ring, distorting the normal planar form. Of these 

 two hindered forms, the isomer with the cis bond at the 11-12 position 

 is less hindered and so is more probable for the active form, which is 

 called neoretinene b or retinene \. 



The plane projection of the 11-12 cis compound is illustrated in 

 Figure 3. This compound possesses a large steric hindrance between 

 13-CH 3 and the 10-H. The 7-8 cis compound possesses a still stronger 

 hindrance between the 9-CH 3 and the 1- and 5-CH 3 groups. The con- 

 version from the all-trans form of vitamin A aldehyde to neoretinene b 

 occurs in the presence of iodine and light. It is believed to occur also 

 within the retina where the conversion is enzymatically catalyzed. 



There is another type of enzyme within the retina (and almost all 

 other body tissues for that matter) which is known as alcohol dehydro- 

 genase (abbreviated ADH) . This enzyme interacts with the visual cycle 



