574 IX. CAROTENOIDS AND VITAMINS A 



was added to the four-component system in the dark, a synthesis Avas im- 

 mediately effected in all cases, when the inactive vitamins A were exposed 

 to light in the presence of iodine. This latter procedure has been widely 

 employed by ZechmeisteF^- to produce isomerization of carotenoids; 

 all possible isomers result in the mixture when any single carotenoid is ex- 

 posed to the above treatment. For a further discussion of this effect, the 

 reader is referred to The Lipids, Vol. I, pages 635, 636. 



Although the theory as proposed by Pauling'^^^ limits the number of iso- 

 mers of vitamin A to four, Wald and associates''^^'^^'''^^^ examined five 

 crystalline isomers of retinene, namely all-^rans-retinene, neo-a retinene, 

 neo-6 retinene, iso-a retinene, and iso-& retinene. On incubation with 

 opsin, all-trans retinene and neo-a retinene gave negative results. On the 

 other hand, neo-6 retinene produced a rapid synthesis of rhodopsin, which 

 was indistinguishable from the reaction when the retinene extracted from 

 the retina was the substrate. Iso-a retinene produced about the same 

 amount of pigment as did neo-6 vitamin A, but the rj max. of this new pig- 

 ment A\ as displaced about 13 ni/x ])elow that of neoretinene. Presumably it 

 differs from rhodopsin. This new pigment is now referred to as isorhodop- 

 sin. Although iso-6 retinene was also found to be inactive, it was rapidly 

 isomerized to iso-a retinene by a very short exposure to light; the latter 

 product readily formed isorhodopsin. In spite of the Pauling theory, 

 which would limit the isomers of vitamin A to four, all five products stud- 

 ied by Wald and co-workers''^^ '^-"'^^^ were readily interconvertible, and are 

 believed to be cis-trans isomers. 



In view of the newer information concerning the role of the stereoiso- 

 meric retinenes in rhodopsin formation, Hubbard and Wald^^^ proposed a 

 modification of the rhodopsin cycle, which is pictured in Figure 2. 



According to the above scheme (Figure 2), retinene enters into the rho- 

 dopsin synthesis as neo-& retinene, but emerges from it on bleaching as all- 

 trans retinene. The latter must be reisomerized to the neo-?> retinene be- 

 fore it can be used to regenerate rhodopsin. ^^^ As an alternate pathway, 

 aW-frans retinene can be reduced to all-^rans vitamin A, which in turn is 

 isomerized to neo-6 vitamin A; the latter compound is oxidized to neo-6 

 retinene by the alcohol dehydrogenase system, after which it is resynthe- 

 sized to rhodopsin. All-^rans vitamin A may be discharged into the blood 

 stream,^"^ and new supplies of neo-6 vitamin A may then be selected from 

 it.^^^ According to Wald et al.,-^ the iodopsin in the chicken retina has 

 precisely the same carotenoid pattern as does the rhodopsin cycle. 



There is considerable evidence that stereoisomeric changes can be ef- 

 fected within the animal. Thus, it has already been pointed out that, when 



