III. BIOCHEMICAL SYSTEMS Kl 



If it wore not for the discrepancy with theory, there would he no reason to 

 doubt, that all fi\e substances are vis-trans isomers of one another. As it is, 

 we believe all of tlieni probably to be ris-trans isomers; yet we siiall defer 

 coming to a final conclusion until further studies have l)een completed.^ 



We have shown that the immediate i)recursor of rhodopsin is the cis 

 isomer of retinene called ncoretinene b. Which isomer of retinene emerges 

 when rhodopsin is bleached? If it were neoretinene b, rhodopsin would 

 bleach reversibly; yet it has been clear since the early experiments of 

 Kiihne that theiv is little regeneration of rhodopsin from the products of 

 its bleaching. 



Rhodopsin 



y \ t,ght 



Neoreilnene b -h opsin ^=^ All-irans roiinene+ opsin 



(o/coho/ dehydrogenase, cozymase) 



NeO'^HaminAh ' ^ A!t-^rons viiaminA 



Fig. 25. Geometrical isomers of retinene and vitamin A in the rhodopsin cj-cle. 

 Retinene enters the synthesis of rhodopsin as neoretinene b and emerges from its 

 bleaching all-//a«s. This must be isomerized to neoretinene b before it can regenerate 

 rhodopsin. Alternatively it is reduced to all-/mAts vitamin A, which must be isom- 

 erized to, or e.xchanged for, neovitamin \b before it can engage again in rhodopsin 

 synthesis. Some isomerization occurs in the eye tissues, but much of the cycle involves 

 also the discard of all-//rt«s vitamin A into the blood circulation, and the selection 

 from it of new supplies of neovitamin Ab. (From R. Hubbard and G. Wald."") 



The retinene formed when rhodopsin bleaches is in fact the inactive, 

 all-//-ans isomer. That is, retinene enters rhodopsin as one isomer, and 

 emerges as another. This must be isomerized to neoretinene b before it can 

 re-enter the synthesis of rhodopsin. A cycle of stereoisomerization of reti- 

 nene, or of the corresponding vitamin A, is therefore an intrinsic component 

 of the rhodopsin system.^'' ^^'^ 



The system may now be formulated as in Fig. 25. The bleaching of 

 rhodopsin yields aW-trans retinene. In the retina this can be isomerized in 

 part by light, in part apparently also by enzymes present in the eye tissues, 

 to neoretinene b, which reverts to rhodopsin. Some retinene, before it has 

 isomerized, is reduced by the alcohol dehydrogenase system to all-/rans 

 vitamin A. This in turn must be isomerized to neovitamin Ab before it 

 can re-enter the rhodopsin system. Not all of this need occur in the eye 

 itself. There is good evidence that during a long exposure of the eye to 



