the al\-trans isomer, originally prepared by Ball et al. 

 (3); the three unhindered cis isomers — neo-a (i3-«.s-), 

 iso-a (g-m) and iso-A ((),\j,-dicis); and a hindered 

 cis isomer of the type which had been deemed im- 

 probable on theoretical grounds (fig. 5). This hin- 

 dered cis isomer, neo-A (ii-m), is the precursor of 

 rhodopsin (32, 39).^ 



The synthesis of rhodopsin proceeds in two stages. 

 First, vitamin A is o.xidized to retinene; then rctinene 

 couples with opsin. The first process is relatively 

 indiflferent to isomeric configuration. It is the coupling 

 of retinene with opsin that is isomer-spccific. 



On incubation with opsin in the dark, neo-6 

 retinene yields rhodopsin, indistinguishable from 

 that extracted from the dark-adapted retina. On 

 similar treatment, iso-a retinene yields a very similar, 

 light-sensitive pigment, with its X„,,,s displaced about 

 13 m/i toward shorter wavelengths. This is called 

 iso-rhodopsin. The remaining isomers are inacti\e 

 (fig. 6). 



When rhodopsin is bleached, the retinene which 

 emerges is a\\-trans. This must be isomerized to the 

 active isomer, neo-6, before it can resynthesize 

 rhodopsin. A cycle of cis-trans isomerization is there- 

 fore an intrinsic part of the rhodopsin system. 



A single passage through this cycle is shown in 

 figure 7. On the left, a mixture of neo-A retinene and 

 cattle opsin in aqueous solution incubated in the 

 dark forms rhodopsin. On the right, the rhodopsin 

 formed in this way is bleached to a mixture of all- 

 Irans retinene and opsin. The extinction of retinene 

 which emerges on the right is much higher than that 

 which enters on the left. That is because the specific 

 extinction of a\\-trans retinene is higher than that of 

 the neo-i isomer. 



The mechanism by which the eve converts all- 

 trans retinene, which results from bleaching rho- 

 dopsin, to nco-h retinene is not entirely clear. All- 

 trans retinene is isomerized to a mixture of cis and 

 tram isomers by simple exposure to light. This is a 

 second photochemical process in the rhodopsin 

 system. The eye tissues also contain an enzyme, 

 retinene isomerase, which catalyzes specifically the 

 interconversion of a\\-trans and neo-6 retinene, and 

 which is also light-sensitive (31). There probably are 

 additional mechanisms for converting aW-trans rcti- 

 nene or vitamin A to the neo-A isomer. 



The rhodopsin system can therefore be formulated 



^A si.xth isomer of retinene, called neo-c (11, lydicis"), 

 has since been synthesized by Oroshnik (39). 



THE PHOTORECEPTOR PROCESS IN VISION 675 



as follows (34) : 



Rhodopsin 



Neo-6 retinene -t- opsin - 



-. W\-lrans retinene -|- opsin 



[ (alcohol dehydrogenase, DPN) 



J 



Neo-A vitamin A - 



; All-;raHf vitamin A 



Vitamin A emerges from the bleaching of rhodopsin 

 as the free alcohol; yet the great bulk of the vitamin 



H,C C 



^^'\./ 



C-CH3 



CH. 



CHf 



-% 



^c'"" 



.'T.'^'^^'H 



CH 



CHg^OH 



11 -cis (neo-b) 



FIG. 5. The sterically hindered neo-b (11 -aV) isomer of 

 vitamin A, precursor of rhodopsin and iodopsin. [From Orosh- 

 nik e/ al. (40).] 



0.3 __ 



O.Z. 



0.1 



0._ 



-0./-_ 



"1 1 1 \ 



opstn -f- retinene isomers 



o a!I~iran5 

 • neoretinene a 

 9 neoretinGne b 

 e isoreiinene a 



— o 



C 



wave length — m/^ 



400 



450 500 



550 



600 



FIG. 6. The products of incubating various geometrical 

 isomers of retinene with cattle opsin. Difference spectra are 

 shown — differences in the absorption spectra before and after 

 bleaching in the presence of hydroxylamine. A\l-lrans and 

 neo-a retinene yield no light-sensitive pigment. Neo-A retinene 

 yields rhodopsin; iso-a retinene, iso-rhodopsin. Iso-A retinene, 

 though itself inactive, isomerizes preferentially to iso-a which 

 yields iso-rhodopsin. [From Hubbard & Wald (34).] 



