GEORdE WALD 727 



the alcohol dehydrogenase system in the oxidative direction, speeding 

 the formation ol retinene, and hence of rhodopsin. 



Exactly similar arrangements exist for all the other vertebrate sys- 

 tems. Each of tiie visual j)igments bleaches over corresponding lumi- 

 and meta-jiigments; and the alcohol dehydrogenase system and its 

 coupling ^vith photopigment synthesis present similar relationships 

 in all vertebrate retinas. 



Cis-trans Isotnerism 



To synthesize a visual pigment a specific configuration of vitamin 

 A or retinene is needed. Vitamin A or Ao possesses four double bonds 

 in its side-chain. These can occur in either trans or cis configuration, 

 yielding an array of geometrical isomers (Fig. 2) . 



The most stable and prevalent form of these molecules, the all- 

 trans configuration, is not active in the synthesis of visual pigments. 

 For this process, some cis configuration is needed (28) . 



We owe much of our knowledge of cis-trans isomerism in carotenoids 

 to the penetrating studies of Zechmeister (55-57) and the associated 

 theoretical exposition of Pauling (33, 57, 34) . Pauling had pointed 

 out that in such an isoprenoid structure as here considered one 

 should expect to find the cis configuration only in those double bonds 

 adjacent to methyl groups, here numbered 9 and 13. At either of the 

 other positions — 7 or 1 1 — the attempt to go from the trans to the 

 cis configuration would encounter internal steric hindrance ("molecu- 

 lar overcrowding") : a cis linkage at double bond 7 would bring the 

 methyl groups on carbons 1 and 9 into conflict; and at double bond 

 11, the hydrogen atom on carbon 10 would overlap with the methyl 

 group on carbon 1 3 (Fig. 2) . A cis linkage always introduces a bend 

 in the chain; but at such a hindered cis linkage one should have 

 not only a bend but a twist. The molecule could not lie flat — it could 

 not be co-planar — and since this condition must be approximately ful- 

 filled for resonance to occur, and resonance is one of the primary 

 conditions of stability, one should expect that a molecule containing 

 such a hindered cis linkage would be unstable, and hence would not 

 be found in appreciable quantity. It was expected, therefore, that 

 in such a molecule as vitamin A one would find only the four 

 relatively unhindered geometric isomers: all-trans, 9-cis, \5-cis, and 

 9, \3-dicis (Fig. 2). 



Reasonable as this seemed, it has now become clear that all known 

 visual pigments that have been analyzed contain as chromophore the 

 sterically hindered 1 l-cis isomer of retinenej or retineneo, named 



