III. BIOCHEMICAL SYSTEMS 67 



I).jvpaitMl by oxitliziiig (he corrivspondiiig vitamin A on manganese dioxide. 

 Wlien these tlu'ee components are mixed, the retinene is reduced almost 

 completely to vitamin A (Fig. 16). 



An enzyme called alcohol dehydrogenase has long been known to occm- 

 in a ^'ariety of animal tissues — liver, kidney, and intestine. This, with 

 cozymase as coenzyme, catalj^zes the eciiiilibria between various alcohols 

 and their aldehydes.^' Shortly after the retinene reductase system was 

 found in the retina, Bliss'- reported that crude preparations of liver alcohol 

 dehydrogenase catalyze the equilibrium between retinene and vitamin A. 

 We have confirmed this observation, using crj'stalline alcohol dehydrogenase 

 from horse li\'er.'' Conversely it was shown that the enzyme present in 

 frog retinas oxidizes ethyl alcohol to acetaldehyde (W. Yudkin, unpublished 

 observations). 



There is no present reason, therefore, to distinguish the retinal enzyme 

 from the alcohol dehydrogenase found in other animal tissues. We shall 

 refer to it hereafter by this more general designation. 



Cozymase introduces a second vitamin into the chemistry of visual 

 systems. Its active constituent is nicotinamide, the antipellagra factor of 

 the vitamin B complex. In the retina it performs the peculiar function of 

 helping to regenerate the vitamins A. 



In the system as assembled in vitro there is further room for the action 

 of vitamins. Retinal homogenates and extracts contain an enzyme which 

 destroys cozymase, a so-called nucleosidase, which is widely distributed in 

 animal tissues. Cozymase is protected from this attack by the presence of 

 free nicotinamide;''* or alternatively by a-tocopheryl phosphate.'^ When 

 the latter is used in the present system, three vitamins cooperate in a single 

 reaction in solution — ^vitamin E phosphate protects the nicotinamide com- 

 plex, DPN, as it reduces retinene to vitamin A. 



Alcohol dehydrogenase is the only enzyme system known to act directly 

 upon vitamin A. It opens a broad series of relationships between the visual 

 processes and other aspects of metabolism. In alcohol dehydrogenase a 

 wide variety of tissues share an enzyme which permits them to negotiate 

 reversible transformations between vitamin A and retinene; and through 

 cozymase these processes are connected with the main pathways of cellular 

 respiration and fermentation, in which this coenzyme plays a central role. 

 Quite apart from the visual processes, the alcohol dehydrogenase system 



" C. Lutwak-Mann, Biochem. J. 32, 1364 (1938). 



32 A. F. Bliss, Biol. Bull. 97, 221 (1949). 



33 R. Hubbard and G. Wald, Proc. Natl. Acad. Set. U.S. 37, 69 (1951). 



3^ P. J. G. Mann and J. H. Quastel, Biochem. J. 35, 502 (1941) ; P. Handler and J. R. 



Klein, J. Biol. Chcm. 143, 49 (1942). 

 35 M. E. Spaulding and W. D. Graham, J. Biol. Chcm. 170, 711 (1947). 



