70 VITAMINS A AND CAROTENES 



Alcohol + DPN+ = Aldehyde + DPN-H + H+ 



_ (Aldehyde)(DPN-H)(H+) 

 ^ ~ (Alcohol)(DPN+) 



The new equilibrium constant, A'h, is independent of pH, and for the 

 ethanol-acetaldehyde equilibrium it has the value 1.15 X 10~".^^ 



The outcome of this discussion is that, the higher the alkalinity, the more 

 the alcohol-aldehyde eciuilibrium is displaced in the oxidative direction, 

 toward aldehyde. For an equilibrium condition in which DPN is half re- 

 duced, the ratio of ethyl alcohol to acetaldehyde at pH 7 is about 8000:1, 

 at pH 8 it is about 800: 1, at pH 9 about 80: 1. This may be an important 

 consideration in certain physiological conditions. 



Bliss'*^ has examined the equilibrium between vitamin A and retinene, 

 catalyzed by horse liver alcohol dehydrogenase (Fig. 17). The equilibrium 

 constant, K, depends upon pH just as described above; and again a Ky^ 

 can be computed which is independent of pH. Bliss found K^ in this system 

 to have the value 3.3 X 10~^. That is, this equilibrium lies much further 

 over toward oxidation — tow^ard retinene — than does the alcohol-acetalde- 

 hyde equilibrium. In this case, when DPN is half reduced, the ratio of 

 vitamin A to retinene at pH 6 is about 300: 1, at pH 7 about 30: 1, and at 

 pH 8 about 3:1. 



Another consideration may incline this equilibrium toward retinene. 

 Tbeorell and Bonnichsen^- have observed that alcohol dehydrogenase forms 

 a Complex with cozymase which has a considerably higher oxidation-reduc- 

 tion potential than the free coenzyme. In the presence of high concentrations 

 of the enzyme protein, favoring formation of the complex, a stronger oxida- 

 tion of alcohol to aldehyde is anticipated than is described by the above 

 equations. Theorell and Bonnichsen believe that in liver the molar con- 

 centration of the enzyme protein approaches that of DPN, ensuring nearly 

 complete binding of the coenzyme at neutrality. It is possible that a similar 

 condition exists in the retina. 



All these factors together make it appear that, although the vitamin A- 

 retinene equilibrium catalyzed by animal alcohol dehydrogenase favors 

 reduction, the disproportion between retinene and vitamin A is not extreme, 

 and it would require little in the way of special conditions to displace the 

 equilibrium in the other direction, toward oxidation. This consideration is 

 of great importance in visual systems; and it may prove to play an im- 

 portant part also in other phases of vitamin A metabolism. 



In view of what has been said it may not be clear why in the isolated 

 retina retinene is reduced so completely to vitamin A that finally no retinene 



"1 A. F. Bliss, Arch. Biochem. and Biophys. 31, 197 (1951). 



"2 H. Theorell and R. Bonnichsen, Acta Chem. Scand. 5, 329 (1951). 



