III. nioniEMICAL SYSTEMS 59 



III. Biochemical Systems 



GEORGE WALD 



The metabolism of vitamin A involves three kinds of problem. First in 

 importance is its general function in the tissues. Since a mammal deprived 

 of vitamin A stops growing and eventually dies, it can be assumed that 

 this vitamin plays some fundamental role in cellular metabolism or struc- 

 ture, a role perhaps particularly associated with epithelial cells, since these 

 appear to undergo the earliest changes in vitamin A deficiency. 



Next there is what may be called the vegetative metabolism of vitamin 

 A — its formation from carotenoid precursors, storage and mobilization, 

 absorption, and transport. 



Finally, there is the specific function of vitamin A in vision. In the 

 totality of vitamin A metabolism this would seem to be of minor impor- 

 tance. Two things must be said about this, however: first, that it is the 

 only activity of vitamin A that is well understood; and second, that what 

 has been learned of the visual processes has begun to provide a guide for 

 pursuing the more general metabolism of vitamin A. 



1 shall begin therefore by reviewing the visual biochemistry of vitamin A, 

 stressing particularly those reactions which find some scope outside the 

 retina. Then I shall trj^ to indicate against this background the lines of a 

 general approach to vitamin A metabolism. 



A. RHODOPSIN, PORPHYROPSIN, AND lODOPSINi'^- ^ 



The retinas of most vertebrate animals contain two kinds of light re- 

 ceptor: rods, concerned with vision in dim light; and cones, the organs of 

 vision in bright light and color vision. Each contains a light-sensitive pig- 

 ment, rhodopsin or porphyropsin in the rods, iodopsin in the cones. All 

 three substances are carotenoid proteins, proteins bearing carotenoid pros- 

 thetic groups to which they owe their color and sensitivity to light. 



Rhodopsin is a bright-red pigment, found typicall}^ in the rods of marine 

 fishes and land vertebrates. On exposure to light it bleaches over orange 

 intermediates ("transient orange") to a yellow product ("visual yellow"; 

 "indicator yellow"), and eventually to colorlessness ("visual white"). 



Some years ago these changes in appearance were found to correspond 

 with a cycle of chemical changes, formulated originally as follows :- 



'" The biochemistry of visual systems and their distribution among animals have 



been reviewed in detail by G. Wald, Vitamins and Hormones 1, 195 (1943). 

 'b G. Wald, Harvey Lectures 41, 117 (1945-1946). 

 •<= G. Wald, Dociimenta Ophthalmologica 3, 94 (1949). 



2 G. Wald, J. Gen. Physiol. 19, 351, 781 (1935-1936). 



