84 VITAMINS A AND CAROTENES 



Possibly the high selectivity in carotenoid absorption exhibited by some 

 animals and the catholicity by others may have its source in the existence 

 in the blood plasma of more or less specific proteins, which permit the 

 absorption of those carotenoids with which they can combine, and exclude 

 all others from entering the system. 



In any case, one can be sure that carotenoids are regularly brought into 

 water solution in the blood by binding to protein. We have shown also that 

 retinene is brought into solution in tissue extracts by a similar process,^^ 

 and Ames and Harris^" have demonstrated the solubilization of vitamin E 

 by proteins. This appears to be a very general process for carrying fat-soluble 

 substances into water solution in the body fluids and tissues. ^^ It may 

 represent the active or "mobilized" form of the carotenoids, as opposed to 

 simple solution in fat globules, the form in which they are stored. It would 

 then be in combination with proteins that carotenoids are made accessible 

 to enzymes; and on occasion the enzyme protein itself would bind them. 



This is not even now an empty hypothesis. Retinene has been shown to 

 combine spontaneously with a variety of proteins,^' and we have direct 

 evidence of its combination in the retina and in tissue extracts with alcohol 

 dehydrogenase and with opsin.^^ Vitamin A also, since it is acted upon by 

 alcohol dehydrogenase, must combine Avith this enzyme. 



Another process needs to be considered which has been referred to above 

 only in passing. This is the esterification of vitamin A. The vitamin A of 

 the blood plasma is predominantly the free alcohol, whereas that of the 

 liver is overwhelmingly esterified.^^ Glover et al}^ found evidence of an 

 active esterification of vitamin A in the intestinal wall and in subcutaneous 

 tissues. It can be added that vitamin A seems to be esterified rapidly in the 

 eye tissues. We have found in partition experiments with extracts from 

 frog and cattle eyes that the vitamin A of both the retina and the pigment 

 epithelium is predominantly in the ester form. 



All these processes taken together compose the following view of vitamin 

 A metabolism. i3-Carotene, perhaps in a water-soluble complex with protein, 

 is oxidized by carotene oxidase to retinene. This is reduced by the alcohol 

 dehydrogenase system to vitamin A. Some of the vitamin A is converted 

 in the tissues to esters, which are in turn hydrolyzed to the free alcohol for 

 transport and to perform certain metabolic functions. 



The curious thing about this view of events is that it brings the general 

 metabolism of vitamin A into such close relation with the visual processes. 

 In both cases a carotenoid protein is degraded over retinene to vitamin A, 



«» S. R. Ames and P. L. Harris, Intern. Rev. Vitamin Research 22, 26 (1950). 

 61 B. D. Davis, Am. Scientist 34, 611 (1946). 



«2 S. Bali, F. D. Collins, R. A. Morton, and A. L. Stubbs, Nature 161, 424 (1948). 

 63 E. LeB. Gray, K. C. D. Hickman, and E. F. Brown, J. Nutrition 19, 39 (1940); 

 H. M. Kascher and J. G. Baxter, Ind. Emj. Chem. Anal. Ed. 17, 499 (1945). 



