374 ASCORBIC ACID 



No abnormalities except occasional small hemorrhages have been found 

 in the adrenal glands of human beings with scurvy even though there 

 appears to be some relationship between ascorbic acid and adrenal func- 

 tion. ^''*^ Such a relationship is suggested by the lowered ascorbic acid level 

 of the adrenal gland under stress or treatment with adrenocorticotropic 

 hormone, the lowered cholesterol of the adrenal gland under these circum- 

 stances, and the decrease in the urinary output of cortical steroids by 

 scorbutic guinea pigs. However, tests of adrenal function in monkeys^^ 

 and human beings^^ with scurvy so far have been normal, and recent es- 

 timations of the output of 17-ketosteroids and formaldehydegenic sub- 

 stances in the urine of scorbutic guinea pigs give no indication of adrenal 

 insufficiency.®^' ®^ 



The connection between the physiologic and biochemical abnormalities 

 which are now known to occur in ascorbic acid-deficient animals and 

 human beings and the pathology observed in these subjects is not clear. 

 As already mentioned, ascorbic acid is necessary for the complete me- 

 tabolism of tyrosine, phenylalanine, and dihydroxyphenylalanine (dopa). 

 Errors in the metabolism of these amino acids and the interference with 

 the metabolism of dihydroxyphenylalanine may account for the excessive 

 pigmentation of the scorbutic patient. These metabolic abnormalities re- 

 sult in a type of alkaptonuria sometimes called ''tyrosyluria." 



The abnormality in folic acid metabolism induced by ascorbic acid 

 deficiency may account for the macrocytic type of scorbutic anemia as 

 it may account for some cases of megaloblastic anemia of infancy. Abnor- 

 malities in the metabolism of mucopolysaccharides, possibly mediated 

 through abnormalities in enzyme systems such as the hyaluronidases, may 

 account for the lesions of bone, blood vessels, and fibrous tissues. 



It is evident from the many morphologic lesions of scurvy and the 

 diverse biochemical reactions known to be affected adversely by a deficiency 

 of ascorbic acid that this vitamin is of very wide physiologic importance. 

 The fact that it is such a strong reducing agent has led to the suggestion 

 that it acts as a regulator of oxidation-reduction potential throughout the 



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62 M. A. Sayers, G. Sayers, and L. A. Woodbury, Endocrinologij 42, 379 (1948). 



63 W. H. Daughaday, H. Jaffe, and R. H. Williams, J. Clin. Endocrinol. 8, 244 (1948). 

 6^ J. C. Beck, M. M. English, J. W. Hackney, and K. R. Mackenzie, J. Clin. Invest. 



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 66 Editorials and Comments: /. Am. Med. Assoc, p. 825 (1951). 

 66 C. T. Stewart, R. J. Salmon, and C. D. May, J. Lab. Clin. Med. 40, 657 (1952). 

 6^ H. S. Treager, G. J. Gabuzda, N. Zamcheck, and C. S. Davidson, Proc. Soc. Exptl. 



Biol. Med. 75, 517 (1950). 



68 B. E. Clayton and F. T. Prunty, Brit. Med. J. II, 927-930 (1951). 



69 E. M. Nadel and J. J. Schneider, Federation Proc. 11, 263 (1952). 



