204 THE BIOCHEMISTRY OF B VITAMINS 



Other Catalytic Functions of Folic Acid. The catabolism of tyrosine 

 is altered in folic acid deficiencies produced in animals, 304 in scorbutic 

 guinea pigs, 305 and in humans afflicted with pernicious anemia. 306 This 

 metabolic derangement in the clinical anemias is so consistently observed 

 that it has been suggested as a test having diagnostic value (p. 416) . In 

 these three instances the normal oxidation of tyrosine is blocked, causing 

 the accumulation of phenolic keto acids (probably mono- and dihydroxy- 

 phenylpyruvic acids). The oral administration of either ascorbic acid, 

 folic acid, or liver corrects the defective tyrosine metabolism in the 

 scorbutic guinea pigs 307 ; treating the pernicious anemia patients with 

 liver extracts (containing vitamin Bi 2 , but no folic acid) caused a drop 

 in the concentration of phenolic substances in the blood and urine 308 ; 

 and addition of folic acid in vitro to liver slices from folic acid-deficient 

 rats markedly increased their ability to oxidize tyrosine. 309 These results 

 are of considerable interest, inasmuch as both folic acid and ascorbic 

 acid have been demonstrated to have some metabolic relationship to 

 vitamins Bi 2 , both in the nutrition of microorganisms (p. 206) and in 

 the treatment of pernicious anemia in humans (p. 416) ; however, 

 the interrelationship in terms of cellular reactions is obscure. It may be 

 that folic acid is a component of the tyrosine oxidase system and has 

 functions entirely independent of its role in the metabolism of formic 

 acid derivatives; or, since only intact tissues have been used, the func- 

 tion demonstrated for this vitamin in tyrosine oxidation may be an 

 indirect one. The amounts of folic acid required for correcting the faulty 

 tyrosine metabolism either in vivo or in vitro are of higher order of magni- 

 tude than are those required for alleviating other symptoms of folic acid 

 deficiencies. 



Folic acid has been reported to increase the choline esterase content 

 of blood. 310 The concentration of this enzyme, which catalyzes the hy- 

 drolysis of acetylcholine following its release by neural activity, appar- 

 ently rises when folic acid is administered to experimental animals or 

 even when folic acid is added to samples of blood serum in vitro. In an 

 independent investigation, no evidence was obtained which would sup- 

 port the original claims of folic acid activity. 311 How direct an action 

 folic acid may have upon choline esterase is not known, but in view of 

 its other functions it seems unlikely that folic acid would be directly 

 involved as a coenzyme in this hydrolytic enzyme. 



Dopa decarboxylase (extract of rat kidney) has been postulated to 

 have a coenzyme related to folic acid since pterin analogues inhibit the 

 activity of the enzyme, and the inhibition can be prevented by folic 

 acid. 312 A pyridoxal analogue, which inhibits tyrosine decarboxylase, 

 was inactive. The pyridoxal-like activity of folic acid in this particular 



