192 PTEROYLGLUTAMIC ACID 



PGA subcutaneously per day or 25 mg. of ascorbic acid orally or a combina- 

 tion of the two was equally effective in reducing the excretion of hydroxy- 

 phenyl derivatives. Only ascorbic acid prevented weight loss and increased 

 serum ascorbic acid. Pteroyltriglutamic acid was effective, but the cor- 

 responding diglutamate was ineffective in reducing the excretion of hy- 

 droxyphenyl compounds in two animals on each compound tested. Ad- 

 ministration of 5 U.S. P. units of anti-pernicious anemia liver extracts 

 (approximately 5 7 of vitamin B12) was without effect. 



The response of scorbutic monkeys to a test load of tyrosine is similar to 

 that of the guinea pig. Salmon and May^^ found that PGA was ineffective 

 in reducing the excretion of hydroxyphenyl compounds even in doses as 

 high as 95 mg. (40 mg. per kilogram of body weight), half being given orally 

 and the other half subcutaneously. Subsequently, these same investiga- 

 tors^^ found that 1.2 mg. of fohnic acid (citrovorum factor) daily given intra- 

 muscularly was ineffective. Ten milUgrams of cortisone, however, injected 

 intramuscularly for 10 days prevented the excretion of large amounts of 

 hydroxyphenyl compounds. 



An effect of PGA in clinical hydroxyphenyluria of infantile scurvy after 

 tyrosine ingestion has been observed in approximately half the cases studied 

 by Govan and Gordon. ^^ In some cases 5 mg. per day produced an effect. 

 In another case 10 mg. per day orally was ineffective but 30 mg. intramus- 

 cularly produced a striking reduction of hydroxyphenyluria. Other cases, 

 in which 10 to 30 mg. intramuscularly was ineffective, promptly responded 

 to the administration of ascorbic acid. 



Morris et al.^°° also observed hydroxyphenyluria in infants \\ith scurvy 

 after tyrosine ingestion. Injection of 45 mg. of PGA to one patient was inef- 

 fective in abohshing the abnormal excretion, but 45 mg. twice daily for 

 several days (corresponding to 13.7 mg. per kilogram per day) did decrease 

 the hydroxyphenyluria. A single dose of 30 7 of vitamin B12 was ineffective, 

 a finding which is parallel to the ineffectiveness of parenteral liver extract 

 in the scorbutic guinea pig. 



Woodruff^ ''^ reported on four cases of tyrosine-induced hydroxyphenyluria 

 in scorbutic infants which were given PGA intramuscularly in doses of 2 

 mg. per kilogram of body weight without any effect on tyrosine metabolism. 

 Apparently the amounts of PGA necessary to reduce hydroxyphenyluria 

 are very large compared to those for growth of the guinea pig and hemato- 

 logical response in scorbutic infants. In the guinea pig 20 mg. per kilogram 



" R. J. Salmon and C. D. May, /. Lab. Clin. Med. 36, 591 (1950). 



98 R, J. Salmon and C. D. May, Arch. Biochem. 32, 220 (1951). 



" C. D. Govan, Jr., and H. H. Gordon, Science 109, 332 (1949). 

 100 J. E. Morris, E. R. Harpur, and A. Goldbloom, J. Clin. Invest. 29, 325 (1950). 

 '<" C. W. Woodnifi", ./. Lab. Clin. Med. 36, 640 (1950). 



