142 PTEROYLGLUTAMIC ACID 



which prevented kidney hemorrhage. Protection against lipotropism could 

 not be obtained by vitamin B12 or PGA alone but was achieved with a com- 

 bination of B12 and PGA or with a higher level of choline. 



The influence of PGA on utilization of methanol as a source of methyl 

 groups in choline has been demonstrated by Verly et al.^^ C^^-Deuterio- 

 methanol was injected into rats deficient in PGA and into similar rats 

 treated with PGA prior to methanol administration. PGA caused a two- 

 to threefold increase in utilization of methanol as measured by the C^^ and 

 deuterium content of isolated choline. Vitamin B12 under similar conditions 

 was without effect. 



/. In Vitro Studies on Methionine Formation 



Livers from PGA-deficient chicks exhibit reduced ability to form methi- 

 onine from homocystine in the presence of choline or betaine (Dinning et 

 al}~). Choline oxidase is also decreased by PGA deficiency as evidenced by 

 slower oxidation of choline. In vitro addition of PGA to the deficient liver 

 does not affect methionine synthesis but addition of PGA to repleted hvers 

 does. This effect of added PGA in vitro is difficult to understand. The effect 

 of PGA on choline oxidase offers an explanation for the effect of this vita- 

 min on methionine synthesis as it has been suggested that choline is first 

 oxidized to betaine before transmethylation can occur. 



V. Specificity of Action 



E. L. R. STOKSTAD 



A large number of PGA analogs have been made. Most of these behave 

 as antagonists and will be considered in another section of this chapter. 

 Certain modifications can be made in the molecule without nullifying the 

 biological activity, but they may modify the activity for different species. 

 This information, which can best be presented in tabular form, is shown in 

 Table IV. 



It is apparent from these data that the higher animals, with the exception 

 of the fox, are capable of utilizing derivatives of PGA containing more than 

 one glutamic acid molecule. It is of special interest that the diglutamic acid 

 derivative containing an a linkage is utilized efficiently by the chick even 

 though it has low biological activity" for L. casei and S. faccalis. Chicken 

 liver conjugase has been shown to split a-glutamic acid linkages more slowly 



" W. G. Verly, J. E. Wilson, J. M. Kinne3^, and J. R. Rachele, Federation Proc. 10, 

 264 (1951). 



