iv. biochemical systems 133 



3. Effect of Aminopterin on Purine Synthesis in Mice 



Skipper ct alP found that administration of 4-aminopteroylglutamic acid 

 (A-amiuopterin) or 4-amino-N'''-methylpteroylgliitamic acid (A-methop- 

 terin) decreases the incorporation of racHoactive formate into the nucleic 

 acids and purine fractions to one-fifteenth the normal rate. The antagonists 

 were administered for 7 daj^s prior to the injection of formate. 



4. Relation of p-Aminobenzoic Acid to PGA 



The presence of p-aminobenzoic acid in PGA and the similarity in func- 

 tion has fostered the attractive h>T)othesis that the p-aminobenzoic acid 

 functions as a precursor of PGA. There is no doubt that under certain con- 

 ditions this is true. Whether it is always the case remains a disputed point 

 in spite of the large mass of data brought to bear on this subject. 



If the only function of p-aminobenzoic acid is for synthesis of PGA, then 

 the following conditions might be expected: (a) PGA should promote 

 growth in organisms which require p-aminobenzoic acid; (b) PGA should 

 reverse sulfonamide non-competitively in all susceptible organisms; (c) 

 organisms which require PGA should be resistant to sulfonamides. 



There are organisms whose nutritional requirements for p-aminobenzoic 

 acid can be met by PGA; in other cases this is not true. Pteroylglutamic 

 acid counteracts the toxicity of sulfonamide in only a few organisms. How- 

 ever, those organisms which do require PGA are resistant to sulfonamide. 

 In considering the data pertinent to this subject it might be well to divide 

 them into two categories: first, those in which PGA and p-aminobenzoic 

 acid ha\e a common function; second, those in which they are not inter- 

 changeable. 



a. Biochemical Systems Where p-Aminobenzoic Acid Functions via PGA 



1. Sulfanilamide inhibits the synthesis of PGA by both susceptible and 

 resistant strains of E. coli}'^ Levels of suKanilamide (0.005 M) which pro- 

 duce only partial inhibition of growth decrease the PGA synthesis to less 

 than 1 % of the control level. In resistant strains inhibition of PGA synthe- 

 sis is less marked, but no reduction in growth occurs. This effect is not due 

 to a general lowering of cellular activity, as no marked effect on biotin 

 synthesis occurs. 



2. Increasing concentrations of p-aminobenzoic acid increase the produc- 

 tion of PGA by growing cultures of L. arabinosus, the yield being approxi- 

 mately 5 % on a molar basis.-^' 



-* IT. E. Skipper, J. II. Mitchell, Jr., uiul L. h. liemiett, Jr., Cancer Research 10, 510 



(1950). 

 30 A. K. Miller, Proc. Soc. Exptl. Biol. Med. 57, 151 (1944). 

 " H. P. Sarett, J. Biol. Chem. 171, 265 (1947). 



