Chapter 13 

 PTEROYLGLUTAMIC ACID 



Page 



I. Noiuciiclaturo and Foriimla 89 



II. Chemistry 91 



A. Isolation 91 



1. Of Pteroylglutamic Ac-id (PGA) 91 



2. Of PGA Conjugates 93 



3. Degradation Reactions 95 



B. Physical and Chemical Properties 99 



1. Hj'drogenation 101 



2. Other Reactions 103 



C. Constitution 104 



D. Synthesis 104 



1. Simultaneous Condensation of Triaminopyrimidine, 3-Carbon In- 

 termediate, and Aromatic Amine 106 



2. Condensation of Preformed Pterin with Aromatic Amine. . . . 107 



3. S3^nthesis of Pteroylpolyglutamic Acid DerivativCvS 108 



E. Specificity 109 



1. Chemistry of Rhizopterin (Formyl Pteroic Acid) 109 



2. Chemistry of Citrovorum Factor (Leucovorin, Folinic Acid) . . 110 

 III. Industrial Preparation 121 



IV. Biochemical Sj'stems 124 



A. Coenzymes and Enzymes 124 



1. Function of PGA in Synthesis of Purines and Pyrimidines . . . 124 



2. Sulfonamide, p-Aminobenzoic Acid, and Purine Relationships . . 127 



B. Mechanism of Action 128 



1. Role of 4-Amino-5-Imidazolecarbo.\amide in Purine Synthesis . . 128 



2. Inosinic Transformylase 132 



3. Effect of Aminopterin on Purine Synthesis in Mice 133 



4. Relation of p-Aminobenzoic Acid to PGA 133 



5. Role of PGA in Synthesis of Amino Acids 136 



6. PGA in Single-Carbon Transfer in Animals. ... .... 137 



y. Specificity of Action 142 



A. Relation of Xanthopterin to PGA 145 



B. PGA Antagonists 149 



1. Substituted Pj^imidines 150 



2. Purine Derivatives 151 



3. Pteridine Derivatives 152 



4. Modification of Pterin Nucleus 153 



5. Pteroyl Derivatives of Different Amino Acids 154 



6. Alkyl Derivatives 155 



7. 4-Aminopteroylglutamic Acid Derivatives 157 



8. Effect of Antagonists on Experimental Tumors 159 



VI. Estimation 161 



87 



