IV VITAMIN BIOSYNTHESIS 121 



converted to N^'^-formyl THFA (Greenberg, 1954). Tetrahydrofolic acid activates 

 the interconversion of glycine and serine by pigeon liver under conditions where 

 folic or folinic acids are inactive (Kisliuk and Sakami, 1955). N'^-formyl THFA is 

 30 times as active as folic acid in reversing the toxicity of folic acid antagonists to 

 S. faecalis. A series of polyglutamyl— folic acid derivatives (CoC) are active in 

 catalyzing the conversion of serine to glycine in Clostridium HF (Wright and Stadt- 

 man, 1956; Wright, 1956). Folic acid, N^-formyl folic acid, and Anhydroleucovorum 

 w^ere inactive while folinic and THFA were active only at much higher concentra- 

 tions than was necessary for CoCI. 



v. SUMMARY 



Our discussion began with an outline of the energy yielding metabolic cycles of 

 the cell and the various mechanisms by which the energy generated in biochemical 

 reactions is conserved in compounds such as ATP, which contain "energy- rich 

 bonds''. The many reactions in which ATP and related nucleotides participate 

 were next described. Thirdly, we examined the metabolic pathways which are of 

 significance in connection with the biosynthesis of the major building blocks of 

 protoplasm. It was noted that most of the latter substances are formed from 

 metabolites of the glycolytic sequence and the citric acid cycle or from the amino 

 acids which are closely related to these sequences. Thus, the catabolic cycles of 

 the cell were shown to be of significance not only to generate the energy needed 

 for growth but also as a source of the carbon fragments out of which the essential 

 metabolites are constructed. Likewise, it was shown that ATP and related nucleo- 

 tides are required in various activation reactions and as constituents of coenzymes 

 of numerous transfer reactions, but also as building blocks of the nucleic acids. 

 Finally, the double function of glutamine, glutamic acid, and aspartate as building 

 blocks of proteins and substrates of many nitrogen transfer reactions was indicated. 



Clearly, enormous progress has been made during the last two decades in char- 

 ting the metabolic sequences of the cell, in isolating the intermediates, and in 

 purifying the enzymes of these sequences. We may anticipate that this knowledge 

 will serve as a springboard for further advances in related fields. Certainly, there 

 should be accelerated progress in connection with a) the regulation of intracellular 

 metabolism, b) the control of enzyme synthesis, and c) the terminal mechanisms of 

 macromolecular biosynthesis, and d) the pathways of vitamin synthesis. 



Cells are equipped with remarkably efficient mechanisms for providing for an 

 economical operation and integration of their biosynthetic pathways. The ex- 

 periments of Chance and others have clarified the mechanisms by which the rate 

 of respiration and glycolysis are controlled. As B. D. Davis has emphasized, the 

 mechanisms regulating the synthesis of protoplasmic building blocks are operative 

 against the background of the capacity to carry out various of the biosynthetic 

 reactions at rates far out of proportion to the rest of the metabolism of the cell. 

 Many auxotrophic mutant strains of microorganisms excrete a precursor of a 

 blocked reaction, or sometimes the end product of a diflferent biosynthetic chain, in 

 large amounts. Indeed, in some instances, the amount of the precursor accumulated 

 may even exceed the dry weight of the microorganisms themselves. Yet, the ac- 



Lileriilure fi. 124 



