472 R. E. HANDSCHUMACHER AND A. D. WELCH 



idine nucleotides. As described in detail in Chapters 35 and 36, each of 

 several steps in the biosynthesis of purine- and pyrimidine-containing com- 

 pounds requires glutamine as the amino-donor. These steps are: (a) the 

 animation of l-pyrophosphoryl-ribose-5-phosphate (PRPP) to form 1- 

 amino-ribose-5-phosphate (ribosylamine-5-phosphate) 110 * 1U (6) the conver- 

 sion of formylglycinamide ribonucleotide to the corresponding formamidino 

 derivative, 112 (c) the conversion of xanthine ribonucleotide to guanylic 

 acid, 113, m and (d) the formation of a ribonucleotide of cytosine from the 

 corresponding derivative of uracil. 115-117 The introduction of these ring-ni- 

 trogen atoms and amino groups into the purines and pyrimidines is to be 

 distinguished from the incorporation of nitrogen into position 1 of the py- 

 rimidine rings, which is mediated by carbamylphosphate, or into position 1 

 of the purine ring and position 3 of the pyrimidines, for which aspartic acid 

 is the donor. 



Although it might be the fond conviction of the theoretical chemist and 

 biologist that the rational design of structures capable of interfering with 

 nucleic acid metabolism will obviate the need for random screening of com- 

 pounds, that time has not yet arrived. Thus, it was through routine testing 

 of fermentation "beers" for antimicrobial and carcinostatic activity that 

 the antibiotics azaserine [O-diazoacetyl-L-serine; (VII)] 118123 and DON [6- 

 diazo-5-oxo-L-norleucine ; (VIII)] 124 " 126 were discovered (see also Chapter 35). 



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