Nucleosides and Nucleotides in the Presence of Growth Inhibitors

The action on bacteria of sulfonamides and structural analogs of purines and pyrimidines has been the subject of many publications. In the course of these studies, a number of nucleosides and nucleotides have been isolated which, in certain cases, have provided valuable information about purine and pyrimidine biosynthesis. 

5-Amino-4-imidazolecarboxamide was isolated from sulfonamide-inhibited cultures of Escherichia coli. - ° This substance also accumulates when Escherichia coli are inhibited by aminopterin, and is found in the culture medium of a purine-requiring mutant of Escherichia coZf. ° 

5-Amino-N-D-ribofuranosyl-4-imidazolecarboxamide (XXII) has been detected and isolated by several workers. It was isolated, as crystal- 

Small quantities of the 5-amino-4-imidazolecarboxamide nucleotide were also isolated from the culture medium of Escherichia coli grown under sulfonamide bacteriostasis.i i This substance is considered to be an intermediate in purine biosynthesis, both in micro-organisms and in mammalian cells. In sulfonamide-inhibited cells and in the purine-requiring mutant of Escherichia coli, there is a block in the conversion of 5-amino-4-imidazole-carboxamide n-ribonucleotide to inosinic acid. The accumulated nucleotide in the bacterial cell is probably attacked by phosphatases this would explain why the nucleoside is the main metabolite. 

It has been shown that the accumulation of 5-amino-iV-D-ribosyl-4-imidazolecarboxamide in a purine-requiring mutant of Escherichia coli ceases when the bacteria are supplied with an excess of purine. The site of inhibition is, apparently, before the formation of the imidazole ring occurs, but after the formation of the D-ribosyl moiety, since adenine has only a 

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