Utilization and Interconversion of Purine Bases and Ribonucleosides by Salmonella Typhimurium.

Enteric bacteria, such as Escherichia coli, Aerobader aerogenes, and Salmonella typhimurium are not only able to synthesize adenosine 5’-phosphate and guanosine 5’-phosphate de novo, but they can also derive the purine moieties of these nucleotides from each of the purine bases, adenine, hypoxanthine, guanine, and xanthine, as well as from adenosine, inosine, and guanosine (2). Some of the reactions responsible for the utilization of the purine bases are known. Guanine can be condensed with ribosylpyrophosphate 5-phosphate to yield GMP (3, 4) and GMP can be reduced to inosine 5’-phosphate (5), which is in turn a precursor of AMP (6) (Fig. 1). There seems to be no route from guanine to AMP in which GMP is not an intermediate since mutants lacking GMP reductase cannot obtain the adenine moiety of their nucleic acid from exogenous guanine (7). Xanthine can be converted to xanthosine 5’-phosphate by another pyrophosphorylase (8); this nucleotide is a precursor of GMP which (9), as has just been mentioned, can in turn be converted to AMP. No other pathway for the conversion of xanthine to GMP or AMP appears to exist: xanthosine is not utilized (10) and mutants unable to aminate xanthosine-5’-P can convert xanthine neither to GMP nor to AMP (11). Hypoxanthine is converted to IMP by the enzyme which also catalyzes the conversion of guanine to GMP (3, 4). IMP is converted to AMP via adenylosuccinate (6) and to GMP via xanthosine 5’phosphate by enzymes whose essentiality for the formation of AMP and GMP has also been demonstrated by studies with mutants (2, 12). It is known that adenine can react with PP-ribose-P to produce AMP; this reaction is catalyzed by a pyrophosphorylase distinct from that catalyzing the reactions of hypoxanthine and guanine with PP-ribose-P (13). AMP can be converted to GMP via IMP by a series of enzymatic steps which play a catalytic role in the synthesis of histidine and which involve the replacement of carbon 2 of AMP by a single carbon fragment (7, 14). This pathway normally accounts for approximately one-half of the GMP produced from exogenous adenine; the other half is produced by a pathway in which the purine ring remains intact (7). Histidine inhibits a step in the conversion pathway which is essential for its synthesis (14) (Fig. 1); consequently, in histidine-supplemented media the conversion of adenine to GMP proceeds entirely by the pathway in which the purine ring remains intact (7). The present study was undertaken in an attempt to elucidate