J. Gots, E. Chu
Oct 1, 1952
Citations
1
Influential Citations
26
Citations
Journal
Journal of Bacteriology
Abstract
The evidence that p-aminobenzoic acid functions in purine synthesis was originally suggested by nutritional studies and by systems involving inhibition analysis as recently reviewed by Shive (1951). The occurrence of 4-amino-5imidazolecarboxamide in sulfonamide inhibited cultures of Escherichia coli offered a lead in localizing the site of p-aminobenzoic acid involvement in purine synthesis (Stetten and Fox, 1945; Shive et at., 1947). It was postulated that p-aminobenzoic acid through its functional derivative was required for the addition of a carbon unit to 4-amino-5-imidazolecarboxamide thus forming the purine ring. That 4-amino-5-imidazolecarboxamide is indeed associated with a deficiency in purine synthesis was demonstrated by its accumulation by a purine requiring mutant of E. coli in the absence of any inhibitor (Gots, 1950a). Further evidence that 4-amino-5-imidazolecarboxamide can function as a purine precursor has been shown by tracer studies in pigeon liver (Schulman, Buchanan, and Miller, 1950) and yeast systems (Williams, 1951). On this basis, using the occurrence of 4-amino-5-imidazolecarboxamide as an index of a deficiency in the ability of an organism to convert it to purines, we have investigated further the role of p-aminobenzoic acid and related substances in this reaction. Attempts to correlate the mechanism of sulfonamide inhibition with this function of p-aminobenzoic acid were unsuccessful (Gots, 1950b) since neither paminobenzoic acid nor its derivatives, folic acid or oitrovorum factor, could function in bringing about utilization of 4-amino-5-imidazolecarboxamide by wild type E. coli after its accumulation or when added exogenously. If the accumulation of 4-aino-5-imidazolecarboxamide in the sulfonamide inhibited systems is indeed due to the action of the drug as an antimetabolite of p-aminobenzoic acid, then other p-aminobenzoic acid antimetabolites should show the same effects. Furthermore, a p-aminobenzoic acid deficient system, as in a p-aminobenzoic acid auxotroph, should bring about similar consequences in the absence of any inhibitor. These results have indeed been obtained and form the subject of this communication. The role and interrelations of other postulated end products of p-aminobenzoic acid activity and related compounds, particularly methionine and vitamin B12, also have been investigated.