Mechanism of competitive inhibition of p-aminobenzoic acid oxidation by p-aminosalicylic acid.

The proposed mechanism(s) associated with the inhibition of essential metabolic reactions by various compounds has received a great deal of attention in recent years, since antimetabolites have proved useful in several chemotherapeutic areas and in studying various metabolic reactions. The significance of p-aminobenzoic acid in microbial nutrition was first emphasized when Woods (1940) and Woods and Fildes (1940) reported that this metabolite protected yeast against the growth inhibiting action of sulfanilamide. Youmans, Raleigh, and Youmans (1947) reported that p-aminosalicylic acid inhibited growth of virulent strains of the tubercle bacilli and this antagonism was due to anti-p-aminobenzoic acid activity. More recently, Hedgecock (1958) demonstrated that p-aminobenzoic acid competitively antagonized the inhibitory effect of p-aminosalicylic acid on the growth of Mycobacterium tuberculosis. Nutritional studies have indicated that paminobenzoic acid may fulfill a dual role in microbial metabolism. Durham (1956) reported that p-aminobenzoic acid was capable of serving as an oxidizable substrate for certain microorganisms in addition to functioning as a growth factor. Results obtained from additional investigations indicated that the utilization of p-aminobenzoic acid as a sole source of energy for aerobic growth is also competitively inhibited by paminosalicylic acid (Durham, 1957). Durham and Hubbard (1959) suggested that p-aminosalicylic acid influenced the assimilation of p-aminobenzoic acid by competing with the substrate for the specific transport mechanism(s) in the cell membrane thereby controlling oxida-