The Effect of Sulfonamides on Respiratory Enzymes

In recent years it has been established that sulfonamides inhibit the respiration of certain bacteria, yeasts, and tissues. This inhibition was first observed on intact bacteria by Barron and Jacobs (l), and it seems to occur simultaneously with the cessation of growth in the presence of the sulfonamide (2). On the basis of numerous investigations, it can be assumed that certain relationships exist between sulfonamide inhibition of growth and of respiration. Sulfonamides may affect these processes by interfering with the synthesis of the coenzymes necessary for respiration (3). However, it seems probable that the effect of sulfonamides on bacterial respiration is only indirectly linked to their effect on growth (4-7). The inhibitory effect of sulfonamides on respiration has not yet been completely explained, although a number of studies point in the direction in which further progress may be made. It has been shown that sulfonamides form dissociating complexes with enzymes and other proteins (8-15) and in several such cases loss of enzyme activity was found to result (16-21). The work of Dorfman, Rice, Koser, and Saunders (22) and Berkman and Koser (23) indicates that phosphopyridine nucleotides participate also in bacterial respiration and it explains the restoration of normal bacterial growth upon addition of pyridine nucleotides to the culture medium, in the presence of sulfonamides (24). It has also been reported that sulfonamides inhibit the respiration of Plasmodium hmowled in the presence of glucose (25), which may be indicative of interference with oxidation of carbohydrates. In order to establish the point at which the drug interferes with respiration, it seemed of interest to investigate the effect of sulfonamides on each of the isolated components of the respiratory enzyme system involved in the oxidation of glucose-6-phosphate. The tests applied here for the components of this system possess a high degree of specificity which permits conclusive evaluation of drug action. The results thus obtained may contribute to a more precise understanding of the inhibition caused by sulfonamides. E$ect of Sulfonamides on Cytochrome Oa’dae-Cytochrome oxidase was