156 NITROGEN METABOLISM 



result is not due to direct inhibition of this enzyme [9]. The 

 oxidase activity of whole cells of streptomycin resistant 

 variants of Myc. smegmatis was very much less sensitive and 

 like the mammalian enzyme, only inhibited by high concen- 

 trations [32]. Other experiments indicate that this antibiotic 

 interferes with the entry of pyruvate into a terminal 

 pathway responsible for its oxidation [12, 25], and that this 

 pathway does not involve conversion to acetate and con- 

 densation of acetate with oxaloacetate to form citrate. 

 Streptomycin-resistant strains of Esch. coli do not possess 

 this pathway, and although it is also present in mammalian 

 mitochondria, permeability barriers prevent streptomycin 

 from having any effect [26]. Chloramphenicol inhibits 

 esterases in the cell-free state, but had no effect on forty 

 other enzymes examined [24]. There is some evidence that 

 it interferes with the metabolism of aromatic amino-acids, 

 e.g. with Esch. coli, the addition of phenylalanine, tyrosine 

 or tryptophan overcame the growth inhibitory effects of 

 low concentrations of chloramphenicol [30], and in Esch. 

 coli, as in Salm. typhosa, it appears to prevent the conversion 

 of anthranilic acid to indole [2]. 



Although the above account is very incomplete, it serves 

 to illustrate that much has still to be discovered before a 

 precise statement can be made concerning the mode of 

 action of the sulphonamides and antibiotics. Nevertheless, 

 apart from their potential value in the development of new 

 chemotherapeutic agents, such studies have made and can 

 make valuable contributions to the general pool of bio- 

 chemical knowledge. 



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1. Albert, A. (1951), Selective Toxicity, Methuen, G.B. 



2. Bergmann, E. D. and Sicher, S. (1952), Nature, 170, 931 



3. Davis, B. D. (1951), 3^. Bact., 62, 221 



4. and Mingiolo, E. S. (1950), J. Bad., 60, 17 



5. Gale, E. F. (1947),^. gen. Microbiol, i, 327 



6. and Folkes, J, P. (1953), Biochem. J., 53, 493 



7. and Paine, T. F. (195 1), Biochem. J., 48, 298 



8. and Taylor, E. S. (1947), J. gefi. Microbiol., i, 314 



9. Geronimus, L. H. (195 1), Bad. Proc, 128 



