title: Effect of 4-azaleucine upon leucine metabolism in Salmonella typhimurium.
abstract: dl-4-Azaleucine (5 x 3(-3)m) added to exponentially growing cells of Salmonella typhimurium resulted in an abrupt cessation of growth lasting 4 to 8 hr followed by a resumption of division. The transitory nature of inhibition was not due to the instability or modification of the analogue or to a derepression of leucine-forming enzymes. Of many compounds tested, leucine served most efficiently to reverse 4-azaleucine-induced inhibition. Inhibition of growth can be explained by the fact that 4-azaleucine inhibits alpha-isopropylmalate synthase, the first enzyme unique to leucine biosynthesis. The analogue was a poor inhibitor of both the transamination of alpha-ketoisocaproate to leucine and the charging of leucine to transfer ribonucleic acid. With a leucine auxotroph starved for leucine, the analogue was incorporated into protein specifically in place of leucine. Such incorporation was accompanied by the death of almost all of the cells.
mesh_terms: D000596:Amino Acids / Q000494:pharmacology*; D000604:Amino Acyl-tRNA Synthetases / Q000378:metabolism; D001426:Bacterial Proteins / Q000096:biosynthesis; D001431:Bacteriological Techniques; D002247:Carbon Isotopes; D002455:Cell Division; D002474:Cell-Free System; D002845:Chromatography; D003124:Colorimetry; D003470:Culture Media; D003998:Dicarboxylic Acids; D005782:Gels; D007930:Leucine / Q000378:metabolism* / Q000031:analogs & derivatives; D007931:Leucyl Aminopeptidase / Q000378:metabolism; D008190:Lyases / Q000037:antagonists & inhibitors / Q000378:metabolism; D008239:Lysine / Q000378:metabolism; D008744:Methylamines / Q000494:pharmacology; D010088:Oxidoreductases / Q000378:metabolism; D011422:Propionates / Q000494:pharmacology; D012475:Salmonella / Q000254:growth & development; D012486:Salmonella typhimurium / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism*; D012822:Silicon Dioxide
chemical_list: D000596:Amino Acids; D001426:Bacterial Proteins; D002247:Carbon Isotopes; D003470:Culture Media; D003998:Dicarboxylic Acids; D005782:Gels; D008744:Methylamines; D011422:Propionates; C000111:azaleucine; D012822:Silicon Dioxide; D010088:Oxidoreductases; D007931:Leucyl Aminopeptidase; D008190:Lyases; D000604:Amino Acyl-tRNA Synthetases; D007930:Leucine; D008239:Lysine