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. 1971 Oct;108(1):95–104. doi: 10.1128/jb.108.1.95-104.1971

Effect of 4-Azaleucine upon Leucine Metabolism in Salmonella typhimurium1

B Stieglitz a,2, J M Calvo a
PMCID: PMC247037  PMID: 4330744

Abstract

dl-4-Azaleucine (5 × 3−3m) 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 α-isopropylmalate synthase, the first enzyme unique to leucine biosynthesis. The analogue was a poor inhibitor of both the transamination of α-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.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Alexander R. R., Calvo J. M., Freundlich M. Mutants of Salmonella typhimurium with an altered leucyl-transfer ribonucleic acid synthetase. J Bacteriol. 1971 Apr;106(1):213–220. doi: 10.1128/jb.106.1.213-220.1971. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Argoudelis A. D., Herr R. R., Mason D. J., Pyke T. R., Zieserl J. F. New amino acids from Streptomyces. Biochemistry. 1967 Jan;6(1):165–170. doi: 10.1021/bi00853a027. [DOI] [PubMed] [Google Scholar]
  3. BURNS R. O., UMBARGER H. E., GROSS S. R. THE BIOSYNTHESIS OF LEUCINE. III. THE CONVERSION OF ALPHA-HYDROXY-BETA-CARBOXYISOCAPROATE TO ALPHA-KETOISOCAPROATE. Biochemistry. 1963 Sep-Oct;2:1053–1058. doi: 10.1021/bi00905a024. [DOI] [PubMed] [Google Scholar]
  4. Calvo J. M., Bartholomew J. C., Stieglitz B. I. Fluorometric assay of enzymatic reactions involving acetyl Coenzyme A in aldol condensations. Anal Biochem. 1969 Apr 4;28(1):164–181. doi: 10.1016/0003-2697(69)90168-7. [DOI] [PubMed] [Google Scholar]
  5. Calvo J. M., Freundlich M., Umbarger H. E. Regulation of branched-chain amino acid biosynthesis in Salmonella typhimurium: isolation of regulatory mutants. J Bacteriol. 1969 Mar;97(3):1272–1282. doi: 10.1128/jb.97.3.1272-1282.1969. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Fangman W. L., Nass G., Neidhardt F. C. Immunological and chemical studies of phenylalanyl sRNA synthetase from Escherichia coli. J Mol Biol. 1965 Aug;13(1):202–219. doi: 10.1016/s0022-2836(65)80090-0. [DOI] [PubMed] [Google Scholar]
  7. Fenster E. D., Anker H. S. Incorporation into polypeptide and charging on transfer ribonucleic acid of the amino acid analog 5',5',5'-trifluoroleucine by leucine auxotrophs of Escherichia coli. Biochemistry. 1969 Jan;8(1):269–274. doi: 10.1021/bi00829a038. [DOI] [PubMed] [Google Scholar]
  8. Fowden L., Lewis D., Tristram H. Toxic amino acids: their action as antimetabolites. Adv Enzymol Relat Areas Mol Biol. 1967;29:89–163. doi: 10.1002/9780470122747.ch3. [DOI] [PubMed] [Google Scholar]
  9. Kohlhaw G., Leary T. R., Umbarger H. E. Alpha-isopropylmalate synthase from Salmonella typhimurium. Purification and properties. J Biol Chem. 1969 Apr 25;244(8):2218–2225. [PubMed] [Google Scholar]
  10. LOWRY O. H., ROSEBROUGH N. J., FARR A. L., RANDALL R. J. Protein measurement with the Folin phenol reagent. J Biol Chem. 1951 Nov;193(1):265–275. [PubMed] [Google Scholar]
  11. MOYED H. S. Interference with feedback control of enzyme activity. Cold Spring Harb Symp Quant Biol. 1961;26:323–329. doi: 10.1101/sqb.1961.026.01.039. [DOI] [PubMed] [Google Scholar]
  12. RICHMOND M. H. The effect of amino acid analogues on growth and protein synthesis in microorganisms. Bacteriol Rev. 1962 Dec;26:398–420. doi: 10.1128/br.26.4.398-420.1962. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Rabinovitz M., Finkleman A., Reagan R. L., Breitman T. R. Amino acid antagonist death in Escherichia coli. J Bacteriol. 1969 Jul;99(1):336–338. doi: 10.1128/jb.99.1.336-338.1969. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. SMITH S. S., BAYLISS N. L., MCCORD T. J. THE SYNTHESIS AND BIOLOGICAL ACTIVITIES OF SOME AZA ANALOGS OF AMINO ACIDS. I. 4-AZALEUCINE, AN INHIBITORY ANALOG OF LEUCINE. Arch Biochem Biophys. 1963 Aug;102:313–315. doi: 10.1016/0003-9861(63)90185-1. [DOI] [PubMed] [Google Scholar]
  15. Schlesinger S., Schlesinger M. J. The effect of amino acid analogues on alkaline phosphatase formation in Escherichia coli K-12. I. Substitution of triazolealanine for histidine. J Biol Chem. 1967 Jul 25;242(14):3369–3372. [PubMed] [Google Scholar]
  16. Silbert D. F., Fink G. R., Ames B. N. Histidine regulatory mutants in Salmonella typhimurium 3. A class of regulatory mutants deficient in tRNA for histidine. J Mol Biol. 1966 Dec 28;22(2):335–347. doi: 10.1016/0022-2836(66)90136-7. [DOI] [PubMed] [Google Scholar]
  17. Taylor R. T., Jenkins W. T. Leucine aminotransferase. I. Colorimetric assays. J Biol Chem. 1966 Oct 10;241(19):4391–4395. [PubMed] [Google Scholar]
  18. Yaniv M., Gros F. Studies on valyl-tRNA synthetase and tRNA from Escherichia coli. I. Purification and properties of the enzyme from normal Escherichia coli strains. J Mol Biol. 1969 Aug 28;44(1):1–15. doi: 10.1016/0022-2836(69)90401-x. [DOI] [PubMed] [Google Scholar]

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