Effect of 4-azaleucine Upon Leucine Metabolism in Salmonella Typhimurium

Overview

Journal J Bacteriol

Publisher American Society for Microbiology

Specialty Microbiology

Date 1971 Oct 1

PMID 4330744

Citations 8

Authors

B Stieglitz

J M Calvo

Affiliations

Soon will be listed here.

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.

Citing Articles

Signalling architectures can prevent cancer evolution.

Ona L, Lachmann M Sci Rep. 2020; 10(1):674.

PMID: 31959809 PMC: 6971087. DOI: 10.1038/s41598-020-57494-w.

Metabolic engineering of Corynebacterium crenatium for enhancing production of higher alcohols.

Su H, Lin J, Wang G Sci Rep. 2016; 6:39543.

PMID: 27996038 PMC: 5172369. DOI: 10.1038/srep39543.

Participation of branched-chain amino acid analogues in multivalent repression.

Wasmuth J, Umbarger H J Bacteriol. 1973; 116(2):562-70.

PMID: 4583240 PMC: 285418. DOI: 10.1128/jb.116.2.562-570.1973.

Linkage map of Salmonella typhimurium, edition IV.

Sanderson K Bacteriol Rev. 1972; 36(4):558-86.

PMID: 4568764 PMC: 408332. DOI: 10.1128/br.36.4.558-586.1972.

Leucyl-transfer ribonucleic acid synthetase from a wild-type and temperature-sensitive mutant of Salmonella typhimurium.

Mikulka T, Stieglitz B, Calvo J J Bacteriol. 1972; 109(2):584-93.

PMID: 4550813 PMC: 285181. DOI: 10.1128/jb.109.2.584-593.1972.

References

FANGMAN W, NASS G, Neidhardt F . Immunological and chemical studies of phenylalanyl sRNA synthetase from Escherichia coli. J Mol Biol. 1965; 13(1):202-19. DOI: 10.1016/s0022-2836(65)80090-0. View

Taylor R, JENKINS W . Leucine aminotransferase. I. Colorimetric assays. J Biol Chem. 1966; 241(19):4391-5. View

SILBERT D, Fink G, Ames B . Histidine regulatory mutants in Salmonella typhimurium 3. A class of regulatory mutants deficient in tRNA for histidine. J Mol Biol. 1966; 22(2):335-47. DOI: 10.1016/0022-2836(66)90136-7. View

Schlesinger S, SCHLESINGER M . 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; 242(14):3369-72. View

ARGOUDELIS A, HERR R, Mason D, Pyke T, Zieserl J . New amino acids from Streptomyces. Biochemistry. 1967; 6(1):165-70. DOI: 10.1021/bi00853a027. View

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. View

Calvo J, Freundlich M, Umbarger H . Regulation of branched-chain amino acid biosynthesis in Salmonella typhimurium: isolation of regulatory mutants. J Bacteriol. 1969; 97(3):1272-82. PMC: 249844. DOI: 10.1128/jb.97.3.1272-1282.1969. View

FENSTER E, ANKER H . 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; 8(1):269-74. DOI: 10.1021/bi00829a038. View

Calvo J, Bartholomew J, Stieglitz B . Fluorometric assay of enzymatic reactions involving acetyl Coenzyme A in aldol condensations. Anal Biochem. 1969; 28(1):164-81. DOI: 10.1016/0003-2697(69)90168-7. View

10.

KOHLHAW G, Leary T, Umbarger H . Alpha-isopropylmalate synthase from Salmonella typhimurium. Purification and properties. J Biol Chem. 1969; 244(8):2218-25. View

11.

Rabinovitz M, Finkleman A, REAGAN R, BREITMAN T . Amino acid antagonist death in Escherichia coli. J Bacteriol. 1969; 99(1):336-8. PMC: 250007. DOI: 10.1128/jb.99.1.336-338.1969. View

12.

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; 44(1):1-15. DOI: 10.1016/0022-2836(69)90401-x. View

13.

ALEXANDER R, Calvo J, Freundlich M . Mutants of Salmonella typhimurium with an altered leucyl-transfer ribonucleic acid synthetase. J Bacteriol. 1971; 106(1):213-20. PMC: 248664. DOI: 10.1128/jb.106.1.213-220.1971. View

14.

LOWRY O, ROSEBROUGH N, FARR A, RANDALL R . Protein measurement with the Folin phenol reagent. J Biol Chem. 1951; 193(1):265-75. View

15.

Richmond M . The effect of amino acid analogues on growth and protein synthesis in microorganisms. Bacteriol Rev. 1962; 26:398-420. PMC: 441162. DOI: 10.1128/br.26.4.398-420.1962. View

16.

Smith S, BAYLISS N, McCord T . THE SYNTHESIS AND BIOLOGICAL ACTIVITIES OF SOME AZA ANALOGS OF AMINO ACIDS. I. 4-AZALEUCINE, AN INHIBITORY ANALOG OF LEUCINE. Arch Biochem Biophys. 1963; 102:313-5. DOI: 10.1016/0003-9861(63)90185-1. View

17.

BURNS R, Umbarger H, Gross S . THE BIOSYNTHESIS OF LEUCINE. III. THE CONVERSION OF ALPHA-HYDROXY-BETA-CARBOXYISOCAPROATE TO ALPHA-KETOISOCAPROATE. Biochemistry. 1963; 2:1053-8. DOI: 10.1021/bi00905a024. View

18.

Moyed H . Interference with feedback control of enzyme activity. Cold Spring Harb Symp Quant Biol. 1961; 26:323-9. DOI: 10.1101/sqb.1961.026.01.039. View