Inhibition of Escherichia coli isoleucine biosynthesis by isoleucine tetrazole.
Growth of a derivative of Escherichia coli K-10 was strongly inhibited by 2 times 10(-4) M L-5(1-amino-2-methylbutyl)-tetrazole (isoleucine tetrazole). Growth inhibition was reversed by isoleucine, threonine, glycyl-L-isoleucine, or glycyl-L-threonine, and, in a valine-resistant mutant, by L-valine. Partial reversal of growth inhibiton was effected by L-leucine, L-methionine, or L-homoserine. The tetrazole inhibited the activity of the biosynthetic threonine deaminase (EC 4.2.1.16 L-threonine hydrolyase [deaminating]), the inhibition being relieved by L-valine. The tetrazole also inhibited isoleucyl-transfer ribonucleic acid (tRNA) synthetase (EC 6.1.1.5 L-isoleucine: tRNA ligase [adenosine monophosphate]), but was without effect on the activities of alpha-isopropylmalate synthetase or acetohydroxy acid synthetase. One class of isoleucine tetrazole-resistant mutants produced biosynthetic threonine deaminases which were no longer subject to feedback inhibition by either isoleucine or the tetrazole.
D015079:2-Isopropylmalate Synthase / Q000378:metabolism; D000095:Acetolactate Synthase / Q000378:metabolism; D001393:Azoles / Q000494:pharmacology*; D003864:Depression, Chemical; D004352:Drug Resistance, Microbial; D004926:Escherichia coli / Q000254:growth & development / Q000378:metabolism*; D006714:Homoserine / Q000494:pharmacology; D007532:Isoleucine / Q000031:analogs & derivatives / Q000096:biosynthesis* / Q000494:pharmacology; D007533:Isoleucine-tRNA Ligase / Q000378:metabolism; D026901:Membrane Transport Proteins / Q000378:metabolism; D008715:Methionine / Q000494:pharmacology; D009154:Mutation; D010455:Peptides / Q000494:pharmacology; D013777:Tetrazoles / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D013912:Threonine / Q000494:pharmacology; D013913:Threonine Dehydratase / Q000378:metabolism; D014633:Valine / Q000494:pharmacology
D001393:Azoles; D026901:Membrane Transport Proteins; D010455:Peptides; D013777:Tetrazoles; D007532:Isoleucine; D013912:Threonine; C011002:isoleucine tetrazole; D006714:Homoserine; D008715:Methionine; D000095:Acetolactate Synthase; D015079:2-Isopropylmalate Synthase; D013913:Threonine Dehydratase; D007533:Isoleucine-tRNA Ligase; D014633:Valine