Regulation of homocysteine biosynthesis in Salmonella typhimurium.
The regulation of the homocysteine branch of the methionine biosynthetic pathway in Salmonella typhimurium has been reexamined with the aid of a new assay for the first enzyme. The activity of this enzyme is subject to synergistic feedback inhibition by methionine plus S-adenosylmethionine. The synthesis of all three enzymes of the pathway is regulated by noncoordinate repression. The enzymes are derepressed in metJ and metK regulatory mutants, suggesting the existence of regulatory elements common to all three. Experiments with a methionine/vitamin B(12) auxotroph (metE) grown in a chemostat on methionine or vitamin B(12) suggested that the first enzyme is more sensitive to repression by methionine derived from exogenous than from endogenous sources. metB and metC mutants grown on methionine in the chemostat did not show hypersensitivity to repression by exogenous methionine. Therefore, it appears that the metE chemostat findings are peculiar to the phenotype of this mutant; such evidence suggests a possible role for a functional methyltetrahydrofolate-homocysteine transmethylase in regulating the synthesis of the first enzyme. Thus there appear to be regulatory elements which are common to the repression of all three enzymes, as well as some that are unique to the first enzyme. The nature of the corepressor is not known, but it may be a derivative of S-adenosylmethionine. metJ and metK mutants of Salmonella have a normal capacity for S-adenosylmethionine synthesis but may be blocked in synthesis or utilization of a corepressor derived from it.
D000217:Acyltransferases / Q000096:biosynthesis; D001431:Bacteriological Techniques; D002247:Carbon Isotopes; D004794:Enzyme Repression; D005246:Feedback; D005827:Genetics, Microbial; D006710:Homocysteine / Q000096:biosynthesis*; D006714:Homoserine; D006836:Hydro-Lyases / Q000096:biosynthesis; D012695:L-Serine Dehydratase / Q000096:biosynthesis; D008190:Lyases / Q000378:metabolism; D008715:Methionine / Q000096:biosynthesis / Q000378:metabolism / Q000494:pharmacology; D008967:Molecular Biology; D009154:Mutation; D012436:S-Adenosylmethionine / Q000494:pharmacology; D012486:Salmonella typhimurium / Q000201:enzymology / Q000378:metabolism*; D013053:Spectrophotometry; D013386:Succinates; D013763:Tetrahydrofolates; D014316:Tritium; D014805:Vitamin B 12 / Q000378:metabolism
D002247:Carbon Isotopes; D013386:Succinates; D013763:Tetrahydrofolates; D006710:Homocysteine; D014316:Tritium; D006714:Homoserine; D012436:S-Adenosylmethionine; D008715:Methionine; D000217:Acyltransferases; D008190:Lyases; D006836:Hydro-Lyases; D012695:L-Serine Dehydratase; D014805:Vitamin B 12