Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0038187 (starvation)
 24,951 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In Salmonella typhimurium and Escherichia coli, the hemA gene encodes the enzyme glutamyl-tRNA reductase, which catalyzes the first committed step in the heme biosynthetic pathway. It has recently been reported that a lac operon fusion to the hemA promoter of E. coli is induced 20-fold after starvation for heme. Induction was dependent on the transcriptional regulator ArcA, with a second transcriptional regulator, FNR, playing a negative role specifically under anaerobic conditions (S. Darie and R. P. Gunsalus, J. Bacteriol. 176:5270-5276, 1994). We have investigated the generality of this effect by examining the response to heme starvation of a number of lac operon fusions to the hemA promoters of both E. coli and S. typhimurium. We confirmed that such fusions are induced during starvation of a hemA auxotroph, but the level of induction observed was maximally sixfold and for S. typhimurium fusions it was only two- to fourfold. Sequences required for high-level expression of hemA lie within 129 bp upstream of the major (P1) promoter transcriptional start site. Mutants defective in the P1 promoter had greatly reduced hemA-lac expression both in the presence and in the absence of ALA. Mutations in arcA had no effect on hemA-lac expression in E. coli during normal growth, although the increase in expression during starvation for ALA was half that seen in an arcA+ strain. Overexpression of the arcA gene had no effect on hemA-lac expression. Primer extension analysis showed that RNA 5' ends mapping to the hemA P1 and P2 promoters were not expressed at significantly higher levels in induced cultures. These results differ from those previously reported.
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PMID:Transcription of the glutamyl-tRNA reductase (hemA) gene in Salmonella typhimurium and Escherichia coli: role of the hemA P1 promoter and the arcA gene product. 855 Apr 94

In Salmonella typhimurium and Escherichia coli, the hemA gene encodes the enzyme glutamyl-tRNA reductase, which catalyzes the first committed step in heme biosynthesis. We report that when heme limitation is imposed on cultures of S. typhimurium, glutamyl-tRNA reductase (HemA) enzyme activity is increased 10- to 25-fold. Heme limitation was achieved by a complete starvation for heme in hemB, hemE, and hemH mutants or during exponential growth of a hemL mutant in the absence of heme supplementation. Equivalent results were obtained by both methods. To determine the basis for this induction, we developed a panel of monoclonal antibodies reactive with HemA, which can detect the small amount of protein present in a wild-type strain. Western blot (immunoblot) analysis with these antibodies reveals that the increase in HemA enzyme activity during heme limitation is mediated by an increase in the abundance of the HemA protein. Increased HemA protein levels were also observed in heme-limited cells of a hemL mutant in two different E. coli backgrounds, suggesting that the observed regulation is conserved between E. coli and S. typhimurium. In S. typhimurium, the increase in HemA enzyme and protein levels was accompanied by a minimal (less than twofold) increase in the expression of hemA-lac operon fusions; thus HemA regulation is mediated either at a posttranscriptional step or through modulation of protein stability.
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PMID:Regulation of heme biosynthesis in Salmonella typhimurium: activity of glutamyl-tRNA reductase (HemA) is greatly elevated during heme limitation by a mechanism which increases abundance of the protein. 913 7