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Query: UMLS:C0038187 (starvation)
 24,951 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The selenophosphate synthetases from several organisms contain a selenocysteine residue in their active site where the Escherichia coli enzyme contains a cysteine. The synthesis of these enzymes, therefore, depends on their own reaction product. To analyse how this self-dependence is correlated with the selenium status, e.g. after recovery from severe selenium starvation, we expressed the gene for the selenocysteine-containing selenophosphate synthetase from Haemophilus influenzae (selDHI) in an E. coli DeltaselD strain. Gene selDHI gave rise to a selenium-containing gene product and also supported - via its activity - the formation of E. coli selenoproteins. The results provide evidence either for the suppression of the UGASec codon with the insertion of an amino acid allowing the formation of a functional product or for a bypass of the selenophosphate requirement. We also show that the selenocysteine synthesis and the insertion systems of the two organisms are fully compatible despite conspicuous differences in the mRNA recognition motif.
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PMID:Functional expression in Escherichia coli of the Haemophilus influenzae gene coding for selenocysteine-containing selenophosphate synthetase. 939 37

Starvation for sulfate results in increased synthesis of several proteins in Escherichia coli. Among these Ssi (sulfate starvation-induced) proteins are the products of the tauABCD genes, which are required for utilization of taurine as sulfur source for growth. In this study, the role of the cbl gene in expression of tauABCD and other ssi genes was investigated. The protein encoded by cbl shows high sequence similarity to CysB, the LysR-type transcriptional activator of the genes involved in cysteine biosynthesis. Strain EC2541, which contains an internal deletion in cbl, was unable to utilize taurine and other aliphatic sulfonates as sulfur sources. Two-dimensional sodium dodecyl sulfate-polyacrylamide gel electrophoresis showed that many of the Ssi proteins were not synthesized in EC2541. Expression of a translational tauD'-'lacZ fusion required the presence of both cbl and cysB. The interactions of CysB and Cbl with the promoter region of tauABCD were studied by using gel mobility shift experiments and DNase I footprinting. CysB occupied multiple binding sites, whereas Cbl occupied only one site from 112 to 68 bp upstream of the transcription start site. Acetylserine, the inducer of transcription of CysB-regulated genes, stimulated binding of CysB but not of Cbl. Sulfate had no effect on binding of both proteins to the tauABCD promoter region. These results indicate that Cbl is a transcription factor for genes required for sulfonate-sulfur utilization and maybe for other genes whose expression is induced by sulfate starvation.
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PMID:Involvement of CysB and Cbl regulatory proteins in expression of the tauABCD operon and other sulfate starvation-inducible genes in Escherichia coli. 940 Oct 24

The ability of astroglia-rich primary cultures derived from the brains of neonatal rats to take up and metabolize various sulfur containing compounds to cysteine was investigated using the content of intracellular glutathione as an indicator. Astroglial cells were partially depleted of glutathione by starvation for 24 h. Subsequent feeding for 4 h with glucose, glycine, and glutamate resulted in a restoration of the glutathione level, if cysteine was present. Substitution of cysteine by cystine during resynthesis of glutathione led to a glutathione content which exceeded that of cysteine-refed cells by 41%. Half-maximal content of glutathione was found at a concentration of about 12 microM cysteine and a maximal content at a concentration of at least 50 microM cysteine. In contrast, no plateau in the glutathione level was reached with increasing concentrations of cystine. The cystine effect could not be due to a contamination, since it was abolished after reduction of cystine by dithiothreitol. Since the cystine effect was not affected by inhibiting gamma-glutamyl transpeptidase, a promotion of cystine uptake by formation of gamma-glutamylcystine can also be excluded. Of the potential cysteine precursors tested, N-acetylcysteine was able to replace cysteine half-maximally at a concentration of 1 mM and fully at 5 mM. Feeding 2-oxothiazolidine-4-carboxylic acid at a concentration of 5 mM resulted in 64% of the glutathione level found in the presence of cysteine. A half-maximal glutathione content was attained at 50 microM 2-oxothiazolidine-4-carboxylic acid. While cystathionine could partially replace cysteine, methionine and homocysteine were not at all able to substitute for cysteine. These results demonstrate that astroglial cells prefer cystine from cysteine for glutathione synthesis and express uptake systems for N-acetylcysteine, 2-oxothiazolidine-4-carboxylic acid, and cystathionine, as well as the enzymes N-deacetylase, 5-oxoprolinase, and cystathionine gamma-lyase.
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PMID:Utilization of cysteine and cysteine precursors for the synthesis of glutathione in astroglial cultures: preference for cystine. 943 84

Pseudomonas aeruginosa PAO1 grew in defined synthetic medium with any of a broad variety of single sulfur sources, including sulfate, cysteine, thiocyanate, alkanesulfonates, organosulfate esters and methionine, but not with aromatic sulfonates, thiophenols or organothiocyanates or isothiocyanates. During growth with any of these compounds except sulfate, cysteine or thiocyanate, a set of 10 sulfate starvation-induced (SSI) proteins was strongly up-regulated, as observed by two-dimensional protein electrophoresis of total cell extracts. A comparable level of up-regulation was found for the hydrolytic enzyme arylsulfatase, which has previously been used as a marker enzyme for the sulfate starvation response. One of the SSI proteins was identified by N-terminal sequencing as a high-affinity periplasmic sulfate-binding protein, and another was related to thiol-specific antioxidants, but the N-terminal sequences of the other SSI proteins revealed no similarity to N-termini of proteins of known function, and they probably represent uncharacterized enzymes involved in sulfur scavenging when preferred sulfur sources are absent. To study the role that cysteine biosynthetic intermediates play in the synthesis of these proteins in vivo, we isolated mini-Tn5 transposon mutants of P. aeruginosa with insertions in the cysN and cysI genes, which encode subunits of ATP-sulfurylase and sulfite reductase, respectively. These two genes were cloned and sequenced. cysI showed high similarity to the cognate gene in Escherichia coli, whereas cysN encoded a 69.3 kDa protein with two domains corresponding to the E. coli CysN and CysC proteins. Sulfate no longer repressed synthesis of the SSI proteins in cysN mutants, but repression was restored by sulfite; in the cysI mutant, sulfate, sulfite and sulfide all led to repression of SSI protein synthesis. This suggests that there are at least two independent corepressors of the sulfate starvation response in this species.
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PMID:Regulation of the sulfate starvation response in Pseudomonas aeruginosa: role of cysteine biosynthetic intermediates. 961 12

The intracellular content of glutathione in astroglia-rich primary cultures derived from the brains of newborn rats was used as an indicator for the ability of these cultures to utilize cysteinylglycine (CysGly) for glutathione synthesis. After a 24-h starvation period in the absence of glucose and amino acids, CysGly was able to substitute for cysteine plus glycine in the restoration of glutathione. Glutathione restoration from CysGly plus glutamate was only slightly affected by the dipeptides carnosine or serylglycine in a 200-fold excess. Captopril, a substrate of the peptide transporter PepT1, had almost no effect on glutathione restoration. In contrast, with increasing concentrations of alanylalanine or cefadroxil, known substrates of the peptide transporter PepT2, the amount of glutathione restored in the presence of CysGly and glutamate was strongly reduced. Cefadroxil in a 200-fold excess totally prevented the utilization of CysGly for glutathione restoration. The presence of mRNA for PepT2 in astroglia-rich primary cultures was demonstrated by application of RT-PCR. These results demonstrate that PepT2 is expressed in astroglia-rich primary cultures and that this transporter is highly likely to be responsible for the uptake of CysGly in these cultures.
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PMID:The peptide transporter PepT2 mediates the uptake of the glutathione precursor CysGly in astroglia-rich primary cultures. 964 88

Pathogenic Yersinia species have been shown to synthesize a siderophore molecule, yersiniabactin, as a virulence factor during iron starvation. Here we provide the first biochemical evidence for the role of the Yersinia pestis high molecular weight protein 2 (HMWP2), a nonribosomal peptide synthetase homologue, and YbtE in the initiation of yersiniabactin biosynthesis. YbtE catalyzes the adenylation of salicylate and the transfer of this activated salicyl group to the N-terminal aryl carrier protein domain (ArCP; residues 1-100) of HMWP2. A fragment of HMWP2, residues 1-1491, can adenylate cysteine and with the resulting cysteinyl-AMP autoaminoacylate the peptidyl carrier protein domain (PCP1; residues 1383-1491) either in cis or in trans. Catalytic release of hydroxyphenylthiazoline carboxylic acid (HPT-COOH) and/or N-(hydroxyphenylthiazolinylcarbonyl)cysteine (HPT-cys) is observed upon incubation of YbtE, HMWP2 1-1491, L-cysteine, salicylate, and ATP. These products presumably arise from nucleophilic attack by water or cysteine of a stoichiometric hydroxyphenylthiazolinylcarbonyl-S-PCP1-HMWP2 intermediate. Detection of the heterocyclization capacity of HMWP2 1-1491 implies salicyl-transferring and thiazoline-forming activity for the HMWP2 condensation domain (residues 101-544) and is the first demonstration of such heterocyclization ability in a nonribosomal peptide synthetase enzyme.
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PMID:The nonribosomal peptide synthetase HMWP2 forms a thiazoline ring during biogenesis of yersiniabactin, an iron-chelating virulence factor of Yersinia pestis. 970 2

During normal development, cell elimination [1,2] occurs by programmed cell death (PCD) [3], of which apoptosis [4] is the best known morphological type. Activation of cysteine proteases termed caspases [5] is required in many instances of animal PCD [6-9], but its role outside the animal kingdom is as yet unknown. PCD occurs during developmental stages in the slime mold Dictyostelium discoideum [10,11]. Under favorable conditions, Dictyostelium multiplies as a unicellular organism. Upon starvation, a pathway involving aggregation, differentiation and morphogenesis induces the formation of a multicellular fungus-like structure called a sorocarp [12], consisting mainly of spores and stalk cells, the latter being a result of cell death. Dictyostelium cell death is similar to classical apoptosis in that some cytoplasmic and chromatin condensation occurs but differs from apoptosis because it involves massive vacuolisation and, interestingly, lacks DNA fragmentation [11]. We examined whether caspase activity is required for Dictyostelium cell death. We found that caspase inhibitors did not affect cell death, although some caspase inhibitors that did not inhibit cell death impaired other stages in development and could block affinity-labelling of soluble extracts of Dictyostelium cells with an activated caspase-specific reagent. The simplest interpretation of these results is that in Dictyostelium, whether or not caspase-like molecules exist and are required for some developmental steps, caspase activation is not required for cell death itself.
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PMID:Apparent caspase independence of programmed cell death in Dictyostelium. 974 96

The restoration of glutathione in astroglia-rich primary cultures derived from the brains of newborn rats was used to indicate metabolic properties of astroglial cells. At a culture age of 14-21 days these cultures contain an average total glutathione content of 32.8 +/- 3.2 nmol/mg protein and a cytosolic volume, estimated with the 3-O-methylglucose method, of 4.1 +/- 0.1 microl/mg protein. Therefore, cells of astroglial cultures have a cytosolic glutathione concentration of about 8 mM. In order to investigate glutathione synthesis in astroglial cultures the cellular glutathione content was reduced by starvation in a minimal medium lacking glucose and amino acids. Resynthesis of glutathione depended on the presence of glucose and the three constituent amino acids glutamate, cysteine and glycine. Absence of glucose reduced the amount of net glutathione restoration found after 4 h of incubation by about 50%. Of known substrates of astroglial energy metabolism, mannose could fully and fructose, lactate, pyruvate or sorbitol could partially replace glucose during glutathione restoration. In contrast to these compounds, galactose, 5-thioglucose and 2-deoxyglucose failed to substitute for glucose during glutathione restoration. Astroglial cells are able to use as precursors for the three constituent amino acids of glutathione a variety of amino acids and dipeptides. The results presented demonstrate that glutathione restoration can be used as an indicator for amino acid as well as energy metabolism of astroglial cells.
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PMID:Glutathione restoration as indicator for cellular metabolism of astroglial cells. 977 78

When Pseudomonas aeruginosa is grown with organosulfur compounds as sulfur sources, it synthesizes a set of proteins whose synthesis is repressed in the presence of sulfate, cysteine, or thiocyanate (so-called sulfate starvation-induced proteins). The gene encoding one of these proteins, PA13, was isolated from a cosmid library of P. aeruginosa PAO1 and sequenced. It encoded a 381-amino-acid protein that was related to several reduced flavin mononucleotide (FMNH2)-dependent monooxygenases, and it was the second in an operon of three genes, which we have named msuEDC. The MsuD protein catalyzed the desulfonation of alkanesulfonates, requiring oxygen and FMNH2 for the reaction, and showed highest activity with methanesulfonate. MsuE was an NADH-dependent flavin mononucleotide (FMN) reductase, which provided reduced FMN for the MsuD enzyme. Expression of the msu operon was analyzed with a transcriptional msuD::xylE fusion and was found to be repressed in the presence of sulfate, sulfite, sulfide, or cysteine and derepressed during growth with methionine or alkanesulfonates. Growth with methanesulfonate required an intact cysB gene, and the msu operon is therefore part of the cys regulon, since sulfite utilization was found to be CysB independent in this species. Measurements of msuD::xylE expression in cysN and cysI genetic backgrounds showed that sulfate, sulfite, and sulfide or cysteine play independent roles in negatively regulating msu expression, and sulfonate utilization therefore appears to be tightly regulated.
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PMID:A novel reduced flavin mononucleotide-dependent methanesulfonate sulfonatase encoded by the sulfur-regulated msu operon of Pseudomonas aeruginosa. 1004 77

The molecular mechanisms for regulation of the genes involved in the biosynthesis of methionine and cysteine are poorly characterized in Bacillus subtilis. Analyses of the recently completed B. subtilis genome revealed 11 copies of a highly conserved motif. In all cases, this motif was located in the leader region of putative transcriptional units, upstream of coding sequences that included genes involved in methionine or cysteine biosynthesis. Additional copies were identified in Clostridium acetobutylicum and Staphylococcus aureus, indicating conservation in other Gram-positive genera. The motif includes an element resembling an intrinsic transcriptional terminator, suggesting that regulation might be controlled at the level of premature termination of transcription. The 5' portion of all of the leaders could fold into a conserved complex structure. Analysis of the yitJ gene, which is homologous to Escherichia coli metH and metF, revealed that expression was induced by starvation for methionine and that induction was independent of the promoter and dependent on the leader region terminator. Mutation of conserved primary sequence and structural elements supported a model in which the 5' portion of the leader forms an anti-antiterminator structure, which sequesters sequences required for the formation of an antiterminator, which, in turn, sequesters sequences required for the formation of the terminator; the anti-antiterminator is postulated to be stabilized by the binding of some unknown factor when methionine is available. This set of genes is proposed to form a new regulon controlled by a global termination control system, which we designate the S box system, as most of the genes are involved in sulphur metabolism and biosynthesis of methionine and cysteine.
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PMID:The S box regulon: a new global transcription termination control system for methionine and cysteine biosynthesis genes in gram-positive bacteria. 1009 22


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