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)

delta 1-pyrroline-5-carboxylate reductase (P5CR; [L-proline: NAD(P+) 5-oxidoreductase]; EC 1.5.1.2) catalyzes the final step in proline biosynthesis. We have shown that the proline-1 (pro-1) locus of Neurospora crassa encodes P5CR. The pro-1 gene was localized to a 3.2 kb region by complementation of (restoration of proline-independent growth to) a proline auxotroph carrying a recessive mutation at the pro-1 locus. The nucleotide sequence of this 3.2 kb region contains an open reading frame with coding capacity of 311 amino acids. The deduced polypeptide shows significant similarity to P5CR amino acid sequences. Similarity of N. crassa P5CR is greatest to that of the yeast, Saccharomyces cerevisiae, but is also strong to P5CR sequences from archaea, eubacteria, plants, and humans. In N. crassa, amino acid imbalance, including deficiency or excess of a single amino acid, such as histidine, induces expression of many amino acid biosynthetic genes that are under cross-pathway control, a general regulatory system analogous to general amino acid control in Saccharomyces. Although P5CR catalyzes the only committed step in proline biosynthesis, pro-1 expression was unaltered by histidine starvation and independent of CPC1, a positively acting transcription factor that mediates cross-pathway control in N. crassa.
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PMID:Molecular characterization of the proline-1 (pro-1) locus of Neurospora crassa, which encodes delta 1-pyrroline-5-carboxylate reductase. 756 96

The ability of invading pathogens to proliferate within host tissues requires the capacity to resist the killing effects of a wide variety of host defense molecules. sap mutants of the facultative intracellular parasite Salmonella typhimurium exhibit hypersensitivity to antimicrobial peptides, cannot survive within macrophages in vitro and are attenuated for mouse virulence in vivo. We conducted a molecular genetic analysis of the sapG locus and showed that it encodes a product that is 99% identical to the NAD+ binding protein TrkA, a component of a low-affinity K+ uptake system in Escherichia coli. SapG exhibits similarity with other E. coli proteins implicated in K+ transport including KefC, a glutathione-regulated efflux protein, and Kch, a putative transporter similar to eukaryotic K+ channel proteins, sapG mutants were killed by the antimicrobial peptide protamine in the presence of both high and low K+, indicating that protamine hypersensitivity is not due to K+ starvation. Strains with mutations in sapG and either sapJ or the sapABCDF operon were as susceptible as sapG single mutants, suggesting that the proteins encoded by these loci participate in the same resistance pathway. SapG may modulate the activities of SapABCDF and SapJ to mediate the transport of peptides and potassium.
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PMID:A Salmonella protein that is required for resistance to antimicrobial peptides and transport of potassium. 807 92

Under a limited set of hitherto incompletely defined conditions, inhibition of respiration has been shown to cause transient oscillations in NAD(P)H fluorescence of yeast cells. In this paper, we apply a new method [1992, Anal. Biochem. 204, 118-132] for extraction of intracellular metabolites. This method involves spraying the cells into -40 degrees C methanol; the neutral pH allows extraction of nearly all intracellular metabolites, including NADH. Close to the shift from glucose to ethanol as a growth substrate, the cells acquire a make-up amenable to sustained oscillations in intracellular concentrations of NADH and glycolytic intermediates such as glucose-6-phosphate. NADH was found to oscillate between 200 microM and 400 microM intracellular concentration. The cellular make-up determining the tendency to oscillate is 'remembered' by the cells after three hours of starvation.
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PMID:Around the growth phase transition S. cerevisiae's make-up favours sustained oscillations of intracellular metabolites. 843 31

Phosphoribosyl diphosphate-lacking (delta prs) mutant strains of Escherichia coli require NAD, guanosine, uridine, histidine, and tryptophan for growth. NAD is required by phosphoribosyl diphosphate-lacking mutants because of lack of one of the substrates for the quinolinate phosphoribosyltransferase reaction, an enzyme of the NAD de novo pathway. Several NAD-independent mutants of a host from which prs had been deleted were isolated; all of them were shown to have lesions in the pstSCAB-phoU operon, in which mutations lead to derepression of the Pho regulon. In addition NAD-independent growth was dependent on a functional quinolinate phosphoribosyltransferase. The prs suppressor mutations led to the synthesis of a new phosphoryl compound that may act as a precursor for a new NAD biosynthetic pathway. This compound may be synthesized by the product of an unknown phosphate starvation-inducible gene of the Pho regulon because the ability of pst or phoU mutations to suppress the NAD requirement requires PhoB, the transcriptional activator of the Pho regulon.
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PMID:Phosphoribosyl diphosphate synthetase-independent NAD de novo synthesis in Escherichia coli: a new phenotype of phosphate regulon mutants. 855 May 5

In differentiated tissues, such as muscle and brain, increased adenosine monophosphate (AMP) levels stimulate glycolytic flux rates. In the breast cancer cell line MCF-7, which characteristically has a constantly high glycolytic flux rate, AMP induces a strong inhibition of glycolysis. The human breast cancer cell line MDA-MB-453, on the other hand, is characterized by a more differentiated metabolic phenotype. MDA-MB-453 cells have a lower glycolytic flux rate and higher pyruvate consumption than MCF-7 cells. In addition, they have an active glycerol 3-phosphate shuttle. AMP inhibits cell proliferation as well as NAD and NADH synthesis in both MCF-7 and MDA-MB-453 cells. However, in MDA-MB-453 cells glycolysis is slightly activated by AMP. This disparate response of glycolytic flux rate to AMP treatment is presumably caused by the fact that the reduced NAD and NADH levels in AMP-treated MDA-MB-453 cells reduce lactate dehydrogenase but not cytosolic glycerol-3-phosphate dehydrogenase reaction. Due to the different enzymatic complement in MCF-7 cells, proliferation is inhibited under glucose starvation, whereas MDA-MB-453 cells grow under these conditions. The inhibition of cell proliferation correlates with a reduction in glycolytic carbon flow to synthetic processes and a decrease in phosphotyrosine content of several proteins in both cell lines.
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PMID:Effect of extracellular AMP on cell proliferation and metabolism of breast cancer cell lines with high and low glycolytic rates. 903 May 54

The production of some extracellular enzymes is known to be negatively affected by readily metabolized nitrogen sources such as NH4+ although there is no consensus regarding the involved mechanisms. Asparaginase II is a periplasmic enzyme of Saccharomyces cerevisiae encoded by the ASP3 gene. The enzyme activity is not found in cells grown in either ammonia, glutamine, or glutamate, but it is found in cells that have been subjected to nitrogen starvation or have been grown on a poor source of nitrogen such as proline. In this report it is shown that the formation of this enzyme is dependent upon the functional GLN3 gene and that the response to nitrogen availability is under the control of the URE2 gene product. In this respect the expression of ASP3 is similar to the system that regulates the GLN1, GDH2, GAP1, and PUT4 genes that codes for glutamine synthetase, NAD-linked glutamate dehydrogenase, general amino-acid permease, and high affinity proline permease, respectively.
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PMID:Asparaginase II of Saccharomyces cerevisiae. GLN3/URE2 regulation of a periplasmic enzyme. 917 Feb 45

The identification of sigma B-dependent general stress proteins is a useful strategy to understand the physiological role of the unspecific stress response in Bacillus subtilis. By N-terminal sequencing of B. subtilis stress proteins Gsp38 was identified as the NAD-synthetase (NadE). NadE was previously characterized as spore outgrowth factor B (OutB) conferring a temperature-sensitive spore outgrowth defective phenotype. Transcriptional studies showed that nadE is strongly induced in response to heat, ethanol and salt stress or after starvation for glucose in a sigma B-dependent manner. Two promoters are involved in transcriptional initiation, the sigma A-dependent upstream promoter contributes to the basal level during growth, whereas the sigma B-dependent downstream promoter is induced after different stress conditions.
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PMID:The NAD synthetase NadE (OutB) of Bacillus subtilis is a sigma B-dependent general stress protein. 927 69

Four mitochondrial protein kinases have been cloned. These proteins represent a new family of protein kinases, related by sequence to the bacterial protein kinases but by function to the eukaryotic serine protein kinases. Arg288 is required for recognition by BCKDK of the phosphorylation site on the E1alpha subunit of the BCKDH complex. BCKDK inhibits the dehydrogenase activity of the BCKDH complex by introducing a negative charge into the active-site pocket of the E1 component. Protein starvation of rats induces an increase in the amount of BCKDK bound to the BCKDH complex. This causes inactivation of the BCKDH complex and conserves branched-chain amino acids for protein synthesis in the protein-starved state. Expression of the different PDK isoenzymes is tissue specific, and the different PDK isoenzymes are unique with respect to kinetic parameters for ATP and ADP and sensitivity to allosteric effectors (NADH, NAD+, coenzyme A, acetyl-CoA, pyruvate, and dichloroacetate). Preliminary experiments indicate that an increased amount of PDK2 protein partly explains the increase in PDK activity that occurs in rat liver in response to chemically induced diabetes.
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PMID:Mitochondrial alpha-ketoacid dehydrogenase kinases: a new family of protein kinases. 934 45

The nucleotide sequence of the gene encoding the glucose-regulated protein 78 (GRP78) of Neurospora crassa was determined. The ORF codes for a protein of 662 amino acids (72 kDa) and belongs to the heat shock protein 70 (hsp70) gene family, which is characterized by three HSP70 'signature sequences'. The grp78 gene contains 5 introns. The protein carries the ER retention signal HDEL at its carboxy terminus and is most homologous to the KAR2/GRP78 protein of Saccharomyces cerevisiae (78%) and to KAR2/BiP of Yarrowia lipolytica (76%). The expression of grp78 is constitutive and can be enhanced by starvation, treatment with tunicamycin, the calcium ionophore A23187 or elevated temperatures (40 degrees C). An uninterrupted ORF was found on the reverse cDNA strand of grp78. The putative peptide shows 47% homology to the NAD-specific glutamate dehydrogenase of Achlya klebsiana.
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PMID:Molecular analysis of a glucose-regulated gene (grp78) of Neurospora crassa. 954 20

Bacillus subtilis responds to various stimuli (heat, ethanol and salt stress, energy starvation) with the induction of general stress proteins (GSPs). Most of them belong to the stress and stationary-phase regulon controlled by the alternative sigma factor sigmaB. The majority of sigmaB-dependent proteins are thought to provide a precautionary general stress resistance in stressed or starved cells. In this report, the identification and transcriptional analysis of nine new members of the sigmaB regulon are described. The biochemical function was not determined for any of the proteins encoded by the nine new sigmaB-dependent stress genes, however, similarities to proteins in the databases allowed a distinction between proteins with putative (i-iv) and unknown (v) function. The putative functions of BmrU, YcdF, YdaD, YdaP, YhdN and YocK underline the suggested protective role of sigmaB-dependent GSPs and also elucidate new areas where sigmaB might play an important role. (i) The finding that the bmrUR operon is under sigmaB control indicates that the elimination of multidrug compounds might be a new function in multiple stress resistance. (ii) YcdF and YdaD resemble NAD(P)-dependent dehydrogenases. Both proteins could be involved in the generation of NAD(P)H and therefore in the maintenance of the intracellular redox balance under stress. (iii) The ydaP gene might belong to the increasing number of sigmaB-dependent genes whose orthologues are under the control of sigmas in Escherichia coli, indicating that both regulons may fulfil similar functions. (iv) YhdN shows weak similarities to potassium ion channel proteins and YocK shows resemblance to the DnaK suppressor protein DksA. (v) Three new sigmaB-dependent genes (ydaE, ydaG and yfkM) encoding proteins with still unknown functions were also described. Further analyses of corresponding mutants might allow a first prediction of their function within the framework of the general stress regulon.
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PMID:Identification and transcriptional analysis of new members of the sigmaB regulon in Bacillus subtilis. 1022 Jan 66


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