Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:1.2.1.13 (glyceraldehyde-3-phosphate dehydrogenase)
6,511 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Multilocus sequence typing (MLST) was used to obtain insights into the genetic relationships between 14 vancomycin-resistant Enterococcus faecium (VREF) isolates from humans (hospitalized patients, 5 strains) and nonhuman sources (meat and poultry, 9 strains) in northern Italy over the period 1993-2001. The typing scheme (Homan et al., 2002, J. Clin. Microb., 40:1963-1971) based on seven housekeeping genes--adk (adenylate kinase), atpA (ATP synthase, alpha subunit), ddl (D-alanine-D-alanine ligase), gyd (glyceraldehyde-3-phosphate dehydrogenase), gdh (glucose-6-phosphate dehydrogenase), purK (phosphoribosylaminoimidazole carboxylase ATPase subunit), and pstS (phosphate ATP-binding cassette transporter)--was used. In the 14 VREF analyzed, the number of unique alleles ranged from 1 (gyd) to 8 (atpA). Isolates from hospitalized patients were defined by the unique allele purK 1. Nine sequence types (STs) were identified. All of the epidemic strains isolated over the period 2000-2001 showed identical or closely related pulsed-field gel electrophoresis (PFGE) patterns and clustered in the same ST78. These strains shared six of the seven alleles with the strain CA20 representative of the 1993-1999 outbreaks, which PFGE indicated as being unrelated to those of the recent outbreaks. MLST confirmed the unrelatedness of human and nonhuman strains already detected by PFGE. All isolates clustered in three main genetic lineages: group A comprised two of the three isolates from meat; group C the human strains of all outbreaks and one poultry strain; and group B four of the five poultry strains and one meat strain. All human strains carried the esp gene and clustered in the C1 sublineage that has been described as having emerged recently worldwide.
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PMID:Vancomycin-resistant Enterococcus faecium isolates causing hospital outbreaks in northern Italy belong to the multilocus sequence typing C1 lineage. 1525 26

Obesity-related diseases such as the metabolic syndrome and type 2 diabetes originate, in part, from the progressive metabolic deterioration of skeletal muscle. A preliminary proteomic survey of rectus abdominus muscle detected a statistically significant increase in adenylate kinase (AK)1, glyceraldehyde-3-phosphate dehydrogenase (GAPDH), and aldolase A in obese/overweight and morbidly obese women relative to lean control subjects. AK1 is essential for the maintenance of cellular energy charge, and GAPDH and aldolase A are well known glycolytic enzymes. We found that muscle AK1 protein and enzymatic activity increased 2.9 and 90%, respectively, in obese women and 9.25 and 100%, respectively, in morbidly obese women. The total enzymatic activity of creatine kinase, which also regulates energy metabolism in muscle, was shown to increase 30% in obese/overweight women only. We propose that increased protein and enzymatic activity of AK1 is representative of a compensatory glycolytic drift to counteract reduced muscle mitochondrial function with the progression of obesity. This hypothesis is supported by increased abundance of the glycolytic enzymes GAPDH and aldolase A in obese and morbidly obese muscle. In summary, proteome analysis of muscle has helped us better describe the molecular etiology of obesity-related disease.
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PMID:Proteome analysis of skeletal muscle from obese and morbidly obese women. 1585 11

To examine the role of the C-terminal domain in the chaperone function of trigger factor (TF), a number of truncation mutants were constructed, namely: TF419, TF389, TF380, TF360, TF344, and TF251, in which the C-terminal 13, 43, 52, 72, 88 residues or the entire C-domain were deleted, respectively. Co-expression of mutant chicken adenylate kinase (AK) with TF and the C-terminal truncation mutants was achieved using a plasmid pBVAT that allows expression of TF and AK from a single plasmid. The results show that truncation of the C-terminus of TF has only minor effect on its ability to assist AK refolding in vivo. Further, ribosome-binding experiments indicate that C-terminal truncation mutants can still bind to the ribosome and the presence of the C-terminus may in fact lower the affinity of TF for the ribosome in vivo. This indicates that the C-domain of trigger factor may not be essential for the ribosome-associated molecular chaperone function of TF. However, the purified TF C-terminal truncation mutants had a dramatically reduced ability to assist rabbit muscle GAPDH refolding in vitro and a reduced tendency to dimerize. This shows that the structural integrity of the C-terminus contributes to both the chaperone function of TF and the stability of the dimeric form.
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PMID:Effect of C-terminal truncation on the molecular chaperone function and dimerization of Escherichia coli trigger factor. 1638 Feb

It is doubtful that diffusion can deliver sufficient ATP from the mitochondria to sustain activity at the distal end of the sperm flagellum. Glycolytic enzymes bound to the fibrous sheath could provide energy along the flagellum at the point it is required. An obligatory role for glycolysis is supported by the lack of progressive motility in sperm from mice where the gene for sperm-specific glyceraldehyde-3-phosphate dehydrogenase (GAPDHs) had been 'knocked out'. Here, I review some evidence against this idea. First, pure diffusion from the mitochondrion is likely to be adequate in species with smaller sperm, and it is possible that rapid ATP delivery required in larger sperm could be achieved by an adenylate kinase shuttle. Second, experience with alpha-chlorohydrin demonstrates that sperm can remain motile with normal ATP concentrations despite inhibition of GAPDHs; adverse effects only occur if glucose is added and high levels of glycolytic intermediates accumulate. These observations undermine the GAPDHs knockout mouse as evidence for an essential role of local glycolysis. Third, sperm from many species can remain motile for long periods in sugar-free media and excepting dog sperm, evidence that gluconeogenesis is a possible explanation, is weak. In most species, it is unlikely that local glycolysis is the only way that ATP can be supplied to the distal flagellum.
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PMID:Glycolysis and sperm motility: does a spoonful of sugar help the flagellum go round? 1640 53

The flagellum of a mammalian spermatozoon consists of an axoneme surrounded in distinct regions by accessory structures known as the fibrous sheath, outer dense fibers, and the mitochondrial sheath. Although the characterization of individual proteins has provided clues about the roles of these accessory structures, a more complete understanding of flagellar function requires the identification of all the polypeptides in these assemblies. Epididymal mouse sperm were treated with SDS to dislodge sperm heads and to extract the axoneme and membranous elements. The remaining flagellar accessory structures were purified by sucrose gradient centrifugation. Analysis of proteins from these structures by two-dimensional gel electrophoresis and colloidal Coomassie Blue staining showed a highly reproducible pattern of >200 spots. Individual spots were picked, digested with trypsin, and identified by mass spectrometry and peptide microsequencing. Approximately 50 individual proteins were identified that could be assigned to five general categories: 1) proteins previously reported to localize to the accessory structures, e.g. ODF2 in the outer dense fibers, the sperm-specific glyceraldehyde-3-phosphate dehydrogenase in the fibrous sheath, and glutathione peroxidase in the mitochondrial sheath, validating this proteomic approach; 2) proteins that had not been shown to localize to any accessory structure but would be predicted to be present, e.g. glycolytic enzymes; 3) proteins known to be part of the flagellum but not localized to a specific site, e.g. adenylate kinase; 4) proteins not expected to be part of the accessory structures based on their previously reported locations, e.g. tektins; and 5) unknown proteins for which no information is available to make a determination as to location. The unexpected presence of the tektins in the accessory structures of the flagellum was confirmed by both immunoblot and immunofluorescence analysis. This proteomic analysis identified a number of unexpected and novel proteins in the accessory structures of the mammalian flagellum.
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PMID:Proteomic profiling of accessory structures from the mouse sperm flagellum. 1645 89

Poly-tRNA theory have revealed that the tRNA gene-clusters in the Bacillus subtilis trrnD- and rrnB-operons are relics of early peptide-synthesizing RNA apparatus. The trrnD-type and rrnB-type poly-tRNA models were re-analyzed by using recent databases. The results elucidated that the 16 amino acid (aa)-trrnD- and the 21 aa-rrnB-peptides (whose aa sequences are in the order of aa specificities of tRNAs in the respective tRNA cluster) are really relics of earliest peptides encoded by most primitive mRNAs, trrnD-mRNA and rrnB-mRNA, which are homologous to tRNA(Gly) and tRNA(His), respectively. Genes encoding various protein superfamilies (including pgtB protein, glycyl-tRNA synthetase alpha, C-type lectin, F1-ATP-synthase gamma, etc) were concluded to have derived from tRNA(Gly)-tRNA(Cys)-tRNA(Leu) region (including trrnD-mRNA region) in the trrnD-poly-tRNA. Genes for another group of protein superfamilies (including adenylate kinase, glyceraldehyde-3-phosphate dehydrogenase, helix-turn-helix DNA-binding domains, etc.) were found to have derived rrnB-mRNA, which is most plausibly homologous to a region containing the tRNA(His) of the rrnB-poly-tRNA. Thus Proto-tRNA((Gly)) reconstructed from tRNA(Gly) and other tRNAs strongly suggested that proto-tRNA was most plausibly a viroid-like possibly self-cleavable replicable ribozyme possessing a possible hammerhead-like structure.
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PMID:Evolution from possible primitive tRNA-viroids to early poly-tRNA-derived mRNAs: a new approach from the poly-tRNA theory. 1690 Oct 93

Measurement of cell membrane integrity has been widely used to assess chemical cytotoxity. Several assays are available for determining cell membrane integrity including differential labeling techniques using neutral red and trypan blue dyes or fluorescent compounds such as propidium iodide. Other common methods for assessing cytotoxicity are enzymatic "release" assays which measure the extra-cellular activities of lactate dehydrogenase (LDH), adenylate kinase (AK), or glyceraldehyde-3-phosphate dehydrogenase (GAPDH) in culture medium. However, all these assays suffer from several practical limitations, including multiple reagent additions, scalability, low sensitivity, poor linearity, or requisite washes and medium exchanges. We have developed a new cytotoxicity assay which measures the activity of released intracellular proteases as a result of cell membrane impairment. It allows for a homogenous, one-step addition assay with a luminescent readout. We have optimized and miniaturized this assay into a 1536-well format, and validated it by screening a library of known compounds from the National Toxicology Program (NTP) using HEK 293 and human renal mesangial cells by quantitative high-throughput screening (qHTS). Several known and novel membrane disrupters were identified from the library, which indicates that the assay is robust and suitable for large scale library screening. This cytotoxicity assay, combined with the qHTS platform, allowed us to quickly and efficiently evaluate compound toxicities related to cell membrane integrity.
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PMID:A bioluminescent cytotoxicity assay for assessment of membrane integrity using a proteolytic biomarker. 1840 Apr 64

The present study utilized samples from bilateral motor branches of the femoral nerve, as well as saphenous nerves, ventral roots, and dorsal roots of the spinal cord, to detect differential protein expression using two-dimensional gel electrophoresis and nano ultra-high performance liquid chromatography electrospray ionization mass spectrometry tandem mass spectrometry techniques. A mass spectrum was identified using the Mascot search. Results revealed differential expression of 11 proteins, including transgelin, Ig kappa chain precursor, plasma glutathione peroxidase precursor, an unnamed protein product (gi|55628), glyceraldehyde-3-phosphate dehydrogenase-like protein, lactoylglutathione lyase, adenylate kinase isozyme 1, two unnamed proteins products (gi|55628 and gi|1334163), and poly(rC)-binding protein 1 in motor and sensory nerves. Results suggested that these proteins played roles in specific nerve regeneration following peripheral nerve injury and served as specific markers for motor and sensory nerves.
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PMID:Protein expression of sensory and motor nerves: Two-dimensional gel electrophoresis and mass spectrometry. 2577 77

Slightly acidic electrolysed water (SlAEW) and acidic electrolysed water (AEW) have been demonstrated to effectively inactivate food-borne pathogens. However, the underlying mechanism of inactivation remains unknown. Therefore, in this study, a differential proteomic platform was used to investigate the bactericidal mechanism of SlAEW, AEW, and sodium hypochlorite (NaOCl) solutions against Vibrio parahaemolyticus. The upregulated proteins after SlAEW, AEW, and NaOCl treatments were identified as outer membrane proteins K and U. The downregulated proteins after the SlAEW, AEW, and NaOCl treatments were identified as adenylate kinase, phosphoglycerate kinase, glyceraldehyde-3-phosphate dehydrogenase (GAPDH), and enolase, all of which are responsible for energy metabolism. Protein synthesis-associated proteins were downregulated and identified as elongation factor Tu and GAPDH. The inhibitory effects of SlAEW and AEW solutions against V. parahaemolyticus may be attributed to the changes in cell membrane permeability, protein synthesis activity, and adenosine triphosphate (ATP) biosynthesis pathways such as glycolysis and ATP replenishment.
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PMID:Differential proteomics to explore the inhibitory effects of acidic, slightly acidic electrolysed water and sodium hypochlorite solution on Vibrio parahaemolyticus. 2647 89

Sarcosine is an N-methyl derivative of the amino acid glycine, and its elevation in tissues and physiological fluids of patients with sarcosinemia could reflect a deficient pool size of activated 1-carbon units. Sarcosinemia is a rare inherited metabolic condition associated with mental retardation. In the present study, we investigated the acute effect of sarcosine and/or creatine plus pyruvate on some parameters of oxidative stress and energy metabolism in cerebral cortex homogenates of 21-day-old Wistar rats. Acute administration of sarcosine induced oxidative stress and diminished the activities of adenylate kinase, GAPDH, complex IV, and mitochondrial and cytosolic creatine kinase. On the other hand, succinate dehydrogenase activity was enhanced in cerebral cortex of rats. Moreover, total sulfhydryl content was significantly diminished, while DCFH oxidation, TBARS content, and activities of SOD and GPx were significantly enhanced by acute administration of sarcosine. Co-administration of creatine plus pyruvate was effective in the prevention of alterations provoked by sarcosine administration on the oxidative stress and the enzymes of phosphoryltransfer network. These results indicate that acute administration of sarcosine may stimulate oxidative stress and alter the energy metabolism in cerebral cortex of rats. In case these effects also occur in humans, they may contribute, along with other mechanisms, to the neurological dysfunction of sarcosinemia, and creatine and pyruvate supplementation could be beneficial to the patients.
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PMID:Evaluation of Oxidative Stress Parameters and Energy Metabolism in Cerebral Cortex of Rats Subjected to Sarcosine Administration. 2735 17


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