Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:1.2.1.13 (glyceraldehyde-3-phosphate dehydrogenase)
 6,511 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Burchall, J. J. (University of Illinois, Urbana), R. A. Niederman, and M. J. Wolin. Amino group formation and glutamate synthesis in Streptococcus bovis. J. Bacteriol. 88:1038-1044. 1964.-Extracts of Streptococcus bovis grown on NH(4) (+) as a nitrogen source contain a nicotinamide adenine dinucleotide phosphate (NADP)-linked glutamic dehydrogenase and are devoid of alanine dehydrogenase, other amino acid dehydrohygenases, and aspartase. A potential source of reduced nicotinamide adenine dinucleotide phosphate for glutamate synthesis is a NADP and nicotinamide adenine dinucleotide (NAD)-linked glyceraldehyde-3-phosphate dehydrogenase present in the extracts. Experiments with C(14)-labeled glucose and NaHCO(3) indicate that the glutamate carbon skeleton is synthesized by a tricarboxylic acid pathway. The synthesis of the carbon skeleton of glutamate is repressed when glutamate or casein hydrolysate supplement the NH(4) (+)-containing growth medium. Repression of glutamic dehydrogenase and a NAD-linked isocitric dehydrogenase occurs only when complex nitrogen sources, but not when free amino acids, are added to the growth medium.
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PMID:AMINO GROUP FORMATION AND GLUTAMATE SYNTHESIS IN STREPTOCOCCUS BOVIS. 1421 16

Vascularity is increased in placentas from high- compared with low-altitude pregnancies. An angiogenic response to hypoxia may protect an organ from further hypoxic insult by increasing blood flow and oxygen delivery to the tissue. We hypothesized that increased placental vascularity is sufficient to adapt to high altitude. Therefore, indexes of hypoxic stress would not be present in placentas from successful high-altitude pregnancies. Full-thickness placental biopsies were 1) collected and frozen in liquid nitrogen within 5 min of placental delivery and 2) fixed in formalin for stereologic analyses at high (3,100 m, n = 10) and low (1,600 m, n = 10) altitude. Hypoxia-inducible transcription factor (HIF-1) activity was analyzed by ELISA. Western blot analyses were used to evaluate HIF-1alpha, HIF-1beta, HIF-2alpha, von Hippel-Lindau protein, VEGF, Flt-1, enolase, and GAPDH. Magnetic resonance spectroscopy was used to evaluate endogenous metabolism. The ratio of placental capillary surface density to villous surface density was 70% greater at high compared with low altitude. HIF-1 activity and HIF-1-associated proteins were unchanged in placentas from high- vs. low-altitude pregnancies. Placental expression of HIF-1-mediated proteins VEGF, Flt-1, enolase, and GAPDH were unchanged at high vs. low altitude. Succinate, GSH, phosphomonoesters, and ADP were elevated in placenta from high compared with low altitude. Placentas from uncomplicated high-altitude pregnancies have greater vascularity and no indication of significant hypoxic stress at term compared with placentas from low altitude.
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PMID:Greater vascularity, lowered HIF-1/DNA binding, and elevated GSH as markers of adaptation to in vivo chronic hypoxia. 1513 53

The effect of parathyroid hormone (PTH) on the production of osteoprotegerin (OPG) and ligand of receptor activator of NF-kappaB (RANKL) in human bone is incompletely understood. Most in vitro studies indicate that PTH decreases OPG and increases RANKL production. In primary hyperparathyroidism (PHPT), hypersecretion of PTH leads to enhanced bone resorption and formation with increased risk of fracture. Decreasing PTH levels by surgery normalizes bone metabolism, but the effects on skeletal OPG and RANKL production are unknown. In this study, 24 patients referred to our clinic for evaluation, and treatment of PHPT were included. A transiliac bone biopsy was done before (n = 24) and 12 months after parathyroidectomy (PTX) (n = 21). Biopsies were frozen in liquid nitrogen and RNA extracted using Trizol. A competitive RT-PCR assay for RANKL and OPG mRNA using artificial cDNA standards was developed and used for quantification. Results were normalized for GAPDH mRNA content. Before surgery, the RANKL/GAPDH gene expression ratio showed positive correlations with serum osteocalcin (r = 0.42, P < 0.05) and urinary NTX (r = 0.43, P < 0.05). The OPG/GAPDH mRNA levels in iliac bone before surgery correlated with serum osteocalcin (r = 0.52, P < 0.01), but not with bone resorption markers. The mRNA ratio of RANKL/OPG decreased significantly (P < 0.05) after surgery. In conclusion, RANKL and OPG gene expression within the human bone microenvironment are influenced by PTH, as the ratio RANKL/OPG decreased upon PTX. In addition, locally produced RANKL appears to affect bone turnover in the hyperparathyroid state.
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PMID:Skeletal changes in osteoprotegerin and receptor activator of nuclear factor-kappab ligand mRNA levels in primary hyperparathyroidism: effect of parathyroidectomy and association with bone metabolism. 1520 66

Lactococcus lactis grows homofermentatively on glucose, while its growth on maltose under anaerobic conditions results in mixed acid product formation in which formate, acetate, and ethanol are formed in addition to lactate. Maltose was used as a carbon source to study mixed acid product formation as a function of the growth rate. In batch and nitrogen-limited chemostat cultures mixed acid product formation was shown to be linked to the growth rate, and homolactic fermentation occurred only in resting cells. Two of the four lactococcal strains investigated with maltose, L. lactis 65.1 and MG1363, showed more pronounced mixed acid product formation during growth than L. lactis ATCC 19435 or IL-1403. In resting cell experiments all four strains exhibited homolactic fermentation. In resting cells the intracellular concentrations of ADP, ATP, and fructose 1,6-bisphosphate were increased and the concentration of P(i) was decreased compared with the concentrations in growing cells. Addition of an ionophore (monensin or valinomycin) to resting cultures of L. lactis 65.1 induced mixed acid product formation concomitant with decreases in the ADP, ATP, and fructose 1,6-bisphosphate concentrations. ADP and ATP were shown to inhibit glyceraldehyde-3-phosphate dehydrogenase, lactate dehydrogenase, and alcohol dehydrogenase in vitro. Alcohol dehydrogenase was the most sensitive enzyme and was totally inhibited at an adenine nucleotide concentration of 16 mM, which is close to the sum of the intracellular concentrations of ADP and ATP of resting cells. This inhibition of alcohol dehydrogenase might be partially responsible for the homolactic behavior of resting cells. A hypothesis regarding the level of the ATP-ADP pool as a regulating mechanism for the glycolytic flux and product formation in L. lactis is discussed.
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PMID:The pool of ADP and ATP regulates anaerobic product formation in resting cells of Lactococcus lactis. 1534 35

The major damaging factor during and after the ischemic/hypoxic insult is the generation of free radicals, which leads to apoptosis, necrosis, and ultimately cell death. Rubia cordifolia (RC), Fagonia cretica linn (FC), and Tinospora cordifolia (TC) have been reported to contain a wide variety of antioxidants and have been in use in the eastern system of medicine for various disorders. Hippocampal slices were subjected to oxygen-glucose deprivation (OGD) and divided into three groups, control, OGD, and OGD+drug treated. Cytosolic reduced glutathione (GSH), nitric oxide [NO, measured as nitrite (NO2)]. EPR was used to establish the antioxidant effect of RC, FC, and TC with respect to superoxide anion (O*2-), hydroxyl radicals (*OH), nitric oxide (NO) radical, and peroxynitrite anion (ONOO-) generated from pyrogallol, menadione, DETA-NO, and Sin-1, respectively. RT-PCR was performed for the three herbs to assess their effect on the expression of gamma-glutamylcysteine ligase (GCLC), iNOS, and GAPDH gene expression. All the three herbs were effective in elevating the GSH levels and expression of the GCLC. The herbs also exhibited strong free radical scavenging properties against reactive oxygen and nitrogen species as revealed by electron paramagnetic resonance spectroscopy, diminishing the expression of iNOS gene. RC, FC, and TC therefore attenuate oxidative stress mediated cell injury during OGD and exert the above effects at both the cytosolic as well as at gene expression levels and may be effective therapeutic tool against ischemic brain damage.
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PMID:Effect of Rubia cordifolia, Fagonia cretica linn, and Tinospora cordifolia on free radical generation and lipid peroxidation during oxygen-glucose deprivation in rat hippocampal slices. 1547 68

Seedlings of Triticum aestivum L. and Secale cereale L. were grown in the presence of six different (five having different chemical structures) chlorosis-inducing herbicides: aminotriazole and its derivative SDR 5175, haloxidine, Sandoz 6706, fluometuron, and EMD-IT 5914. Concentrations were applied which allowed the leaves to grow normally and to reach normal total amino nitrogen contents but evoked a complete chlorosis (less than 6% chlorophyll). The effects of the herbicides on the accumulation of several chloroplast constituents and on peroxisomal and mitochondrial marker enzyme activities were compared. Wheat and rye, in general, gave very similar results, wheat being more sensitive to unspecific inhibitory effects.In dark-grown plants, the herbicides had no or only minor effects on the rRNA pattern and on enzyme activities of the leaves. In the light, all herbicides applied prevented the accumulation of carotenoids and of chloroplastic rRNA. Consequently, ribulose-1,5-bisphosphate carboxylase activity was virtually absent. After all herbicide treatments in light, the leaves contained only rather low catalase activity. In the presence of aminotriazole and haloxidine, the chloroplast-specific NADP-glyceraldehyde-3-phosphate dehydrogenase and the peroxisomal enzymes glycolate oxidase and hydroxypyruvate reductase had high or even normal activities, as in untreated leaves. In leaves treated with Sandoz 6706, fluometuron, or EMDIT 5914, the activities of the latter three enzymes were, in parallel, only very low. Some herbicides interfered with enzyme activities in vitro, particularly with those of catalase and of glycolate oxidase. Among mitochondrial enzymes, cytochrome c oxidase activity was either unaffected or lower, while fumarase had considerably higher activities in the herbicide-treated, as compared to untreated leaves. The specific effects on peroxisomal enzymes cannot be explained by the hypothesis of herbicide-induced photodestructions in carotene-deficient plastids. Alternative explanations for the genesis of the chlorosis are discussed.
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PMID:Comparative Investigation of the Action of Several Chlorosis-inducing Herbicides on the Biogenesis of Chloroplasts and Leaf Microbodies. 1666 Apr 8

Nitrogen deficiency and the presence of specific organic carbon sources prevent chloroplast development in Euglena. In exponentially growing cultures, chlorophyll levels were low and independent of the nitrogen content of the growth medium. Chlorophyll levels increased in stationary phase and the amount of chlorophyll formed was proportional to the initial nitrogen content of the growth medium; the greater the concentration of nitrogen, the greater the amount of chlorophyll synthesized during stationary phase. Washing experiments demonstrated that the major nutritional factor inhibiting chlorophyll synthesis in stationary phase cultures grown on medium containing a high carbon to nitrogen ratio was the absence of nitrogen rather than the presence of utilizable organic carbon.The light-induced synthesis of chlorophyll and of NADP-glyceraldehyde-3-phosphate dehydrogenase was inhibited when acetate or ethanol was added at the time of exposure of dark-grown resting cells to light. Malate addition, however, stimulated chlorophyll and enzyme synthesis. Both cell number and total cell protein increased after ethanol, acetate, or malate addition, indicating that the resting cells were not nitrogen-deficient. Ethanol and acetate specifically repress light-induced chlorophyll synthesis. NADP-glyceraldehyde-3-phosphate dehydrogenase synthesis was inhibited at a time, the first 24 hours of light exposure, when chlorophyll synthesis was unaffected by carbon addition.
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PMID:Nutritional Regulation of Organelle Biogenesis in Euglena: REPRESSION OF CHLOROPHYLL AND NADP-GLYCERALDEHYDE-3-PHOSPHATE DEHYDROGENASE SYNTHESIS. 1666 Nov 95

Nitric oxide (NO) has been demonstrated to be the principal effector molecule mediating intracellular killing of Leishmania, both in vitro and in vivo. We investigated the type of cell death process induced by NO for the intracellular amastigote stage of the protozoa Leishmania. Specific detection methods revealed a rapid and extensive cell death with morphological features of apoptosis in axenic amastigotes exposed to NO donors, in intracellular amastigotes inside in vitro - activated mouse macrophages and also in activated macrophages of regressive lesions in a leishmaniasis-resistant mouse model. We extended our investigations to the dog, a natural host-reservoir of Leishmania parasites, by demonstrating that co-incubation of infected macrophages with autologous lymphocytes derived from dogs immunised with purified excreted-secreted antigens of Leishmania resulted in a significant NO-mediated apoptotic cell death of intracellular amastigotes. From the biochemical point of view, NO-mediated Leishmania amastigotes apoptosis did not seem to be controlled by caspase activity as indicated by the lack of effect of cell permeable inhibitors of caspases and cysteine proteases, in contrast to specific proteasome inhibitors, such as lactacystin or calpain inhibitor I. Moreover, addition of the products of two NO molecular targets, cis-aconitase and glyceraldehyde-3-phosphate dehydrogenase, also had an inhibitory effect on the cell death induced by NO. Interestingly, activities of these two enzymes plus 6-phosphogluconate dehydrogenase, parasitic enzymes involved in both glycolysis and respiration processes, are overexpressed in amastigotes selected for their NO resistance. This review focuses on cell death of the intracellular stage of the pathogen Leishmania induced by nitrogen oxides and gives particular attention to the biochemical pathways and the molecular targets potentially involved. Questions about the role of Leishmania amastigotes NO-mediated apoptosis in the overall infection process are raised and discussed.
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PMID:Phenotypical characteristics, biochemical pathways, molecular targets and putative role of nitric oxide-mediated programmed cell death in Leishmania. 1701 62

Cytosolic NAD-dependent glyceraldehyde 3-P dehydrogenase (GAPDH; GapC; EC 1.2.1.12) catalyzes the oxidation of triose phosphates during glycolysis in all organisms, but additional functions of the protein has been put forward. Because of its reactive cysteine residue in the active site, it is susceptible to protein modification and oxidation. The addition of GSSG, and much more efficiently of S-nitrosoglutathione, was shown to inactivate the enzymes from Arabidopsis thaliana (isoforms GapC1 and 2), spinach, yeast and rabbit muscle. Inactivation was fully or at least partially reversible upon addition of DTT. The incorporation of glutathione upon formation of a mixed disulfide could be shown using biotinylated glutathione ethyl ester. Furthermore, using the biotin-switch assay, nitrosylated thiol groups could be shown to occur after treatment with nitric oxide donors. Using mass spectrometry and mutant proteins with one cysteine lacking, both cysteines (Cys-155 and Cys-159) were found to occur as glutathionylated and as nitrosylated forms. In preliminary experiments, it was shown that both GapC1 and GapC2 can bind to a partial gene sequence of the NADP-dependent malate dehydrogenase (EC 1.2.1.37; At5g58330). Transiently expressed GapC-green fluorescent protein fusion proteins were localized to the nucleus in A. thaliana protoplasts. As nuclear localization and DNA binding of GAPDH had been shown in numerous systems to occur upon stress, we assume that such mechanism might be part of the signaling pathway to induce increased malate-valve capacity and possibly other protective systems upon overreduction and initial formation of reactive oxygen and nitrogen species as well as to decrease and protect metabolism at the same time by modification of essential cysteine residues.
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PMID:Regulation of plant cytosolic glyceraldehyde 3-phosphate dehydrogenase isoforms by thiol modifications. 1829 9

Heterologous expression of Vitreoscilla hemoglobin (VHb) has been reported to improve cell growth, protein synthesis, metabolite productivity and nitric oxide detoxification. Although it has been proposed that such phenomenon is attributed to the enhancement of respiration and energy metabolism by facilitating oxygen delivery, the mechanism of VHb action remains to be elucidated. In the present study, changes of protein expression profile in Escherichia coli as a consequence of VHb production was investigated by two-dimensional gel electrophoresis (2-DE) in conjunction with peptide mass fingerprinting. Total protein extracts derived from cells expressing native green fluorescent protein (GFPuv) and chimeric VHbGFPuv grown in Luria-Bertani broth were prepared by sonic disintegration. One hundred microgram of proteins was individually electrophoresed in IEF-agarose rod gels followed by gradient SDS-PAGE gels. Protein spots were excised from the gels, digested to peptide fragments by trypsin, and analyzed using matrix-assisted laser desorption ionization-time of flight (MALDI-TOF) mass spectrometry. Results revealed that expression of VHbGFPuv caused an entire disappearance of tryptophanase as well as down-regulated proteins involved in various metabolic pathways, e.g. glycerol kinase, isocitrate dehydrogenase, aldehyde dehydrogenase, and D-glucose-D-galactose binding protein. Phenotypic assay of cellular indole production confirmed the differentially expressed tryptophanase enzymes in which cells expressing chimeric VHbGFP demonstrated a complete indole-negative reaction. Supplementation of delta-aminolevulinic acid (ALA) to the culture medium enhanced expression of glyceraldehyde-3-phosphate dehydrogenase and glycerol kinase. Our findings herein shed light on the functional roles of VHb on cellular carbon and nitrogen consumptions as well as regulation of other metabolic pathway intermediates, possibly by autoregulation of the catabolite repressor regulons.
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PMID:Shedding light on the role of Vitreoscilla hemoglobin on cellular catabolic regulation by proteomic analysis. 1834 84


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