Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.6.3.14 (ATP synthase)
 7,042 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

31P nuclear magnetic resonance (NMR) saturation-transfer (ST) techniques have been used to measure steady-state flows through phosphate-adenosine 5'-triphosphate (ATP) exchange reactions in glucose-grown derepressed yeast. Our results have revealed that the reactions catalyzed by glyceraldehyde-3-phosphate dehydrogenase/phosphoglycerate kinase (GAPDH/PGK) and by the mitochondrial ATPase contribute to the observed ST. Contributions from these reactions were evaluated by performing ST studies under various metabolic conditions in the presence and absence of either iodoacetate, a specific inhibitor of GAPDH, or the respiratory chain inhibitor antimycin A. Intracellular phosphate (Pi) longitudinal relaxation times were determined by performing inversion recovery experiments during steady-state ATP gamma saturation and were used in combination with ST data to determine Pi consumption rates. 13C NMR and O2 electrode measurements were also conducted to monitor changes in rates of glucose consumption and O2 consumption, respectively, under the various metabolic conditions examined. Our results suggest that GAPDH/PGK-catalyzed Pi-ATP exchange is responsible for antimycin-resistant saturation transfer observed in anaerobic and aerobic glucose-fed yeast. Kinetics through GAPDH/PGK were found to depend on metabolic conditions. The coupled system appears to operate in a unidirectional manner during anaerobic glucose metabolism and bidirectionally when the cells are respiring on exogenously supplied ethanol. Additionally, mitochondrial ATPase activity appears to be responsible for the transfer observed in iodoacetate-treated aerobic cells supplied with either glucose or ethanol, with synthesis of ATP occurring unidirectionally.
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PMID:31P NMR saturation-transfer measurements in Saccharomyces cerevisiae: characterization of phosphate exchange reactions by iodoacetate and antimycin A inhibition. 332

Recent 31P-NMR saturation transfer measurements of flux between Pi and ATP in the perfused rat heart (Kingsley-Hickman, P., Sako, E.Y., Andreone, P.A., St. Cyr, J.A., Michurski, S., Foker, J.E., From, A.H.L., Petein, M. and Ugurbil, K. (1986) FEBS Lett. 198, 159-163) have given a P/O ratio (mols ATP synthesised/atoms oxygen consumed) which was close to 6. This anomalously high value was attributed to exchange in the reaction catalysed by the mitochondrial F1F0-ATP synthase. We show here that this exchange could also be catalysed by the glycolytic enzymes glyceraldehyde-3-phosphate dehydrogenase and phosphoglycerate kinase. 31P-NMR saturation transfer measurements of the exchange catalysed by these enzymes in vitro, under conditions designed to mimic those present in the perfused rat heart, have shown that they could catalyse a quantitatively significant Pi-ATP exchange in vivo. A three-site exchange model is used to investigate the effects of Pi-ATP exchange on saturation transfer measurements of the reverse flux in the creatine kinase reaction. A discrepancy in the measured and forward and reverse fluxes in this reaction has been attributed previously to the participation of the gamma-phosphate of ATP in other exchange reactions.
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PMID:31P-NMR saturation transfer measurements of exchange between Pi and ATP in the reactions catalysed by glyceraldehyde-3-phosphate dehydrogenase and phosphoglycerate kinase in vitro. 382 1

Cytokinins induce two specific morphological alterations in mosses: (i) the differentiation of a tip-growing cell into a three-faced apical cell (the so-called bud), and (ii) the division of chloroplasts. In a developmental mutant of the moss Physcomitrella patens (Hedw.) B.S.G. (mutant PC22) impeded in both cellular differentiation (bud production) and chloroplast division, addition of cytokinin (N6-delta 2-isopentenyladenine) led to bud production after 3 d in the wild type and after 7 d in the mutant. Hormone induced a division of the mutant macrochloroplasts starting within 24 h and ongoing for 72 h. During this period the abundances of several plastid proteins changed in both genotypes as judged by two-dimensional-protein gel electrophoresis, silver staining and subsequent quantification with novel computer software. Eight of these polypeptides were isolated independently, subjected to microsequencing and thus identified, resulting in the first protein sequence data from a moss. Three polypeptides (24 kDa, 22 kDa, 20 kDa) were found to be homologous to enhancer protein OEE2 of the oxygen-evolving complex, four to represent isoforms of phosphoglycerate kinase (EC 2.7.2.3), and one was identified as the beta-chain of chloroplast ATPase (EC 3.6.1.34). Possible involvement of these key enzymes of the chloroplast energy-conversion machinery in organelle division and in cellular differentiation is discussed. Further sequence information was obtained from both subunits of ribulose-1,5-bisphosphate carboxylase/oxygenase (EC 4.1.1.39). Amounts of these polypeptides were not appreciably affected by cytokinin in moss chloroplasts.
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PMID:Cytokinin affects nuclear- and plastome-encoded energy-converting plastid enzymes. 912 36

Glucose is the major source of brain energy and is essential for maintaining normal brain and neuronal function. Hypoglycemia causes impaired synaptic transmission. This occurs even before significant reduction in global cellular ATP concentration, and relationships among glycolysis, ATP supply, and synaptic transmission are not well understood. We demonstrate that the glycolytic enzymes glyceraldehyde phosphate dehydrogenase (GAPDH) and 3-phosphoglycerate kinase (3-PGK) are enriched in synaptic vesicles, forming a functional complex, and that synaptic vesicles are capable of accumulating the excitatory neurotransmitter glutamate by harnessing ATP produced by vesicle-bound GAPDH/3-PGK at the expense of their substrates. The GAPDH inhibitor iodoacetate suppressed GAPDH/3-PGK-dependent, but not exogenous ATP-dependent, [(3)H]glutamate uptake into isolated synaptic vesicles. It also decreased vesicular [(3)H]glutamate content in the nerve ending preparation synaptosome; this decrease was reflected in reduction of depolarization-induced [(3)H]glutamate release. In contrast, oligomycin, a mitochondrial ATP synthase inhibitor, had minimal effect on any of these parameters. ADP at concentrations above 0.1 mm inhibited vesicular glutamate and dissipated membrane potential. This suggests that the coupled GAPDH/3-PGK system, which converts ADP to ATP, ensures maximal glutamate accumulation into presynaptic vesicles. Together, these observations provide insight into the essential nature of glycolysis in sustaining normal synaptic transmission.
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PMID:Glycolysis and glutamate accumulation into synaptic vesicles. Role of glyceraldehyde phosphate dehydrogenase and 3-phosphoglycerate kinase. 1248 40

The plastids of red algae, green plants, and glaucophytes may have originated directly from a cyanobacterium-like prokaryote via primary endosymbiosis. In contrast, the plastids of other lineages of eukaryotic phototrophs appear to be the result of secondary or tertiary endosymbiotic events involving a phototrophic eukaryote and a eukaryotic host cell. Although phylogenetic analyses of multiple plastid genes from a wide range of eukaryotic lineages have been carried out, the phylogenetic positions of the secondary plastids of the Chromista (Heterokontophyta, Haptophyta and Cryptophyta) are ambiguous in a range of different analyses. This ambiguity may be the result of unusual substitutions or bias in the plastid genes established by the secondary endosymbiosis. In this study, we carried out phylogenetic analyses of five nuclear genes of cyanobacterial origin (6-phosphogluconate dehydrogenase [gnd], oxygen-evolving-enhancer [psbO], phosphoglycerate kinase [pgk], delta-aminolevulinic acid dehydratase [aladh], and ATP synthase gamma [atpC] genes), using the genome sequence data from the primitive red alga Cyanidioschyzon merolae 10D. The sequence data robustly resolved the origin of the cyanobacterial genes in the nuclei of the Chromista (Heterokontophyta and Haptophyta) and Dinophyta, before the divergence of the extant red algae (including Porphyra [Rhodophyceae] and Cyanidioschyzon [Cyadidiophyceae]). Although it is likely that gnd genes in the Chromista were transmitted from the cyanobacterium-like ancestor of plastids in the primary endosymbiosis, other genes might have been transferred from nuclei of a red algal ancestor in the secondary endosymbiosis. Therefore, the results indicate that the Chromista might have originated from the ancient secondary endosymbiosis before the divergence of extant red algae.
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PMID:Cyanobacterial genes transmitted to the nucleus before divergence of red algae in the Chromista. 1538 13

In most flowering plants, the female gametophyte develops in an ovule deeply embedded in the ovary. Through double fertilization, the egg cell fuses with the sperm cell, resulting in a zygote, which develops into the embryo. In the present study, we analyzed egg cell lysates by polyacrylamide gel electrophoresis and subsequent mass spectrometry-based proteomics technology, and identified major protein components expressed in the egg cell. The identified proteins included three cytosolic enzymes of the glycolytic pathway, glyceraldehyde-3-phosphate dehydrogenase, 3-phosphoglycerate kinase and triosephosphate isomerase, two mitochondrial proteins, the ATP synthase beta-subunit and an adenine nucleotide transporter, and annexin p35. In addition, expression levels of these proteins in the egg cell were compared with those in the early embryo, the central cell and the suspension cell. Annexin p35 was highly expressed only in the egg cell, and glyceraldehyde-3-phosphate dehydrogenase, 3-phosphoglycerate kinase and the adenine nucleotide transporter were expressed at higher levels in egg cells than in central and cultured cells. These results indicate that annexin p35 in the egg cell and zygote is involved in the exocytosis of cell wall materials, which is induced by a fertilization-triggered increase in cytosolic Ca2+ levels, and that the egg cell is rich in an enzyme subset for the energy metabolism.
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PMID:Identification of major proteins in maize egg cells. 1556 24

Anthrax toxin produced by Bacillus anthracis is a tripartite toxin comprising of protective antigen (PA), lethal factor (LF) and edema factor (EF). PA is the receptor-binding component, which facilitates the entry of LF or EF into the cytosol. EF is a calmodulin-dependent adenylate cyclase that causes edema whereas LF is a zinc metalloprotease and leads to necrosis of macrophages. It is also important to note that the exact mechanism of LF action is still unclear. With this view in mind, in the present study, we investigated a proteome wide effect of anthrax lethal toxin (LT) on mouse macrophage cells (J774A.1). Proteome analysis of LT-treated and control macrophages revealed 41 differentially expressed protein spots, among which phosphoglycerate kinase I, enolase I, ATP synthase (beta subunit), tubulin beta2, gamma-actin, Hsp70, 14-3-3 zeta protein and tyrosine/tryptophan-3-monooxygenase were found to be down-regulated, while T-complex protein-1, vimentin, ERp29 and GRP78 were found to be up-regulated in the LT-treated macrophages. Analysis of up- and down-regulated proteins revealed that primarily the stress response and energy generation proteins play an important role in the LT-mediated macrophage cell death.
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PMID:Proteome analysis of mouse macrophages treated with anthrax lethal toxin. 1569 49

We found that appropriate treatment with a highly potent and long-lasting abscisic acid analog enhanced the tissue expansion of scutellum during early seedling development of rice, accompanied by increases of protein and starch accumulation in the tissue. A comparative display of the protein expression patterns in the abscisic acid analog-treated and non-treated tissues on two dimensional gel electrophoretogram indicated that approximately 30% of the scutellar proteins were induced by abscisic acid. The abscisic acid-induced proteins included sucrose metabolizing, glycolytic, and ATP-producing enzymes. Most of these enzyme proteins also increased during the seedling growth. In addition, the expression of some isoforms of UDP-glucose pyrophosphorylase, 3-phosphoglycerate kinase, and mitochondrial ATP synthase beta chain was stimulated in the scutellum, with suppressed expression of alpha-amylase. We concluded that abscisic acid directly and indirectly stimulates the expression of numerous proteins, including carbohydrate metabolic enzymes, in scutellar tissues.
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PMID:Proteomic characterization of tissue expansion of rice scutellum stimulated by abscisic acid. 1748 61

Iron accumulation has been associated with several pathological conditions such as Friedreich ataxia. This human disorder is caused by decreased expression of frataxin. Iron-overload triggers oxidative stress, but the main targets of such stress are not known. In yeast cells lacking the frataxin ortholog YFH1, we have identified a set of 14 carbonylated proteins, which include mitochondrial ATP synthase, phosphoglycerate kinase, pyruvate kinase, and molecular chaperones. Interestingly, most of the target proteins are magnesium- and/or nucleotide-binding proteins. This key feature leads us to postulate that when iron accumulates, chelatable iron replaces magnesium at the corresponding metal-binding site, promoting selective damage to these proteins. Consistent with this hypothesis, in vitro experiments performed with pure pyruvate kinase and phosphoglycerate kinase showed that oxidation of these proteins can be prevented by magnesium and increased by the presence of ATP. Also, chelatable iron, which forms complexes with nucleotides, showed a sevenfold increase in Deltayfh1 cells. Moreover, lowering chelatable iron in Deltayfh1 cells by desferrioxamine prevented enzyme inactivation. As a general conclusion, we propose that magnesium bound to proteins is replaced by chelatable iron when this metal accumulates. This mechanism explains selective protein oxidation and provides clues for better understanding of iron-overloading pathologies.
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PMID:Major targets of iron-induced protein oxidative damage in frataxin-deficient yeasts are magnesium-binding proteins. 1828 Feb 58

Numerous investigations point to the importance of oxidative imbalance in mediating AD pathogenesis. Accumulated evidence indicates that lipid peroxidation is an early event during the evolution of the disease and occurs in patients with mild cognitive impairment (MCI). Because MCI represents a condition of increased risk for Alzheimer's disease (AD), early detection of disease markers is under investigation. Previously we showed that HNE-modified proteins, markers of lipid peroxidation, are elevated in MCI hippocampus and inferior parietal lobule compared to controls. Using a redox proteomic approach, we now report the identity of 11 HNE-modified proteins that had significantly elevated HNE levels in MCI patients compared with controls that span both brain regions: Neuropolypeptide h3, carbonyl reductase (NADPH), alpha-enolase, lactate dehydrogenase B, phosphoglycerate kinase, heat shock protein 70, ATP synthase alpha chain, pyruvate kinase, actin, elongation factor Tu, and translation initiation factor alpha. The enzyme activities of lactate dehydrogenase, ATP synthase, and pyruvate kinase were decreased in MCI subjects compared with controls, suggesting a direct correlation between oxidative damage and impaired enzyme activity. We suggest that impairment of target proteins through the production of HNE adducts leads to protein dysfunction and eventually neuronal death, thus contributing to the biological events that may lead MCI patients to progress to AD.
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PMID:Redox proteomic identification of 4-hydroxy-2-nonenal-modified brain proteins in amnestic mild cognitive impairment: insight into the role of lipid peroxidation in the progression and pathogenesis of Alzheimer's disease. 1832 75


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