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:4.1.2.13 (aldolase)
3,461 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The nature of oxidative damage to Saccharomyces cerevisiae caused by levels of HOCl that inhibit cell replication was explored with the intent of identifying the loci of lethal lesions. Functions of cytosolic enzymes and organelles that are highly sensitive to inactivation by HOCl, including aldolase, glyceraldehyde-3-phosphate dehydrogenase (GAPDH), and the mitochondrion, were only marginally affected by exposure of the yeast to levels of HOCl that completely inhibited colony formation. Loss of function in membrane-localized proteins, including the hexose transporters and PMA1 H(+)-ATPase, which is the primary proton pump located within the S. cerevisiae plasma membrane, was also marginal and K(+) leak rates to the extracellular medium increased only slowly with exposure to increasing amounts of HOCl, indicating that the plasma membrane retained its intrinsic impermeability to ions and metabolites. Adenylate phosphorylation levels in fermenting yeast declined in parallel with viability; however, yeast grown on respiratory substrates maintained near-normal phosphorylation levels at HOCl doses several-fold greater than that required for killing. This overall pattern of cellular response to HOCl differs markedly from that previously reported for bacteria, which appear to be killed by inhibition of plasma membrane proteins involved in energy transduction. The absence of significant loss of function in critical oxidant-sensitive cellular components and retention of ATP-synthesizing capabilities in respiring yeast cells exposed to lethal levels of HOCl suggests that toxicity in this case may arise by programmed cell death.
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PMID:HOCl-mediated cell death and metabolic dysfunction in the yeast Saccharomyces cerevisiae. 1487 79

Vacuolar H+-ATPases (V-ATPases) are a family of ATP-driven proton pumps. They maintain pH gradients between intracellular compartments and are required for proton secretion out of the cytoplasm. Mechanisms of extrinsic control of V-ATPase are poorly understood. Previous studies showed that glucose is an important regulator of V-ATPase assembly in Saccharomyces cerevisiae. Human V-ATPase directly interacts with aldolase, providing a coupling mechanism for glucose metabolism and V-ATPase function. Here we show that glucose is a crucial regulator of V-ATPase in renal epithelial cells and that the effect of glucose is mediated by phosphatidylinositol 3-kinase (PI3K). Glucose stimulates V-ATPase-dependent acidification of the intracellular compartments in human proximal tubular cells HK-2 and porcine renal epithelial cells LLC-PK1. Glucose induces rapid ATP-independent assembly of the V1 and Vo domains of V-ATPase and extensive translocation of the V-ATPase V1 and Vo domains between different membrane pools and between membranes and the cytoplasm. In HK-2 cells, glucose stimulates polarized translocation of V-ATPase to the apical plasma membrane. The effects of glucose on V-ATPase trafficking and assembly can be abolished by pretreatment with the PI3K inhibitor LY294002 and can be reproduced in glucose-deprived cells by adenoviral expression of the constitutively active catalytic subunit p110alpha of PI3K. Taken together these data provide evidence that, in renal epithelial cells, glucose plays an important role in the control of V-ATPase-dependent acidification of intracellular compartments and V-ATPase assembly and trafficking and that the effects of glucose are mediated by PI3K-dependent signaling.
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PMID:Phosphatidylinositol 3-kinase-mediated effects of glucose on vacuolar H+-ATPase assembly, translocation, and acidification of intracellular compartments in renal epithelial cells. 1563 60

Fructose-bisphosphate aldolase is a glycolytic enzyme whose activity increases in rice roots treated with gibberellin (GA). To investigate the relationship between aldolase and root growth, GA-induced root aldolase was characterized. GA3 promoted an increase in aldolase accumulation when 0.1 microM GA3 was added exogenously to rice roots. Aldolase accumulated abundantly in roots, especially in the apical region. To examine the effect of aldolase function on root growth, transgenic rice plants expressing antisense aldolase were constructed. Root growth of aldolase-antisense transgenic rice was repressed compared with that of the vector control transgenic rice. Although aldolase activity increased by 25% in vector control rice roots treated with 0.1 microM GA3, FBPA activity increased very little by 0.1 microM GA3 treatment in the root of aldolase-antisense transgenic rice. Furthermore, aldolase co-immunoprecipitated with antibodies against vacuolar H+ -ATPase in rice roots. In the root of OsCDPK13-antisense transgenic rice, aldolase did not accumulate even after treatment with GA3. These results suggest that the activation of glycolytic pathway function accelerates root growth and that GA3-induced root aldolase may be modulated through OsCDPK13. Aldolase physically associates with vacuolar H-ATPase in roots and may regulate the vacuolar H-ATPase mediated control of cell elongation that determines root length.
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PMID:Characterization of fructose-bisphosphate aldolase regulated by gibberellin in roots of rice seedling. 1582 84

The mechanism of charge propagation in "ion channel sensors" (ICSs) consisting of gold electrodes modified with a layer of charged proteins and highly charged redox-active marker ions in solution was investigated by electrochemical techniques, QCM and AFM. The study is based on seven proteins (concanavalin A, cytochrome c, glucose oxidase, lysozyme, thyroglobulin, catalase, aldolase, and EF1-ATPase) in combination with seven electroactive marker ions ([Fe(CN)6]3-, [Fe(CN)6]4-, [Ru(NH3)6]3+, mono-, di-, and trimeric viologens), as well as a series of suppressor and enhancer ions leading to the following general statements: (i) electrostatic binding of charged marker ions to the domains of the protein is a prerequisite for an electrochemical current and (ii) charge propagation through the layer consists of electron hopping along surface-confined marker ions into the pores between adsorbed proteins. It is further shown that (iii) marker ions and suppressor ions with identical charge compete for oppositely charged sites on the protein domain, (iv) electrostatically bound multilayers of marker or enhancer ions with alternating charge form on a charged protein domain, and (v) self-exchange and exergonic ET catalysis between adsorbed marker ions and marker ions in solution take place. In addition to fundamental insight into the mechanism of charge propagation, valuable information for the design, optimization, and tailoring of new biosensors based on the ICS concept is demonstrated by the current findings.
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PMID:Charge propagation in "ion channel sensors" based on protein-modified electrodes and redox marker ions. 1608 79

Kidneys are essential for acid-base homeostasis, especially when organisms cope with changes in acid or base dietary intake. Because collecting ducts constitute the final site for regulating urine acid-base balance, we undertook to identify the gene network involved in acid-base transport and regulation in the mouse outer medullary collecting duct (OMCD). For this purpose, we combined kidney functional studies and quantitative analysis of gene expression in OMCDs, by transcriptome and candidate gene approaches, during metabolic acidosis. Furthermore, to better delineate the set of genes concerned with acid-base disturbance, the OMCD transcriptome of acidotic mice was compared with that of both normal mice and mice undergoing an adaptative response through potassium depletion. Metabolic acidosis, achieved through an NH4Cl-supplemented diet for 3 days, not only induced acid secretion but also stimulated the aldosterone and vasopressin systems and triggered cell proliferation. Accordingly, metabolic acidosis increased the expression of genes involved in acid-base transport, sodium transport, water transport, and cell proliferation. In particular, >25 transcripts encoding proteins involved in urine acidification (subunits of H-ATPase, kidney anion exchanger, chloride channel Clcka, carbonic anhydrase-2, aldolase) were co-regulated during acidosis. These transcripts, which cooperate to achieve a similar function and are co-regulated during acidosis, constitute a functional unit that we propose to call a "regulon".
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PMID:Kidney collecting duct acid-base "regulon". 1686 73

Triclosan was found to be a potent inhibitor of the F(H+)-ATPase of the oral pathogen Streptococcus mutans and to increase proton permeabilities of intact cells. Moreover, it acted additively with weak-acid transmembrane proton carriers, such as fluoride or sorbate, to sensitize glycolysis to acid inhibition. Even at neutral pH, triclosan could inhibit glycolysis more directly as an irreversible inhibitor of the glycolytic enzymes pyruvate kinase, lactic dehydro genase, aldolase, and the phosphoenolpyruvate:sugar phosphotransferase system (PTS). Cell glycolysis in suspensions or biofilms was inhibited in a pH-dependent manner by triclosan at a concentration of about 0.1 mmol/L at pH 7, approximately the lethal concentration for S. mutans cells in suspensions. Cells in intact biofilms were almost as sensitive to triclosan inhibition of glycolysis as were cells in suspensions but were more resistant to killing. Targets for irreversible inhibition of glycolysis included the PTS and cytoplasmic enzymes, specifically pyruvate kinase, lactic dehydrogenase, and to a lesser extent, aldolase. General conclusions are that triclosan is a multi-target inhibitor for mutans streptococci, which lack a triclosan-sensitive FabI enoyl-ACP reductase, and that inhibition of glycolysis in dental plaque biofilms, in which triclosan is retained after initial or repeated exposure, would reduce cariogenicity.
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PMID:Triclosan inhibition of membrane enzymes and glycolysis of Streptococcus mutans in suspensions and biofilms. 1711 Sep 66

The effects of zinc on growing rats were characterized using the dietary zinc-deficient (ZD) and Zinc-overdose (ZO) models. Zinc deficiency had negative effects on the host final body weight and liver zinc content, whereas zinc overdose had positive effects. In order to identify the molecular changes in the liver responding to dietary zinc status, cDNA microarrays were used to analyze the expression pattern of 9753 genes in the livers of rats fed ZD and ZO diet for 6 wk, compared with zinc-adequate ZA. The mRNA levels for 62 genes were affected significantly by the ZD diet, whereas 66 gene transcriptions were markedly changed in the ZO diet. Those predominant gene products involved in nitrogen metabolism (glutaminase), carbohydrate metabolism (aldolase), lipid metabolism (stearoyl-CoA desaturase), growth (insulin-like growth factor-binding protein), transcription and translation (zinc-finger protein), immune (natural-killer cell), signal transduction (mitogen- activated protein kinase), and ion transportation (ATPase Na+/K+ transporting peptide) were clustered. In conclusion, a number of mammalian genes related to zinc in the liver were identified. The characterization of the genes and their products will allow a more comprehensive analysis of the role of zinc in metabolism. Furthermore, the mRNA identified could be useful in establishing the mechanisms of zinc in the pleiotropic metabolisms in vivo.
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PMID:Gene expression profiles analysis of the growing rat liver in response to different zinc status by cDNA microarray analysis. 1743 60

Vacuolar proton-translocating ATPases (V-ATPases) are a family of highly conserved proton pumps that couple hydrolysis of cytosolic ATP to proton transport out of the cytosol. Although V-ATPases are involved in a number of cellular processes, how the proton pumps are regulated under physiological conditions is not well understood. We have reported that the glycolytic enzyme aldolase mediates V-ATPase assembly and activity by physical association with the proton pump (Lu, M., Holliday, L. S., Zhang, L., Dunn, W. A., and Gluck, S. L. (2001) J. Biol. Chem. 276, 30407-30413 and Lu, M., Sautin, Y., Holliday, L. S., and Gluck, S. L. (2004) J. Biol. Chem. 279, 8732-8739). In this study, we generate aldolase mutants that lack binding to the B subunit of V-ATPase but retain normal catalytic activities. Functional analysis of the aldolase mutants shows that disruption of binding between aldolase and the B subunit of V-ATPase results in disassembly and malfunction of V-ATPase. In contrast, aldolase enzymatic activity is not required for V-ATPase assembly. Taken together, these findings strongly suggest an important role for physical association between aldolase and V-ATPase in the regulation of the proton pump.
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PMID:Physical interaction between aldolase and vacuolar H+-ATPase is essential for the assembly and activity of the proton pump. 1757 70

Alzheimer's disease (AD) is a neurodegenerative disorder characterized by progressive decline in multiple cognitive domains. Its pathological hallmarks include senile plaques and neurofibrillary tangles. Mild cognitive impairment (MCI) is the earliest detectable stage of AD with limited symptomology and no dementia. The yearly conversion rate of patients from MCI to AD is 10-15%, although conversion back to normal is possible in a small percentage. Early diagnosis of AD is important in an attempt to intervene or slow the advancement of the disease. Early AD (EAD) is a stage following MCI and characterized by full-blown dementia; however, information involving EAD is limited. Oxidative stress is well-established in MCI and AD, including protein oxidation. Protein nitration also is an important oxidative modification observed in MCI and AD, and proteomic analysis from our laboratory identified nitrated proteins in both MCI and AD. Therefore, in the current study, a proteomics approach was used to identify nitrated brain proteins in the inferior parietal lobule from four subjects with EAD. Eight proteins were found to be significantly nitrated in EAD: peroxiredoxin 2, triose phosphate isomerase, glutamate dehydrogenase, neuropolypeptide h3, phosphoglycerate mutase1, H(+)- transporting ATPase, alpha-enolase and fructose-1,6-bisphosphate aldolase. Many of these proteins are also nitrated in MCI and late-stage AD, making this study the first to our knowledge to link nitrated proteins in all stages of AD. These results are discussed in terms of potential involvement in the progression of this dementing disorder.
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PMID:Proteomic identification of nitrated brain proteins in early Alzheimer's disease inferior parietal lobule. 1875 37

To examine the role of the tonoplast in plant salt tolerance and identify proteins involved in the regulation of transporters for vacuolar Na(+) sequestration, we exploited a targeted quantitative proteomics approach. Two-dimensional differential in-gel electrophoresis analysis of free flow zonal electrophoresis separated tonoplast fractions from control, and salt-treated Mesembryanthemum crystallinum plants revealed the membrane association of glycolytic enzymes aldolase and enolase, along with subunits of the vacuolar H(+)-ATPase V-ATPase. Protein blot analysis confirmed coordinated salt regulation of these proteins, and chaotrope treatment indicated a strong tonoplast association. Reciprocal coimmunoprecipitation studies revealed that the glycolytic enzymes interacted with the V-ATPase subunit B VHA-B, and aldolase was shown to stimulate V-ATPase activity in vitro by increasing the affinity for ATP. To investigate a physiological role for this association, the Arabidopsis thaliana cytoplasmic enolase mutant, los2, was characterized. These plants were salt sensitive, and there was a specific reduction in enolase abundance in the tonoplast from salt-treated plants. Moreover, tonoplast isolated from mutant plants showed an impaired ability for aldolase stimulation of V-ATPase hydrolytic activity. The association of glycolytic proteins with the tonoplast may not only channel ATP to the V-ATPase, but also directly upregulate H(+)-pump activity.
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PMID:Quantitative proteomics of the tonoplast reveals a role for glycolytic enzymes in salt tolerance. 2002 41


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