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:3.6.1.3 (ATPase)
65,361 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Lead interferes with cellular energy metabolism by inhibiting ATP (Adenosine triphosphate) synthesis and hydrolysis. This study was conducted to determine in vitro effects of lead on Na+, K+-ATPase activity in four regions of adult rat brain: the cerebellum, the hippocampus, the frontal cortex and the brain stem. Male rats (Wistar strain) weighing 125-150 g were sacrificed, whole brain excised and the four regions were isolated. Each tissue was homogenized separately in sucrose (0.25 M) and imidazole (10 mM) buffer (pH 7.5) and P2 fraction was prepared by following established methods. The activity of ATPase was determined by measuring inorganic phosphate (Pi) liberated from ATP hydrolysis. The delineation of Na+, K+-activated component of ATPase was obtained by the difference between total ATPase and Mg2+-ATPase using 1 mM ouabain. The P2 fraction was incubated with 0, 5, 10, 25, 50 and 100 microM of lead at 37 degrees C for 10 min. The enzyme activity was expressed as micromoles of Pi liberated/mg protein/hr. The results indicated a concentration-dependent and region-specific response to lead. In vitro lead at 50 and 100 microM significantly inhibited ATPase activity in all regions of the brain. It was also observed that in the control rats, the enzyme activity was high in cerebellum and hippocampus regions of the brain. In vitro dithiothreitol (DTT) protected the enzyme activity from IC50 lead in four regions of brain. In cerebellum and hippocampus, a 5 microM DTT provided 100% protection against IC50 lead. These results suggest that lead interferes with the ion transport mechanism and cellular energy metabolism of the brain and this effect is region specific.
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PMID:In vitro effect of lead on Na+, K+-ATPase activity in different regions of adult rat brain. 1281 96

Lead phosphate deposition technique was used to investigate the changes and characteristic distribution of ATPase activity in the paranodules of tabacoo. We found that ATPase activity was closely associated with cell type and cell developmental state, thus it was different in various cells and rhizobia. No lead phosphate granules were located in the menstematic cells, although there were a small number of lead phosphate granules in the cytoplasm and organelles of the cells without rhizobia, they did not exist in the young and mature rhizobia. On the contrary, upon the senscence of the cells and rhizobia, a large number of lead phosphate granules appeared on the plasmalemmas and in the cell walls and the inside surfaces of the rhizobia. When the cells and rhizobia progressively senesced, lead phosphate granules increased in number, and they were widely distributed on the tonoplasts, plasmalemmas, cell walls, intercellular layers and in the intercellular spaces. At the same time, they also appeared on the surfaces and in the cytoplasm and nucleoids of the rhizobia. Due to cell disintegration, lead phosphategranules obviously decreased in number, they were only located on the plasmalemmas and membrane-vesicular structures which came from disintegrated organelles.
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PMID:[Changes and distribution of ATPase activity in the paranodules of Nicotiana tabacum]. 1457 95

P1B-type ATPases transport a variety of metals (Cd2+, Zn2+, Pb2+, Co2+, Cu2+, Ag+, Cu+) across biomembranes. Characteristic sequences CP[C/H/S] in transmembrane fragment H6 were observed in the putative transporting metal site of the founding members of this subfamily (initially named CPx-ATPases). In spite of their importance for metal homeostasis and biotolerance, their mechanisms of ion selectivity are not understood. Studies of better-characterized P(II)-type ATPases (Ca-ATPase and Na,K-ATPase) have identified three transmembrane segments that participate in ion binding and transport. Testing the hypothesis that metal specificity is determined by conserved amino acids located in the equivalent transmembrane segments of P1B-type ATPases (H6, H7, and H8), 234 P1B-ATPase protein sequences were analyzed. This showed that although H6 contains characteristic CPX or XPC sequences, conserved amino acids in H7 and H8 provide signature sequences that predict the metal selectivity in each of five P1B-ATPase subgroups identified. These invariant amino acids contain diverse side chains (thiol, hydroxyl, carbonyl, amide, imidazolium) that can participate in transient metal coordination during transport and consequently determine the particular metal selectivity of each enzyme. Each subgroup shares additional structural characteristics such as the presence (or absence) of particular amino-terminal metal-binding domains and the number of putative transmembrane segments. These differences suggest unique functional characteristics for each subgroup in addition to their particular metal specificity.
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PMID:Identification of ion-selectivity determinants in heavy-metal transport P1B-type ATPases. 1469 49

The mechanism of branchial lead uptake and interplay with Ca(2+) transport was investigated in the freshwater rainbow trout Oncorhynchus mykiss. Lead significantly reduced Ca(2+) influx by approximately 40% and 30% after exposure to 2.3+/-0.1 and 1.4+/-0.2 micromol l(-1) dissolved lead, respectively, for 0-48 h. Acute inhibition of Ca(2+) influx by lead exhibited typical Michaelis-Menten kinetics with an approximate 16-fold increase in K(m), whereas J(max) values did not significantly change, yielding an inhibitor constant (K(i,Pb)) of 0.48 micromol l(-1). Alternative analyses suggest the possibility of a mixed competitive/non-competitive interaction at the highest lead concentration tested (4.8 micromol l(-1)). Branchial lead accumulation was reduced with increasing waterborne Ca(2+) concentrations, suggesting a protective effect of Ca(2+) against lead uptake at the gill. The apical entries of Ca(2+) and lead were both inhibited (55% and 77%, respectively) by the addition of lanthanum (1 micromol l(-1)) to the exposure water. The use of cadmium (1 micromol l(-1)) and zinc (100 micromol l(-1)) as voltage-independent calcium channel competitors also reduced branchial lead uptake by approximately 56% and 47%, respectively. Nifedipine and verapamil (up to 100 micromol l(-1)), both voltage-dependent calcium channel blockers, had no effect on gill lead accumulation. CaCl(2) injection reduced both Ca(2+) and lead uptake by the gills. This suggests transport of lead through apical voltage-independent calcium channels, similar to the entry of Ca(2+). High-affinity Ca(2+)-ATPase activity was not acutely affected by lead, but a significant 80% reduction in activity occurred during exposure for 96 h to 5.5+/-0.4 micromol l(-1) dissolved lead, indicating a possible non-competitive component to lead-induced Ca(2+) disruption. The effect of lead on Ca(2+) efflux was investigated and found to be insignificant. We conclude that uptake of lead occurs, at least in part, by the same mechanism as Ca(2+), which results in disruption of Ca(2+) influx and ultimately Ca(2+) homeostasis.
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PMID:Characterization of branchial lead-calcium interaction in the freshwater rainbow trout Oncorhynchus mykiss. 1474 13

In this study, we characterized lead (Pb2+) accumulation and storage by the aquatic fern Azolla filiculoides. Lead precipitates were detected in the vacuoles of mesophyll cells of Azolla plants cultured for 6 d in rich growth medium containing 20 mg l(-1) Pb2+. Energy dispersive spectroscopy (EDS) analysis of the relative element content of leaves collected from these plants revealed a 100% increase in the levels of P, S, Na and Ca and a 40% decrease in Mg and Cl compared to the untreated plants. Both Azolla whole plants and isolated apoplasts were incubated for 6 d in 20 mg l(-1) Pb2+. Lead content in the whole plant composed 0.37%, 2.3% and 1.8% of the dry weight after 2, 4 and 6 d of growth, respectively, while the isolated Azolla apoplast contained 0.125%, 1.22% and 1.4% Pb2+, respectively. Lead content in Azolla whole plant increase by 200%, 100% and 22% after 2, 4 and 6 d of growth, respectively, when compared to Azolla apoplast. Dark, electron dense deposits of lead were observed in light and transmission electron microscope in leaf cells treated with lead. All the observed lead deposits were localized in vacuoles while larger lead deposits were found in mature leaves than in young leaves. No lead deposits were found in cells of the cyanobiont Anabaena when the plants were exposed to similar conditions. Activity and content of V-H+-ATPase were studied in Azolla plants grown in the presence of 20, 40 and 80 mg l(-1) of lead for a period of 4 d. Activity of V-H+-ATPase was increased by 190%, 210% and 220%, respectively, but the content of V-H+-ATPase was reduced by all lead concentrations.
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PMID:Lead accumulation in the aquatic fern Azolla filiculoides. 1533 Oct 93

PIB-type ATPases transport heavy metal ions (Cu+, Cu2+, Zn2+, Cd2+, Co2+, etc.) across biological membranes. Several members of this subfamily are present in plants. Higher plants are the only eukaryotes where putative Zn(2+)-ATPases have been identified. We have cloned HMA2, a PIB-ATPase present in Arabidopsis (Arabidopsis thaliana), and functionally characterized this enzyme after heterologous expression in yeast (Saccharomyces cerevisiae). HMA2 is a Zn(2+)-dependent ATPase that is also activated by Cd2+ and, to a lesser extent, by other divalent heavy metals (Pb2+, Ni2+, Cu2+, and Co2+). The enzyme forms an acid-stable phosphorylated intermediate and is inhibited by vanadate. HMA2 interacts with Zn2+ and Cd2+ with high affinity (Zn2+ K(1/2) = 0.11 +/- 0.03 microm and Cd2+ K(1/2) = 0.031 +/- 0.007 microm). However, its activity is dependent on millimolar concentrations of Cys in the assay media. Zn2+ transport determinations indicate that the enzyme drives the outward transport of metals from the cell cytoplasm. Analysis of HMA2 mRNA suggests that the enzyme is present in all plant organs and transcript levels do not change in plants exposed to various metals. Removal of HMA2 full-length transcript results in Zn2+ accumulation in plant tissues. hma2 mutant plants also accumulate Cd2+ when exposed to this metal. These results suggest that HMA2 is responsible for Zn2+ efflux from the cells and therefore is required for maintaining low cytoplasmic Zn2+ levels and normal Zn2+ homeostasis.
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PMID:Arabidopsis HMA2, a divalent heavy metal-transporting P(IB)-type ATPase, is involved in cytoplasmic Zn2+ homeostasis. 1547 10

Lead (Pb), depositing primarily in astroglia in the brain, is a well-known neurotoxicant and a risk factor for neurologic disorders. Pb has been reported to induce oxidative stress by probably the disturbance of copper (Cu) homeostasis in astroglia. Thus, we hypothesized that Pb-induced oxidative stress is initiated by interfering with Cu transporter in astroglia. In this study, we observed Pb-induced oxidative stress as indicated by reactive oxygen species (ROS) augmentation and GRP78 and GRP94 protein induction, and it was parallel to Cu accumulation intracellularly by Pb. To further address Cu transporter as a potential Pb target, a heavy metal-binding (HMB) domain of Cu-transporting ATPase (Atp7a) was overexpressed and purified. Evidence showed that one molecule of HMB chelated 11 Pb ions or seven Cu ions and that Pb competed with Cu for binding to HMB. These findings suggest that Pb-induced oxidative stress results from the impairment of Cu metabolism by Pb targeting of Atp7a.
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PMID:The involvement of copper transporter in lead-induced oxidative stress in astroglia. 1607 12

ZntA from Escherichia coli is a member of the P1B-type ATPase family that confers resistance specifically to Pb2+, Zn2+, and Cd2 salts by active efflux across the cytoplasmic membrane. P1B-type ATPases are important for homeostasis of metal ions such as Cu+, Ag+, Pb2+, Zn2+, Cd2+ Cu2+, and Co2+, with different subgroups showing specificity for different metal ions. Sequence alignments of P1B-type ATPases show that ZntA and close homologues have a strictly conserved Asp714 in the eighth transmembrane domain that is not conserved in other subgroups of P1B-type ATPases. However, in the sarcoplasmic reticulum Ca2+-ATPase, a structurally characterized P-type ATPase, the residue corresponding to Asp714 is a metal-binding residue. Four site-specific mutants at Asp714, D714E, D714H, D714A, and D714P, were characterized. A comparison of their metal-binding affinity with that of wtZntA revealed that Asp714 is a ligand for the metal ion in the transmembrane site. Thus, Asp714 is one of the residues that determine metal ion specificity in ZntA homologues. All four substitutions at Asp714 in ZntA resulted in complete loss of in vivo resistance activity and complete or large reductions in ATPase activity, though D714E and D714H retained the ability to bind metal ions with high affinity at the transmembrane site. Thus, the ability to bind metal ions with high affinity did not correlate with high activity. The metal-binding affinity of the N-terminal site remained unchanged in all four mutants. The affinities of the two metal-binding sites in wtZntA determined in this study are similar to values reported previously for the individual sites in isolated ZntA fragments.
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PMID:Conserved aspartic acid 714 in transmembrane segment 8 of the ZntA subgroup of P1B-type ATPases is a metal-binding residue. 1666 35

Lead is one of the industrially important heavy metals that causes male reproductive impairment among battery and paint factory workers, but information on the structure-function integrity of human spermatozoa is still limited. Therefore, it was necessary to investigate the effect of lead on sperm structure and functional activity in these workers. Oligozoospermia with concomitant lowering of sperm protein and nucleic acid content and the percentage of sperm DNA hyploidy (P <0.001) suggested the diminution of sperm cell production after occupational lead exposure. Low sperm vitality and hypoosmotic swelling percentage along with high malondialdehyde content and altered seminal plasma ascorbate level (P<0.001) indicating damage of sperm cell surface, might be due to high membrane lipid peroxidation and failure of non-enzymatic antioxidant protection after lead exposure. Alteration of sperm membrane surface was also evidenced from scanning electron microscopy and further authenticated by atomic and lateral force microscopy. Lowering of sperm velocity, gross and forward progressive motility with high stationary motile spermatozoa (P<0.001) suggested retarded sperm activity among the exposed workers, which was supported by high seminal plasma fructose level and reduced activity of sperm ATPase (P < 0.001). Increased incidence of teratozoospermia was also associated with high blood and semen lead level (PbB, PbS) (P<0.001). Therefore, the results suggested that lead not only affects the sperm count, but also damages the sperm structure and membrane integrity, motility and functional activity among the battery and paint factory workers.
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PMID:Inorganic lead exposure in battery and paint factory: effect on human sperm structure and functional activity. 1678 Feb 24

P(1B)-type ATPases transport heavy metals (Cu+, Cu2+, Zn2+, Co2+, Cd2+, Pb2+) across membranes. Present in most organisms, they are key elements for metal homeostasis. P(1B)-type ATPases contain 6-8 transmembrane fragments carrying signature sequences in segments flanking the large ATP binding cytoplasmic loop. These sequences made possible the differentiation of at least four P(1B)-ATPase subgroups with distinct metal selectivity: P(1B-1): Cu+, P(1B-2): Zn2+, P(1B-3): Cu2+, P(1B-4): Co2+. Mutagenesis of the invariant transmembrane Cys in H6, Asn and Tyr in H7 and Met and Ser in H8 of the Archaeoglobus fulgidus Cu+-ATPase has revealed that their side chains likely coordinate the metals during transport and constitute a central unique component of these enzymes. The structure of various cytoplasmic domains has been solved. The overall structure of those involved in enzyme phosphorylation (P-domain), nucleotide binding (N-domain) and energy transduction (A-domain), appears similar to those described for the SERCA Ca2+-ATPase. However, they show different features likely associated with singular functions of these proteins. Many P(1B)-type ATPases, but not all of them, also contain a diverse arrangement of cytoplasmic metal binding domains (MBDs). In spite of their structural differences, all N- and C-terminal MBDs appear to control the enzyme turnover rate without affecting metal binding to transmembrane transport sites. In addition, eukaryotic Cu+-ATPases have multiple N-MBD regions that participate in the metal dependent targeting and localization of these proteins. The current knowledge of structure-function relationships among the different P(1B)-ATPases allows for a description of selectivity, regulation and transport mechanisms. Moreover, it provides a framework to understand mutations in human Cu+-ATPases (ATP7A and ATP7B) that lead to Menkes and Wilson diseases.
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PMID:The structure and function of heavy metal transport P1B-ATPases. 1721 55


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