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)

The effect of stannous chloride on bone metabolism was examined in weanling male rats given oral dose of 1.0 mg Sn/kg at 12-h intervals for 28 days. Tin administration produced progressive increase in tin content of the femoral diaphysis and epiphysis. Calcium content in the femoral epiphysis but not diaphysis was significantly decreased by tin administration for 28 days, while inorganic phosphorus contents in the femoral diaphysis and epiphysis were not changed significantly. Acid and alkaline phosphatase activities in the femoral diaphysis and epiphysis were markedly reduced by tin administration for 3 days, and significant decreases in the femoral epiphysis were also observed at 28 days. Meanwhile, ATPase and pyrophosphatase activities in the femoral diaphysis and epiphysis were not altered significantly by tin administration. From the present study, of mineral composition and its related enzyme activity, the decreases of acid and alkaline phosphatase activities in the femoral epiphysis were regarded as the biochemical manifestation of the toxic action of inorganic tin.
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PMID:Changes in mineral composition and its related enzyme activity in the femur of rats orally administered stannous chloride. 732 88

The plasma membrane ATPase on the human umbilical vein endothelial cell line (ECV304) was demonstrated to be an ecto-enzyme. Hydrolysis of ATP was measured by monitoring the appearance of inorganic phosphorus. Hydrolysis of extracellular ATP was insensitive to oligomycin, vanadate, ouabain and N-ethylmaleimide, compounds that inhibit the intracellular ion pumping ATPases. Beta-Glycerophosphate (1-10 mM) or p-nitrophenyl phosphate (1-10 mM) did not inhibit hydrolysis of ATP, ruling out the involvement of non-specific phosphatases. Enzyme activity in buffer that had previously been incubated with cells was < 7%, showing that the enzyme activity measured did not result from release of intracellular enzymes. Consistent with this, the cell preparations used were estimated to be > 95% intact as judged by release of cytosolic enzyme lactate dehydrogenase. The enzyme activity was Ca2-/Mg2- dependent. Gramicidin S (20 microM), suramin (100-300 microM), chlorpromazine (250 microM), trifluoperazine (50-250 microM), and thioridazine (100 microM) inhibited the hydrolysis of ATP (3 mM) by 45-80%. The percentage inhibition produced by these substances was not altered in the presence of a concentration of alpha, beta-methylene ADP (10 microM) which inhibited hydrolysis of AMP (3 mM) by 90%, suggesting that these compounds inhibit ecto-ATPase and/or ecto-ADPase. Measurements of absolute amounts of ATP released from various tissues, including the heart, have been hindered because ATP is rapidly and sequentially hydrolysed to adenosine. Identification of compounds that inhibit ATP degradation would prove to be useful to overcome this problem and would lead to the development of invaluable pharmacological tools in many other aspects of purine research.
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PMID:Inhibition of extracellular ATP degradation in endothelial cells. 763 50

1. Three experiments were carried out to determine the phosphorus (P) requirements of laying hens aged 34 to 58 weeks (experiment 1), 59 to 70 weeks (experiment 2) and 22 to 50 weeks (experiment 3) given diets containing wheat, sorghum and soyabean meals as the main ingredients. Dietary total P (Pt) varied between 3.2 and 7.3 g/kg (experiment 1), 3.2 and 4.6 g/kg (experiment 2) and 3.0 and 6.6 g/kg (experiment 3). Hens were housed at either 18 degrees or 30 degrees C (experiments 1 and 2) and uncontrolled temperature (experiment 3), and in experiment 2 diets were fed without or with a phytase supplement of 500 units/g. 2. Dietary Pt had no significant effect on production measures in any experiment. Increases in dietary Pt adversely influenced egg shell quality although uterine calcium (Ca), ATPase and carbonic anhydrase activities were unaffected. 3. A 3-d-feeding trial in experiment 1 gave maximum Pt retentions of 228 mg/d at 18 degrees C and 204 mg/d at 30 degrees C. These were obtained with diets containing, respectively, 4.6 and 6.0 g Pt/kg. 4. Plasma inorganic P (Pi) increased consistently with increases in dietary Pt at all temperatures but plasma total Ca, and tibia Ca and P, were unaffected. 5. The inclusion of the phytase supplement in diets containing 3.2 and 4.6 g Pt/kg had an adverse effect on egg production at both temperatures in experiment 2. 6. A dietary Pt concentration of 3.2 g/kg, providing a calculated 1.2 g available P (Pav)/kg, with a dietary phytase activity of less than 200 units/kg, satisfied the P requirements of the hens used in these studies. However, the data from experiment 3 suggest that the Pt requirement of some flocks fed on wheat-based diets may be lower than 3.2 g/kg.
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PMID:Phosphorus requirements of laying hens fed on wheat-based diets. 765 2

Skeletal muscle energetics can be studied noninvasively at rest, during exercise, and in recovery using phosphorus nuclear magnetic resonance (31P-NMR). In resting muscle, inorganic phosphate (P(i)) and total cellular phosphate concentration are regulated by Na(+)-dependent P(i) transport. Insulin was shown to stimulate P(i) uptake in G-8 muscle cells, in isolated rat soleus muscle, and in human muscle in vivo under conditions of hyperinsulinemic-euglycemic clamp. The relationship between plasma P(i) and intracellular muscle P(i) was examined in a group of patients with elevated plasma P(i) resulting from renal failure. The total creatine content of muscle cells is controlled by an active creatine uptake in which beta 2-receptor stimulation and the activity of the Na(+)-K(+)-ATPase play a significant role. Recovery after exercise is entirely oxidative; the rate of ATP synthesis is largely controlled by ADP, the concentration of which is determined by the creatine kinase equilibrium that includes the concentration of H+. At the onset of aerobic dynamic exercise, ATP is maintained largely by glycolysis, producing lactic acid, and by phosphocreatine breakdown. After vasodilation, ATP synthesis becomes predominantly oxidative. The above processes can be quantitatively evaluated by 31P-NMR.
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PMID:Control of energy metabolism during muscle contraction. 852 7

Maleic acid administration is known to produce the Fanconi syndrome, although the biochemical mechanism is incompletely understood. In this study the effect of a single injection of maleic acid (50 mg/kg body wt, i.v.) on the rat renal ATPases was examined. Maleic acid rapidly caused bicarbonaturia, natriuresis, and kaliuresis. When nephron segments were microdissected, there was an 81 +/- 2% reduction in proximal convoluted tubule (PCT) Na-K-ATPase activity (P < 0.005) and a 48 +/- 4% reduction in PCT H-ATPase activity (P < 0.01). Enzyme activity (Na-K-ATPase, H-ATPase, H-K-ATPase) in the medullary thick ascending limb of Henle's loop and distal nephron segments was normal. In vitro, maleic acid (1 and 10 mM) inhibited Na-K-ATPase in PCT, but it had no effect on H-ATPase in PCT. Prior phosphate infusion to maleic acid-treated rats attenuated urinary bicarbonate wastage by 50% (P < 0.05); activity of proximal tubule Na-K-ATPase and H-ATPase activities were partially protected as compared to the animals given maleic acid alone (P < 0.05). Renal cortical ATP levels were not altered at the concentration of maleic acid used in this study (that is, 50 mg/kg body wt), but higher doses of maleic acid (that is, 500 and 1000 mg/kg body wt) caused ATP levels to fall. Maleic acid did not affect cortical medullary total phosphate concentration, however, P32 turnover (1 and 24 hr) was altered by prior phosphate infusion. A protective effect of prior phosphate loading on the membrane bound Pi pool (insoluble) was seen while the cytosolic Pi pool (soluble) was not different from control. Thus, maleic acid-induced "Fanconi" syndrome likely results from both direct inhibition of proximal tubule Na-K-ATPase activity and membrane-bound phosphorus depletion. The former mechanism would reduce activity of the sodium-dependent transporters (that is, Na/H antiporter), while the latter would inhibit the electrogenic proton pump (H-ATPase). The combination of reduced proximal tubule Na-H exchange and H-ATPase activities would markedly inhibit bicarbonate reabsorption and result in the metabolic acidosis universally seen in the Fanconi syndrome.
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PMID:Insights into the biochemical mechanism of maleic acid-induced Fanconi syndrome. 854 11

X-linked adrenoleucodystrophy is a disorder occurring in different clinical forms, characterized by adrenal, gonadal and nervous system dysfunction. The basis of the illness is a derangement of the peroxisomal system necessary to oxidize very long-chain fatty acids that accumulate in various tissues. The diagnosis relies on clinical signs and symptoms and on biochemical findings. The six reported cases presented idiopathic adrenal insufficiency. We measured the lipid composition of red blood cell (RBC) ghosts of patients and control subjects. The distribution of phosphorus among phospholipid classes was unaffected; we could not demonstrate any differences between the fatty acid patterns of RBC membrane, either in total lipid extracts or in separated lipid classes. However, we found an increase in total lipid (both phospholipid and cholesterol), in membrane viscosity and in the Na+/K(+)-dependent ATPase. Therefore, we report four main findings on ghosts in adrenoleucodystrophy patients: (a) very long-chain fatty acids do not accumulate; (b) the lipid-protein ratio increases; (c) fluidity decreases; and (d) the activity of ATPase increases. The last finding is proposed as a possible biochemical marker of the illness. We conclude that adrenoleucodystrophy affects deeply RBC membranes.
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PMID:Red blood cell ghosts are affected by adrenoleucodystrophy. 891 66

The position in the acyl phosphate linkage of the phosphorylated intermediate of (Na+, K+)-ATPase that is cleaved by N-methylhydroxylamine was compared with that of the model compound acetylphosphate. The products of the cleavage of the phosphoenzyme by methylhydroxylamine were the active enzyme and a N-P compound, not the inhibited enzyme and inorganic phosphate. This means that the bond cleaved by methylhydroxylamine was the O-P bond, not the C-O bond. In contrast, methylhydroxylamine did not cleave the O-P bond of acetylphosphate in solution, at pH values from 0.3 to 7.0, whether or not the phosphoryl group formed a complex with magnesium. Acetylphosphate and hydroxylamine formed acetohydroxamic acid. Therefore, the state of the acyl phosphate bond in the native phosphoenzyme and in acetylphosphate in solution was different, and the difference was not due to different dissociation states of their phosphoryl groups or the binding of magnesium to the phosphoenzyme. Molecular orbital calculations for acetylphosphate revealed that the phosphorus atom charge is more positive than the carbon atom, irrespective of the dissociation state of the phosphoryl group. Similarly, the overlapping electron population of the O-P bond is always smaller than that of the C-O bond. Thus, the electronic structure of the acyl phosphate linkage of acetylphosphate under vacuum supports the results obtained with the native phosphoenzyme, rather than those obtained with acetylphosphate in solution. The linkage in the active site of the phosphorylated intermediate of (Na+,K+)-ATPase appeared to be equivalent to the non-hydrated state of the model compound acetylphosphate. The phosphoenzyme with bound ouabain, or without a tightly bound divalent cation was insensitive to methylhydroxylamine. The native phosphoenzyme of (Ca2+)-ATPase was not susceptible to methylhydroxylamine.
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PMID:Non-hydrated state of the acyl phosphate group in the phosphorylated intermediate of (Na+,K+)-ATPase. 934

The article presents data of research concerning levels of adenosine triphosphate (ATP), adenosine diphosphate (ADP), adenosine monophosphate (AMP), activity of Na, K- and Ca, Mg-dependent adenosine triphosphatases, glucose-6-phosphate dehydrogenase, concentrations of sodium, potassium, calcium, magnesium and phosphorus in workers contacting some chemicals (pseudocumene, durene, dioxane-1,4, pyromellitic dianhydride, etc.) at work. All examinees were divided into 3 groups in consideration with intensity of chemical exposure: group 1--workers free of the exposure, group 2--workers exposed to the chemicals 2-3 times a week, group 3--workers exposed to the chemicals constantly at work during 3-5 years. Healthy individuals having no occupational exposure to the chemicals formed a reference group. Members of the groups 2 and 3 demonstrated lower levels of ATP, potassium, magnesium, calcium, decreased activity of Ca, Mg-dependent adenosinetriphosphatase and higher levels of ADP, AMP, Na, P and increased activity of Na, K-dependent adenosinetriphosphatase and glucose-6-phosphate dehydrogenase.
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PMID:[Changes in biochemical parameters of erythrocytes in workers engaged in pyromellitic dianhydride production]. 982 85

Rhizobium tropici forms nitrogen-fixing nodules on the roots of the common bean (Phaseolus vulgaris). Like other legume-Rhizobium symbioses, the bean-R. tropici association is sensitive to the availability of phosphate (P(i)). To better understand phosphorus movement between the bacteroid and the host plant, P(i) transport was characterized in R. tropici. We observed two P(i) transport systems, a high-affinity system and a low-affinity system. To facilitate the study of these transport systems, a Tn5B22 transposon mutant lacking expression of the high-affinity transport system was isolated and used to characterize the low-affinity transport system in the absence of the high-affinity system. The K(m) and V(max) values for the low-affinity system were estimated to be 34 +/- 3 microM P(i) and 118 +/- 8 nmol of P(i) x min(-1) x mg (dry weight) of cells(-1), respectively, and the K(m) and V(max) values for the high-affinity system were 0.45 +/- 0.01 microM P(i) and 86 +/- 5 nmol of P(i) x min(-1) x mg (dry weight) of cells(-1), respectively. Both systems were inducible by P(i) starvation and were also shock sensitive, which indicated that there was a periplasmic binding-protein component. Neither transport system appeared to be sensitive to the proton motive force dissipator carbonyl cyanide m-chlorophenylhydrazone, but P(i) transport through both systems was eliminated by the ATPase inhibitor N,N'-dicyclohexylcarbodiimide; the P(i) transport rate was correlated with the intracellular ATP concentration. Also, P(i) movement through both systems appeared to be unidirectional, as no efflux or exchange was observed with either the wild-type strain or the mutant. These properties suggest that both P(i) transport systems are ABC type systems. Analysis of the transposon insertion site revealed that the interrupted gene exhibited a high level of homology with kdpE, which in several bacteria encodes a cytoplasmic response regulator that governs responses to low potassium contents and/or changes in medium osmolarity.
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PMID:Characterization of two inducible phosphate transport systems in Rhizobium tropici. 1061 97

Baculovirus phosphatase (BVP) is a member of the metazoan RNA triphosphatase enzyme family that includes the RNA triphosphatase component of the mRNA capping apparatus. BVP and other metazoan RNA triphosphatases belong to a superfamily of phosphatases that act via the formation and hydrolysis of a covalent cysteinyl-phosphate intermediate. Here we demonstrate the formation of a BVP phosphoenzyme upon reaction with [gamma-(32)P]ATP and identify the linkage as a thiophosphate based on its chemical lability. We surmise that the phosphate is linked to Cys(119) of BVP because replacement of Cys(119) by alanine or serine abrogates phosphoenzyme formation and phosphohydrolase activity. The catalytic cysteine is situated within a conserved phosphate-binding loop ((118)HCTHGINRTGY(128)). We show that all of the non-aliphatic side chains of the phosphate-binding loop are functionally important, insofar as mutants H118A, H121A, N124A, R125A, T126A, and Y128A were inactive in gamma phosphate hydrolysis and the T120A mutant was 7% as active as wild-type BVP. Structure-activity relationships at the essential positions of the phosphate-binding loop were elucidated by conservative substitutions. A conserved aspartic acid (Asp(60)) invoked as a candidate general acid catalyst was dispensable for phosphohydrolase activity and phosphoenzyme formation by BVP. We propose that the low pK(a) of the bridging oxygen of the beta phosphate leaving group circumvents a requirement for expulsion by a proton donor during attack by cysteine on the gamma phosphorus. In contrast, a conserved aspartic acid is essential for the phosphomonoesterase reactions catalyzed by protein phosphatases, where the serine or tyrosine leaving groups have a much higher pK(a) than does ADP.
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PMID:Mechanism of phosphoanhydride cleavage by baculovirus phosphatase. 1095 17


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