Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.6.1.3 (ATPase)
 65,361 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The progress of research in the Central Nervous System (CNS) had led to the consideration of neurons and glia as indissociable functional complexes. Neuron-glia interactions are essential for the maturation of the CNS. Glial cells release trophic factors for neurons (NGF) and neurons release trophic factors for glia (GGF). Furthermore, the latter provide a substrate for the migration of neurons and guidance of axons by mean of adhesion molecules. In adults, the interactions between neurons and glial cells serve to maintain homeostasis. Thus, the glial cells perform the restoration of the metabolic equilibrium overthrown by the transmission of the nerve impulse and provide the glucose required for neuronal activity. The nerve impulse provokes increases in the cellular space of CO2, K+, NH3 and neurotransmitters which must be taken up to allow neuronal activity to continue (in normal conditions). Astrocytes perform the uptake of the extracellular K+ by means of passive ionic channels, ionic voltage-dependent channels and a sodium-potassium-ATPase-dependent pump. The oligodendrocytes are involved in the metabolism of CO2 by converting CO2 into carbonic acid by means of carbonic anhydrase. Oligodendrocytes and astrocytes play a role in terminating neural transmission by the uptake of the amino acid neurotransmitters, such as GABA, glutamate and aspartate. The catabolism of glutamate to glutamine by means of glutamine synthetase allows both the conversion of an excitatory amino acid into a neutral amino acid (which can diffuse in the extracellular space without causing neural transmission) and the reduction of cerebral NH3 content.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:[Neuron-glia interactions]. 178 93

We prepared proton-transporting membrane vesicles from the avian osteoclast's ruffled membrane, a specialized region of the cell surface that acidifies the bone resorption space. We demonstrated a unique conductive Cl- permeability that is charge coupled to the vesicle H(+)-ATPase and is required for acidification. Ion replacement indicated an anion selectivity of Br- approximately Cl- greater than SO4(2-) greater than NO3- approximately SCN- in supporting acidification. The anion channel blocker 4,4'-diisothiocyanatostilbene-2,2'-disulfonic acid (10 microM) was a competitive inhibitor of acidification and raised the Michaelis constant for ATP of the proton pump approximately 11-fold in 120 mM KCl. Inhibition was reversed by valinomycin, which provides an alternate path for charge neutralization. The Cl- dependence of acidification was nonlinear and yielded a Hill coefficient of 3-4, showing that it is distinct from a linear Cl- dependence reported for acidification of renal cortical endosomes. The K+ ionophore valinomycin augmented H+ transport in K2SO4, and not in KCl. Dependence of Cl- transport on membrane potential was confirmed by direct measurement of 36Cl- transport. We uncoupled charge transport from proton transport with a large excess of ammonia, which had no effect on 36Cl- accumulation in vesicles, and by measuring 36Cl- accumulation in response to a membrane diffusion potential, produced with a [K+] gradient and valinomycin in the absence of ATP. These experiments demonstrate that the electrogenic proton pump of the osteoclast ruffled membrane is charge coupled to a passive Cl- permeability in the same membrane.
 ...
PMID:Passive chloride permeability charge coupled to H(+)-ATPase of avian osteoclast ruffled membrane. 182 26

Tetrammine cobalt(III) phosphate [Co(NH3)4PO4] inactivates Na+/K(+)-ATPase in the E2 conformational state, dependent on time and concentration, according to Eqn (1): Co(NH3)4PO4 + E2 Kd in equilibrium E2.Co(NH3)4PO4k2----E'2.Co(NH3)4PO4. The inactivation rate constant k2 for the formation of a stable E'2.Co(NH3)4PO4 at 37 degrees C was 0.057 min-1; the dissociation constant, Kd = 300 microM. The activation energy for the inactivation process was 149 kJ/mol. ATP and the uncleavable adenosine 5'-[beta, gamma-methylene]triphosphate competed with Co(NH3)4PO4 for its binding site with Ks = 0.41 mM and 5 mM, respectively. MgPO4 competed with Co(NH3)4PO4 linearly, with Ks = 50 microM, as did phosphate (Ks = 16 mM) and Mg2+ (Ks = 160 microM). It is concluded that the MgPO4 analogue binds to the MgPO4-binding subsite of the low-affinity ATP-binding site (of the E2 conformation). Also, Na+ (Ks = 860 microM) protected the enzyme against inactivation in a competitive manner. From the intersecting (slope and intercept linear) noncompetitive effect of Na+ against the inactivation by Co(NH3)4PO4, apparent affinities of K+ for the free enzyme of 41 microM, and for the E.Co(NH3)4PO4 complex of 720 microM, were calculated. Binding of Co(NH3)4PO4 to the enzyme inactivated Na+/K(+)-ATPase and K(+)-activated phosphatase, and, moreover, prevented the occlusion of 86Rb+; however, the activity of the Na(+)-ATPase, the phosphorylation capacity of the high-affinity ATP-binding site and the ATP/ADP-exchange reaction remained unchanged. With Co(NH3)432PO4 a binding capacity of 135 pmol unit enzyme was found. Phosphorylation and complete inactivation of the enzyme with Co(NH3)432PO4 or the 32P-labelled tetramminecobalt ATP ([gamma-32P]Co(NH3)4ATP) at the low-affinity ATP-binding site, allowed (independent of the purity of the Na+/K(+)-ATPase preparation) a further incorporation of radioactivity from 32P-labelled tetraaquachromium(III) ATP ([gamma-32P]CrATP) to the high-affinity ATP-binding site with unchanged phosphorylation capacity. However, inactivation and phosphorylation of Na+/K(+)-ATPase by [gamma-32P]CrATP prevented the binding of Co(NH3)4 32PO4 or [gamma-32P]Co(NH3)4ATP to the enzyme. [gamma-32P]CO(NH3)4ATP and Co(NH3)432PO4 are mutually exclusive. The data are consistent with the assumption of a cooperation of catalytic subunits within an (alpha,beta)2-diprotomer, which change their interactions during the Na+/K(+)-pumping process. Our findings seem not to support a symmetrical Repke and Stein model of enzyme action.
 ...
PMID:Phosphate binding and ATP-binding sites coexist in Na+/K(+)-transporting ATPase, as demonstrated by the inactivating MgPO4 complex analogue Co(NH3)4PO4. 184 80

We have described the overall process that is responsible for the efficient transfer of ammonium from its production site in the proximal tubule cells to the final urine. The mechanism depends on direct NH4+ transport at a number of sites. There appears to be a predominance of NH3 over NH4+ transport in net total ammonia transport only in the collecting ducts and possibly the descending limbs of Henle's loop. Several examples of physiologically important direct NH4+ transport in the kidney were described. First, coupled Na/NH4/2Cl transport across the apical membrane of the thick ascending limb of Henle's loop mediates secondary active transport of ammonium, which drives countercurrent multiplication of ammonium in the renal medulla. Second, part of the NH4+ uptake across the apical membrane of the thick ascending limb may occur as a result of penetration by NH4+ through apical K+ channels. It is unknown whether NH4+ penetrates K+ channels in other tubule segments. Third, NH4+ can be actively transported into cells by substitution of NH4+ for K+ on the Na-K-ATPase. This NH4+ transport process is likely to be rapid enough to be physiologically significant only in the inner medulla, where NH4+ concentrations are high enough to successfully compete with K+. Fourth, NH4+ penetrates the paracellular pathway in some nephron segments such as the proximal tubule and thick ascending limb. Simple passive diffusion of NH4+ via the paracellular pathway is thought to be physiologically important in the thick ascending limb where it contributes to net NH4+ absorption.
 ...
PMID:NH4+ transport in the kidney. 189 Aug 4

Strain F, a recently isolated ruminal bacterium, grew rapidly with glutamate or glutamine as an energy source in the presence but not the absence of Na. Monensin, a Na+/H+ antiporter, completely inhibited bacterial growth and significantly reduced ammonia production (85%), but 3,3',4',5-tetrachlorosalicylanide (a protonophore) and valinomycin had little effect on growth or ammonia production. Dicyclohexylcarbodiimide, a H(+)-ATPase, inhibitor had no effect. The kinetics of glutamate and glutamine transport were biphasic, showing unusually high rates at high substrate concentrations. On the basis of low substrate concentrations (less than 100 microM), the Km values for glutamate and glutamine were 4 and 11 microM, respectively. Strain F had separate carriers for glutamate and glutamine which could be driven by a chemical gradient of Na. An artificial delta psi was unable to drive transport even when Na was present. The glutamate carrier had a single binding site for Na with a Km of 21 mM; the glutamine carrier appeared to have more than one binding site, and the Km was 2.8 mM. Neither carrier could use Li instead of Na. Histidine and serine were also rapidly transported by Na-dependent systems, but serine alone did not allow growth even when Na was present. Because exponentially growing cells at pH 6.9 had little delta psi (-3 mV) and a slightly reversed Z delta pH (+17 mV), it appeared that the membrane bioenergetics of strain F were solely dependent on Na circulation.
 ...
PMID:Transport and deamination of amino acids by a gram-positive, monensin-sensitive ruminal bacterium. 197 63

A monoclonal antibody raised against beef heart mitochondria elicited a strong reaction on Western Blot with a 16 kD protein in preparations of beef heart mitochondria, ammonia particles, oligomycin sensitive ATPase and Complex V, in addition to showing a lesser affinity for the partially purified 30 kD ADP/ATP carrier. The antibody also reacted with a 17 kD protein in rat liver mitochondria and an enriched membrane vesicle fraction. The N-terminal sequence of the first twenty amino acids of both the beef heart and rat liver proteins contained significant homology. Comparison with results in the literature indicate that the proteins represent the delta subunit of the ATP synthetase complex. Further evidence suggests that the epitope for the antibody may reside at the C-terminal 30-40 amino acid residues of both proteins.
 ...
PMID:Characterization of a low molecular weight protein of the ATP synthetase complex from beef heart and rat liver mitochondria with a high affinity monoclonal antibody. 214 66

The production of 14CO2 from uniformly labeled glucose was shown to account for the entire increase in histamine-stimulated O2 consumption in rabbit gastric glands when no other substrate was added to the medium. The increased production of CO2 was correlated to the increase in O2 consumption and the accumulation of [14C]-aminopyrine (AP) after stimulation with several secretagogues. Inhibitors of H(+)-K(+)-ATPase reduced the secretagogue-induced increase in CO2 production by greater than 90%, showing that the activity of this enzyme was responsible for the greater part of gastric gland metabolism under stimulated conditions. In contrast to AP accumulation, inhibition of CO2 production by omeprazole, an acid-activated inhibitor of the H(+)-K(+)-ATPase, was not reversed by washing. The reversal of AP accumulation after omeprazole treatment and washing was most likely due to a recruitment of residual pumps bordering a nonacidic space, which had not previously been inhibited by omeprazole. These residual pumps slowly generate a pH gradient and hence AP uptake. Adding NH4+ to gastric glands resulted in a concentration-dependent increase of CO2 production up to the maximal stimulated level but without formation of the pH gradient as measured by AP uptake and loss of the omeprazole inhibition of glucose oxidation. As NH4+ can act as a K+ surrogate for H(+)-K(+)-ATPase, and as NH3 is membrane permeant, full stimulation of CO2 production is evidence that the major mechanism of H(+)-K(+)-ATPase activation in situ is an increase in the KCl permeability of the pump membrane.
 ...
PMID:Coupling of H(+)-K(+)-ATPase activity and glucose oxidation in gastric glands. 215 39

The exchange-inert tetra-ammino-chromium complex of ATP [Cr(NH3)4ATP], unlike the analogous cobalt complex Co(NH3)4ATP, inactivated Na+/K(+)-ATPase slowly by interacting with the high-affinity ATP binding site. The inactivation proceeded at 37 degrees C with an inactivation rate constant of 1.34 x 10(-3) min-1 and with a dissociation constant of 0.62 microM. To assess the potential role of the water ligands of metal in binding and inactivation, a kinetic analysis of the inactivation of Na+/K(+)-ATPase by Cr(NH3)4ATP, and its H2O-substituted derivatives Cr(NH3)3(H2O)ATP, Cr(NH3)2(H2O)2ATP and Cr(H2O)4ATP was carried out. The substitution of the H2O ligands with NH3 ligands increased the apparent binding affinity and decreased the inactivation rate constants of the enzyme by these complexes. Inactivation by Cr(H2O)4ATP was 29-fold faster than the inactivation by Cr(NH3)4ATP. These results suggested that substitution to Cr(III) occurs during the inactivation of the enzyme. Additionally hydrogen bonding between water ligands of metal and the enzyme's active-site residues does not seem to play a significant role in the inactivation of Na+/K(+)-ATPase by Cr(III)-ATP complexes. Inactivation of the enzyme by Rh(H2O)nATP occurred by binding of this analogue to the high-affinity ATP site with an apparent dissociation constant of 1.8 microM. The observed inactivation rate constant of 2.11 x 10(-3) min-1 became higher when Na+ or Mg2+ or both were present. The presence of K+ however, increased the dissociation constant without altering the inactivation rate constant. High concentrations of Na+ reactivated the Rh(H2O)nATP-inactivated enzyme. Co(NH3)4ATP inactivates Na+/K(+)-ATPase by binding to the low-affinity ATP binding site only at high concentrations. However, inactivation of the enzyme by Cr(III)-ATP or Rh(III)-ATP complexes was prevented when low concentrations of Co(NH3)4ATP were present. This indicates that, although Co(NH3)4ATP interacts with both ATP sites, inactivation occurs only through the low-affinity ATP site. Inactivation of Na+/K(+)-ATPase was faster by the delta isomer of Co(NH3)4ATP than by the delta isomer. Co(NH3)4ATP, but not Cr(H2O)4ATP or adenosine 5'-[beta,gamma-methylene]triphosphate competitively inhibited K(+)-activated p-nitrophenylphosphatase activity of Na+/K(+)-ATPase, which is assumed to be a partial reaction of the enzyme catalyzed by the low-affinity ATP binding site.
 ...
PMID:How do MgATP analogues differentially modify high-affinity and low-affinity ATP binding sites of Na+/K(+)-ATPase? 216 62

To examine mechanisms of H+ extrusion in the inner stripe of outer medullary collecting duct (OMCDIS), cell pH (pHi) was measured microfluorometrically in in vitro perfused tubules by use of 2',7'-bis(carboxyethyl)-5(6)-carboxyfluorescein. In total absence of luminal and peritubular Na+, pHi recovery from an acid load (NH3/NH+4 pulse) occurred at an initial rate of 0.13 +/- 0.02 pH units/min, whereas in the presence of 135 mM peritubular Na+, pHi recovered at 1.40 +/- 0.28 pH units/min. Na(+)-dependent pHi recovery was completely inhibited by 1.0 mM peritubular amiloride. Luminal Na+ (135 mM) addition had no effect on pHi recovery. Na(+)-independent pHi recovery from acid load was manifest by a triphasic response: 1) initial slow alkalinization; 2) slow cell acidification; and 3) a final phase that exhibited gradually increasing rates of alkalinization, returning pHi above the initial control level (pre-NH3/NH+4 pulse). Luminal N-ethylmaleimide (NEM, 500 microM), an H(+)-ATPase inhibitor, significantly inhibited initial rate of pHi recovery and total pHi recovery; whereas 500 microM peritubular NEM had no effect on initial rate of pHi recovery. Luminal SCH 28080 (100 microM), an H(+)-K(+)-ATPase inhibitor, had no effect on initial rate of pHi recovery or total pHi recovery. Thus rabbit OMCDIS possesses both an apical membrane NEM-sensitive, SCH 28080-insensitive, Na(+)-independent H+ extrusion mechanism (likely a simple H(+)-translocating ATPase) and a basolateral membrane amiloride-sensitive Na(+)-H+ antiporter.
 ...
PMID:Apical and basolateral membrane H+ extrusion mechanisms in inner stripe of rabbit outer medullary collecting duct. 217 59

Relationships between the Na+ dependent amino acid uptake displayed by fertilized sea urchin eggs and the electrochemical gradient of Na+ was investigated. The time course of Na+ content and valine or alanine uptake was simultaneously monitored in Na+ loaded eggs [by fertilization in K+-free artificial sea water (OK-ASW), or by using monensin, antimycin, cyanide, or ciguatoxin]. Our results demonstrate that the uphill amino acid uptake follows the "Na+ gradient hypothesis." Subsequent fertilization of eggs Na+ depleted by ammonia for 40 min stimulates to a great extent the development of amino acid uptake as compared with controls eggs. By using simultaneous change of external and intracellular Na+ concentration, we studied the specific role of this ion. An increase in internal Na+ inhibits the uptake through trans inhibitory action while an increase in external Na+ stimulates the efficiency of the uptake system. In eggs fertilized since 30 min, hyperpolarization obtained in K+-free ASW stimulates amino acid uptake while depolarization (transfer from K+ free ASW to ASW) inhibits it. This potential-dependent effect developed after fertilization with a time course similar to that the establishment of K+ conductance described by R. A. Steinhardt, L. Lundin, and D. Mazia (1971, Proc. Natl. Acad. Sci. USA 68, 2426-2430). In conclusion, our results point out that slight modulations in the activity of the Na+ pump can widely affect the amino acid uptake, suggesting that activation of Na+/K+ ATPase has a key role in the stimulation of amino acid transport.
 ...
PMID:Regulatory and energetic role of Na+ in amino acid uptake by fertilized sea urchin eggs. 242 81


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>