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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)

Salt and water balance in vertebrates in controlled by the release of two blood borne hormones: aldosterone and antidiuretic (ADH). It is the purpose of this chapter to review the mechanisms (at the plasma membrane level) by which these hormones cause an increase in salt (sodium) and water movement in the target tissues. The primary effect of aldosterone is to increase the Na+ permeability of the lumen-facing (apical) membrane by activation of pre-existing quiescent channels at short times, and by the incorporation of newly synthesized channels after prolonged exposure. Other effects might involve an increase in energy supply and synthesis of Na+-K+ ATPase which is responsible for Na+ extrusion from cell cytoplasm to blood. Similarly, ADH stimulates pre-existing quiescent apical membrane Na+ channels. The second effect of ADH is to increase epithelial water permeability. Evidence strongly suggests that water channels exist in cytoplasmic vesicles which, upon ADH challenge, fuse into the apical membrane causing a rapid increase in apical membrane hydraulic conductivity. The movements of vesicles are dependent on an intact cytoskeleton. Regulation of electrolyte and non-electrolyte transport will be discussed in the light of the above two mechanisms.
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PMID:Control of Na+ and water absorption across vertebrate "tight epithelia by adh and aldosterone. 631 91

1. The redox state of mitochondrial NAD was monitored fluorometrically as a function of active ion transport work in the isolated doubly perfused bullfrog kidney. 2. Initial experiments to measure the O2 consumption (QO2) of small pieces from the bullfrog kidney gave a basal QO2 - 3.0 (+/- 0.43) nmoles O2/mg dry wt. min. Addition of 50 microM-ouabain inhibited QO2 by 72.7%. Subsequent addition of the mitochondrial uncoupler 1799 stimulated QO2 by 226%, while cyanide totally inhibited respiration. 3. Ion transport functional parameters and NADH fluorescence were simultaneously monitored during systematic reductions in perfusate PO2 to test the sufficiency of O2 delivery to the isolated perfused frog kidney. No significant changes in transport functions or fluorescence were observed until the PO2 dropped to 184 mm Hg or below. O2 tensions of 184 mm Hg or below caused decreases in G.F.R. and transport functions which were accompanied by an increase in NADH fluorescence. The lack of changes in kidney function in the PO2 range 550-340 mmHg suggested that the tissue is adequately oxygenated at the normal perfusate PO2 of 550 mmHg. 4. The relationship between active transport rate and NAD redox levels was studied by increasing transport work (via increased G.F.R. or ADH) or by decreasing transport work (via decreased G.F.R. or ouabain) while simultaneously monitoring the NAD redox state of the intact tissue fluorometrically. In all cases, an increase in work caused a net oxidation of NAD while a decrease in work caused a reduction of NAD. 5. It is concluded that the NADH fluorescence responses are indicative of mitochondrial active to passive transitions in response to changes in active transport work. The aerobic production of ATP and the normally functioning Na-K-ATPase appear to be essential to maintain active transport and to elicit the appropriate state transitions. Thus, ATP (and, possibly, ADP and Pi) may be part of the coupling mechanism linking active ion transport and aerobic metabolic rate in the kidney.
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PMID:Coupling of aerobic metabolism to active ion transport in the kidney. 696 4

We assessed the effects of antidiuretic hormone and cyclic adenosine monophosphate (cAMP) analogues on transepithelial voltage, Ve, and/or net chloride absorption in isolated mouse medullary (mTALH) and cortical (cTALH) thick ascending limbs of Henle; the passive NaCl permeability characteristics and electrical properties of the mTALH; and the effects of anion and cation substitutions and transport inhibitors on both basal and ADH-stimulated Ve and/or net chloride absorption in the mTALH. The data demonstrate that these two segments are functionally heterogeneous: ADH, at concentrations comparable to plasma levels seen in mammalian species during ordinary antidiuresis, and/or cAMP increase three- to fourfold the rate of NaCl absorption in the mTALH but not in the cTALH. The ion substitution and inhibitor data are consistent with the view that NaCl absorption in the mTALH depends on a secondary active transport process: NaCl entry across luminal membranes is a coupled process of indeterminate stoichiometry that is driven by the transmembrane electrochemical gradient for Na+, which is maintained by Na+-K+-ATPase. Finally, the data demonstrate that the mTALH is electrically leaky whether measured electrically, 11 omega . cm2, or isotopically, 50 omega . cm2, but essentially water impermeable; and that the mTALH is perm-selective for Na+ with respect to Cl-. The disparity between electrical resistances measured directly with respect to those calculated from tracer fluxes, together with the hybrid characteristics of mTALH junctional complexes (leaky to Na+ and Cl-; tight to water), may be reconciled by assuming that mTALH junctional complexes contain passive ion permeation pathways composed of narrow channels through which ions pass in single-file fashion.
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PMID:NaCl transport in mouse medullary thick ascending limbs. I. Functional nephron heterogeneity and ADH-stimulated NaCl cotransport. 731 65

Gastric intubation of female Sprague-Dawley rats (80-150 g) with one large dose (5 g/kg) of ethanol nearly doubled oxygen uptake of the isolated, perfused rat liver in only 2.5 hours. This increased hepatic respiration can account for the Swift Increase in Alcohol Metabolism (SIAM). Inhibition of enhanced oxygen and ethanol uptake by KCN (2 mM) and 4-methylpyrazole (0.8 mM) indicated the involvement of the mitochondrial respiratory chain and alcohol dehydrogenase in this phenomenon, respectively. Epinephrine (2 mg/kg, i.p.) mimicked the increase in respiration observed with ethanol; however, the effects of epinephrine and ethanol were not additive. Pretreatment with alpha- and beta-adrenergic blocking agents, hypophysectomy and adrenalectomy prevented the increase in oxygen and ethanol uptake due to ethanol treatment. These data suggest that hormones including epinephrine are involved in the mechanism of SIAM. Hormone action in all likelihood activates a number of metabolic ATPase activities which lead to elevated oxygen uptake. One such process involved in the activation of oxygen uptake is diminished glycolysis, a ATP producing reaction sequence. The ADP not phosphorylated in the cytosol then enters the mitochondria where it stimulates oxygen uptake and NADH reoxidation. This ultimately leads to an acceleration of ADH-dependent ethanol metabolism.
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PMID:Mechanism of the swift increase in alcohol metabolism ("SIAM") in the rat. 742 36

The present overview indicates that the various nephron segments take part in the Na+Cl- reabsorption, the primary driving force for it is the (Na+, K+)-ATPase, which is localized in the basolateral membrane. The various segments have different modalities of Na+ uptake: in is by Na+/H+ exchange in the proximal tubule, by Na+/2Cl-/K+ co-transport in TAL, Na+Cl- cotransport in the distal tubule, and via Na+ channels in the principal cell of the collecting duct. In the proximal tubule bulk reabsorption occurs, but very small ionic gradients are built up, there for the transport here is so economical. In the TAL transport is already less economical, however ionic gradients are built up by this nephron segment inasmuch as Na+Cl- is reabsorbed and water cannot follow (the urinary concentrating mechanism). The distal tubule is concerned with defined control of Na+ and K+ excretion. Transport at this side is expensive, but very steep ionic gradients can be built up. The control is mediated by several hormones amongst which ADH and aldosterone are the most important ones.
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PMID:[The principles of studying ion transport in the kidney tubules]. 753 Oct 74

Fluoride released from methoxyflurane (MOF) during its hepatic and extrahepatic metabolism has been regarded as the major culprit responsible for MOF-induced nephrotoxicity. In the isolated, perfused rat kidney model, admixture of 1500 mumol/l fluoride to the perfusate resulted in tubular and glomerular damage with concomitant anuria. Fluoride administration in Fischer 344 rats in vivo elicited a renal diabetes insipidus-like syndrome that had also been observed in patients after MOF anaesthesia. The renal concentrating defect is most probably due to both dissipation of the corticomedullary osmolality gradient in the interstitium and failure of water reabsorption due to ADH refractoriness of the distal tubular cells. Hypothetically, the underlying mechanism may be a fluoride-induced inhibition of enzymes involved in intracellular energy production such as ATPase or enolase. The degree of nephrotoxicity correlates loosely with maximal serum fluoride levels, but can probably be modulated by further factors like intrarenal in situ formation of fluoride, urinary pH and flow, and especially, the presence of other nephrotoxins. This mitigates the importance of maximal fluoride serum levels, especially the 50 mumol threshold, as predictors of clinically relevant nephrotoxicity. To date, no nephrotoxic effects of sevoflurane could be demonstrated.
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PMID:[Nephrotoxicity and fluoride from the viewpoint of the nephrologist]. 877 2

This review will discuss generalized myxedema as it develops in hypothyroidism. First, the precipitating conditions (thyroprivic trophoprivic + goitrous forms) and the clinical manifestations of thyroid hormone deficiency are presented. Pathobiochemical and pathophysiological factors that lead to the main manifestations include retention of fluid, retention of sodium and hyponatremia. In particular are primary and direct consequences of reduced thyroid hormone levels, and secondary or indirect consequences, such as cardiovascular and renal derangements. In hypothyroidism many biochemical disturbances result. Most important is the interstitial deposition of hydrophilic mucopolysaccharides, which in turn lead to fluid and Na retention and impairment of blood circulation and lymphatic drainage. Myxedema, therefore, is to a large extent a lymphatic edema. Hyponatremia is an indirect consequence of the lack of T3 and is directly caused by impaired renal Na reabsorption. Renal Na,K-ATPase is reduced in specific segments. The often discussed role of inappropriate elevation of circulating ADH does not seem to be a key factor in myxedema. Impaired capacity of renal water excretion is caused by reduced GFR. We discuss the time dependent development of the derangement of different organ systems, and include recently published biochemical results, according to which the lack of T3 interferes not only with the metabolism of numerous compounds of the interstitial matrix, but also with cell surface proteins and intracellular proteins of microfilaments. Finally, we refer briefly to pretibial myxedema in states of hyperthyroidism, that is, infiltrative dermopathy in Graves' disease, which is caused by poorly understood autoimmune processes.
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PMID:Myxedema. 918 11

The lipid peroxidation product 4-hydroxynonenal (4-HNE) has been shown to interfere with protein function. The goal of this study was to determine the effects of substrate modification by 4-HNE on protein degradation. Equine liver alcohol dehydrogenase (ADH, EC 1.1.1.1) treated with 2-fold molar excess 4-HNE was degraded by a rabbit reticulocyte lysate (RRL) system approximately 1.5-fold faster than control, while treatment with concentrations up to 100-fold molar excess aldehyde were inhibitory to degradation. Involvement of the 26S proteasome (EC 3.4.99.46) was demonstrated through the use of specific proteasome and ATPase inhibitors, and confirmed by measuring the extent of ADH polyubiquitination. Tryptic digestion and LC/MS analysis of 4-HNE-treated ADH identified modification of two zinc chelating Cys residues. Through molecular modeling experiments a conformational shift in both zinc-containing regions was predicted, with an approximate doubling of the distance between the structural zinc and its respective chelating residues. Modification of residues in the active site zinc binding motif resulted in less pronounced alteration in protein structure. The data presented here demonstrate accelerated ubiquitination and proteasomal degradation of ADH modified with 4-HNE, and suggest a conformational change after 4-HNE docking as a mechanism behind these observations.
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PMID:4-Hydroxynonenal regulates 26S proteasomal degradation of alcohol dehydrogenase. 1545 82

We have examined the role of alcohol dehydrogenase (ADH, E.C.1.1.1.1) in chilling tolerance using maize (Zea mays L.) Adh1(-)Adh2(-) doubly null mutant. Adh1(-)Adh2(-) doubly null seedlings were found to have lowered survival rates compared to non-doubly null maize seedlings (Silverado F(1)) when held at 2 degrees C for varying periods. Exposure to ethanol did not increase the chilling tolerance in either Silverado F(1) or Adh1(-)Adh2(-) doubly null. ADH activity in Silverado F(1) remained steady when held at 2 degrees C for up to 3 d. ADH1 protein accumulation in chilled Silverado F(1) seedlings remained unchanged throughout the period of cold exposure. Chilling led to a significant inhibition of the P-H(+)-ATPase (E.C. 3.6.3.6) activity in Adh1(-)Adh2(-)doubly null, but minimal inhibition was seen in Silverado F(1). Though P-H(+)-ATPase activity in Adh1(-)Adh2(-) decreased, P-H(+)-ATPase protein levels remained constant during the chilling period. Levels of ATP slightly fluctuated in both types of seedlings during the duration of chilling. Lipid peroxidation levels in Adh1(-)Adh2(-) doubly null increased with chilling exposure, but not in the Silverado F(1). We suggest that ADH activity may play a role in chilling tolerance that is not related to maintenance of glycolysis and ATP production as has been observed during oxygen depravation.
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PMID:Relationship between alcohol dehydrogenase activity and low-temperature in two maize genotypes, Silverado F1 and Adh1-Adh2- doubly null. 1559 4

Although we are used to attribute almost identical extracellular fluid (ECF) sodium concentrations in birds, amphibians, reptiles, and mammals to the composition of the primordial oceans in which, presumably, all life originated, this interpretation is not supported by geological data suggesting that the ocean salinity was never much lower than the present-day values, still four times higher than our plasma sodium. Here presented interpretation is that the similar ECF salt concentrations are dictated by the opposed Donnan effects on the cell membrane. The only way for the cell to reach the osmotic equilibrium is to alter cell volume, until concentration of nondiffusible intracellular ions (mainly charges on intracellular proteins) is equal to the ECF restricted ions (mainly Na+ ions, restricted by pumping out of cells). The achievement of electroneutrality requires that the sum of all anions equals concentration of positive ions in the cell (mainly K+). Negative charges on cytoplasmic proteins are the most stable component among ionized particles and other ions have to adapt to their concentration. Positive and negative soluble intracellular ions are all osmotically active and to achieve balance of osmotic forces on the cell membrane, the sum of their intracellular concentrations must equal the concentration of osmotically active extracellular particles. Since almost half the osmotically active ECF particles are sodium ions, the ECF sodium concentration seems related to concentration of charges on cytoplasmic proteins and concentration of intracellular phosphates. Our ancestors could not leave the salty ocean and move to brackish, or even fresh waters, without adequate regulation of their ECF sodium concentration and osmolality. Concentration of charges on cytoplasmic proteins or of intracellular phosphate buffers could not be altered, since this would compromise cell functioning. The remaining solution was to maintain the lowest ECF Na+ concentration effective in counteracting the average Donnan effect of charges on cytoplasmic proteins. When the optimal ECF sodium concentration had once become the reference point for osmoreceptors (controlling thirst and ADH secretion) and other regulatory mechanisms (secretion of renin/angiotensin/aldosterone, natriuretic factors), it made an important survival advantage that allowed spreading of animal life in fresh water and conquering of earth. The actual common value had to be a compromise that reduces the average osmotic burden on body cells to zero. Individual cells can reduce eventual residual osmotic forces on their membrane through altering cell volume by chloride shift, and by modulating the Na+K+-ATPase function.
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PMID:Are extracellular osmolality and sodium concentration determined by Donnan effects of intracellular protein charges and of pumped sodium? 2011 87


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