Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0027960 (mole)
 21,279 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

(Na+ + K+)-ATPase from shark rectal glands reconstituted into lipid vesicles and oriented inside out catalyses an ouabain-sensitive Na+-Na+ exchange in the absence of intravesicular K+ when ATP is added extravesicularly. Intravesicular ouabain inhibited the exchange completely. This was also the case with digitoxigenin added to the vesicles. Intravesicular oligomycin inhibited the Na+-Na+ exchange partly in a fashion which was ATP dependent. The exchange is accompanied by a net hydrolysis of ATP with an apparent Km of 2.5 microM. ADP was found to give no stimulation of the Na+-Na+ exchange, contrarily, ADP inhibited the ATP-dependent exchange of Na+ both at optimal and supraoptimal ATP concentrations. When initial influx and efflux of 22Na was measured and the hydrolysis of ATP concomitantly determined a coupling ratio of 2.8:1.3:1 was found, i.e. 2.8 moles of Na+ were taken up (cellular efflux) and 1.3 moles of Na+ extruded (cellular influx) for each mole of ATP hydrolyzed. The electrogenic Na+-Na+ exchange generated a transmembrane potential which was measured with the fluorescent probe ANS (8-anilino-1-naphthalenesulfonic acid) to be 60 mV positive inside the liposomes (extracellular).
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PMID:Na+-Na+ exchange mediated by (Na+ + K+)-ATPase reconstituted into liposomes. Evaluation of pump stoichiometry and response to ATP and ADP. 299 89

The kinetics of hydrolysis of ATP were determined for the renal Na,K-ATPase, in the K+ conformation, modified with glucose-6-phosphate. There was a shift in the ATP hydrolysis kinetics from negative kinetic co-operativity for the control enzyme preparations to substrate inhibition kinetics for the modified enzyme preparations. The effect was reversible and stabilized after NaBH4 reduction. Approximately 4 moles of glucose-6-phosphate were incorporated per mole of Na,K-ATPase (based on MW of 150,000 daltons). Similar substrate inhibition kinetics were observed for the renal Na,K-ATPase isolated from several human subjects with mature onset diabetes.
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PMID:Glucose-6-phosphate modification of bovine renal Na,K-ATPase: a model for changes occurring in the human renal medulla in diabetes. 299 41

N,N'-Dicyclohexylcarbodiimide (DCCD), a reagent that reacts with carboxyl groups under mild conditions, irreversibly inhibits (Na+,K+)-ATPase activity (measured by using 1 mM ATP) with a pseudo-first-order rate constant of 0.084 min-1 (0.25 mM DCCD and 37 degrees C). The partial activities of the enzyme, including (Na+,K+)-ATPase at 1 microM ATP, Na+-ATPase, and the formation of enzyme-acyl phosphate (E-P), decayed at about one-third the rate at which (Na+,K+)-ATPase at 1 mM ATP was lost. The formation of E-P from inorganic phosphate was unaffected by DCCD while K+-phosphatase activity decayed at the same rate as (Na+,K+)-ATPase measured at 1 mM ATP. The enzyme's substrates (i.e., sodium, potassium, magnesium, and ATP) all decreased the rate of DCCD inactivation of (Na+,K+)-ATPase activity measured at either 1 mM or 1 microM ATP. The concentration dependence of the protection afforded by each substrate is consistent with its binding at a catalytically relevant site. DCCD also causes cross-linking of the enzyme into species of very high molecular weight. This process occurs at about one-tenth the rate at which (Na+,K+)-ATPase activity measured at 1 mM ATP is lost, too slowly to be related to the loss of enzymatic activity. Labeling of the enzyme with [14C]DCCD shows the incorporation of approximately 1 mol of DCCD per mole of large subunit; however, the incorporation is independent of the loss of enzymatic activity. The results presented here suggest that (Na+,K+)-ATPase contains two carboxyl groups that are essential for catalytic activity, in addition to the previously known aspartate residue which is involved in formation of E-P.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Inhibition of (Na+,K+)-ATPase by dicyclohexylcarbodiimide. Evidence for two carboxyl groups that are essential for enzymatic activity. 300 Apr 36

The (Na+ + Mg2+)-ATPase of the Acholeplasma laidlawii B plasma membrane was inactivated by the 2',3'-dialdehyde derivative of ATP (oATP). oATP behaved as a reversible competitive inhibitor of this ATPase and was slowly hydrolyzed by the enzyme. In addition, oATP induced an irreversible inactivation of the enzyme. A 62% inactivation of the enzyme correlated with the binding of 16 moles of oATP per mole of the enzyme. In the presence of 5'-adenylyl imidodiphosphate, a non-hydrolyzable substrate analogue, the stoichiometry was 8 moles oATP per mole of ATPase. By SDS-polyacrylamide gel electrophoresis, [U-14C]oATP was found to bind covalently to four of the five subunits of the enzyme, but specific labeling was highest for the gamma-subunit of the ATPase.
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PMID:Affinity labeling of the (Na+ + Mg2+)-ATPase from Acholeplasma laidlawii B membranes by the 2',3'-dialdehyde derivative of adenosine 5'-triphosphate. 315 67

There are one or more proteins of 50,000 to 60,000 Mr in the thin filaments of insect flight muscle. A protein of 55,000 Mr has been isolated from insect fibrillar flight muscle and called arthrin. Despite its higher molecular weight, arthrin is in many ways like actin. The amino acid composition of arthrin was similar to that of actin. There were similarities in the peptides produced by digesting the denatured proteins and mild digestion of polymerized proteins cleaved similar-sized fragments from arthrin and actin. Polymerized arthrin activated the Mg2+ ATPase of myosin to the same extent as actin and the ATPase was regulated by rabbit or Lethocerus troponin and tropomyosin. Arthrin did not itself act as troponin-T. Electron microscopy of negatively stained specimens showed that arthrin and actin filaments were similar in structure and that arthrin could be decorated by rabbit subfragment-1 to form normal-looking arrowheads. Arthrin formed paracrystals at an optimum concentration of MgCl2 (25 mM) that was somewhat lower than the optimum for actin paracrystals. Optical diffraction showed that the structure of the paracrystals was similar to those formed from actin. The mass of arthrin and actin filaments relative to phage fd was measured by scanning transmission electron microscopy; the relative mass of arthrin and actin was 1.33, in agreement with molecular weight estimations. Therefore arthrin has the properties of a heavy form of actin. The proportion of actin, arthrin and troponin-T in Lethocerus myofibrils was six moles of actin to one mole of arthrin and one mole of troponin-T. The function of arthrin is not known.
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PMID:Arthrin: a new actin-like protein in insect flight muscle. 315 2

Phosphorus 31 magnetic resonance spectroscopy (31P MRS) was used to study noninvasively the intracellular free Mg2+ concentration and cellular bioenergetic state of rat brain in vivo before and after fluid percussion-induced traumatic brain injury of graded severity. Brain injury was induced at four levels: low (1.0 +/- 0.5 atm); moderate (2.1 +/- 0.4 atm); high (3.9 +/- 0.9 atm); and severe (5.9 +/- 0.7 atm). Prior to injury, mean intracellular values for all groups (n = 24; mean +/- SE) were as follows: pH = 7.11 +/- 0.03; free [Mg2+] = 0.99 +/- 0.07 mM; cytosolic [ADP] = 25.2 +/- 0.8 nmol/g wet weight; cytosolic [AMP] = 0.29 +/- 0.02 nmol/g wet weight; cytosolic phosphorylation potential = 118.5 +/- 3.1 X 10(3) M-1; free energy of ATP hydrolysis = 62.11 +/- 0.04 kJ/mole; and energy charge = 0.99 +/- 0.01. Following every level of injury, there were decreases in intracellular free Mg2+ concentration, and alterations in the intracellular pH. These posttraumatic changes in Mg2+ and pH induced shifts in the equilibrium constants of the creatine kinase, adenylate kinase, and ATPase reactions, resulting in alterations in [ADP], [AMP], cytosolic phosphorylation potential, and free energy of hydrolysis, but not in the energy charge. The alterations in cytosolic phosphorylation potential following trauma were linearly correlated with the changes in intracellular free Mg2+ concentration. None of the individual bioenergetic parameters could be correlated with the severity of injury over the entire injury range; however, an association between cytosolic phosphorylation potential and reversibility of injury was apparent. These results suggest that reductions in cellular bioenergetic state following traumatic brain injury occur through a posttraumatic decrease in the cells' capacity for oxidative phosphorylation, which itself may be directly related to the intracellular free Mg2+ concentration.
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PMID:Changes in cellular bioenergetic state following graded traumatic brain injury in rats: determination by phosphorus 31 magnetic resonance spectroscopy. 324 10

The ability to induce alcoholic cardiomyopathy has been tested in a variety of animal species. Myocardial alterations consistent with subclinical heart disease have been produced in many of these studies through a direct effect of ethanol or its metabolites upon the heart or a neurohumoral mechanism. In the rat most studies have, however, failed to finding diminished contractility in the basal state. In long-term animals the acute left ventricular responses to isoproterenol and calcium as well as pacing were reduced. Long-term studies in mongrel dogs fed 36 per cent of calories as ethanol produced an early decrease in left ventricular diastolic compliance related to interstitial collagen accumulation. Diminished contractility developed by four years. In addition to the morphologic evidence of distorted sarcoplasmic reticulum, in vitro experiments suggest important acute effects. Each mole of ethanol is bound tightly to each mole of protein comprising the Ca-ATPase pump, which is inhibited. Impaired uptake and binding of calcium by the sarcoplasmic reticulum has been observed in chronic alcohol models at one to two day intervals following the last exposure to ethanol. In addition, the flux of calcium ion does not appear normal in terms of access to contractile protein, where the calcium regulated inhibition of the troponin interaction with myosin is impaired. Experimental studies in a canine model of alcoholism revealed that the ventricular fibrillation threshold was moderately reduced in the basal state after 18 months and was diminished further after acute exposure.
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PMID:Experimental models for studying the effects of ethanol on the myocardium. 331 64

The isolated rat jejunal slice was used to determine if aluminum (Al) interacts with the gastrointestinal (GI) calcium (Ca) transporting system. Al uptake by the rat jejunal slice was reduced by Ca channel blockers (verapamil, nifedipine, diltiazem-10 microM) and a medium containing no added Ca. Conversely, Al uptake was increased by Ca channel activators (4-aminopyridine, .05mM, .1mM; Bay k 8644, 1, 10 microM) and by 5mM Ca. Al uptake was saturable and energy dependent but yielded a low activation energy (Ea = 3.9 +/- 0.3 kcal/mole). Al uptake was increased by vanadate (100 microM), an inhibitor of both the active Ca pump and Na/K-ATPase. These results suggest that Al does interact with the GI Ca transporting system. This interaction may form the basis for its accumulation and toxicity in different tissues which contain similar processes for handling Ca.
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PMID:Influence of calcium on aluminum accumulation by the rat jejunal slice. 335 81

We have recently shown that inositol 1,4,5-trisphosphate (IP3) releases Ca2+ from the endoplasmic reticulum of pancreatic acinar cells and suggested that IP3 may function as a second messenger of hormonal receptors to mobilize Ca2+ from intracellular stores (Streb et al, 1983, Streb et al, 1984). In rat kidney cortical tubules and microdissected mouse proximal tubules, an increased turnover of polyphosphoinositide metabolism following hormonal stimulation with angiotensin II-amide and phenylephrine has been reported (Wirthensohn et al, 1984; Wirthensohn et al, 1985). This suggests that IP3, one of their hydrolysis products, increases during hormonal stimulation. We therefore investigated the effect of angiotensin II-amide and IP3 on intracellular Ca2 stores in saponin-treated cells and homogenate from rat kidney cortex. Saponin-treated isolated cortical kidney cells or homogenate was incubated in a high K+ buffer in the presence of MgATP and respiratory substrates. Ca2+ uptake was determined by measuring the free Ca2+ concentration of the surrounding medium with a Ca2+ specific macroelectrode. Addition of cells or homogenate to the incubation medium resulted in a decrease of the medium free Ca2+ concentration until a steady-state concentration of 5.7 +/- 0.2 X 10(-7) mole/l was obtained. In the presence of mitochondrial inhibitors Ca2+ uptake rate was reduced, whereas the steady-state concentration was unchanged. In contrast, in the presence of the CA2+-ATPase inhibitor vanadate mitochondrial uptake proceeded at the same rate as the control, but the steady-state concentration was higher (6.9 +/- 0.2 X 10(-7) mole/l).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Inositol 1,4,5-trisphosphate releases Ca2+ from a nonmitochondrial store site in permeabilized rat cortical kidney cells. 348 13

The role of orthophosphate ions (Pi) in crossbridge kinetics was investigated by parallel measurements of the ATP hydrolysis rate and tension transients in maximally activated, chemically skinned rabbit psoas fibers. The hydrolysis rate of the standard activation at 20 degrees C was measured at 1.25 nmole X s-1 X m-1 X fiber-1, which corresponds to the hydrolysis of 3 moles ATP per mole of myosin head per second. The isometric tension, stiffness extrapolated to the infinite frequency, and the ATPase rate progressively decreased when increasing concentrations of Pi (0-16 mM) were added to the activating saline. The decrease was greatest with tension, followed by stiffness and the ATPase rate. Both the apparent rate constant and the magnitude parameters of exponential process (B) increased with Pi concentration resulting in a significant increase in the oscillatory power output. The effects of Pi on processes (A) and (C) were only marginal. When fibers were oscillated at 1 Hz [close to the characteristic frequency of process (A)], no significant increase in the ATP hydrolysis rate was observed. However, a small increase was noticed at 10 Hz [1%, process (B)], and at 100 Hz [6%, process (C)]. We interpret these results in terms of a crossbridge scheme which adds a branch pathway to the conventional hydrolysis cycle. In the proposed scheme, the number of crossbridges entering the branch pathway increases at higher Pi concentrations and in the presence of imposed oscillations at the proper frequency.
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PMID:The effect of inorganic phosphate on the ATP hydrolysis rate and the tension transients in chemically skinned rabbit psoas fibers. 382 68


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