Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The Ca2+-dependent ATPase was solubilized from rat heart sarcolemmal membranes upon digestion with trypsin and was found to be different from Ca2+-stimulated Mg2+-dependent ATPase (Dhalla, N. S., Anand-Srivastava, M. B., Tuana, B. S., and Khandelwal, R. L. (1981) J. Mol. Cell. Cardiol. 13, 413-423). The enzyme was purified by high speed centrifugation, ammonium sulfate fractionation, and column chromatography and was seen as a single protein band in nondenaturing polyacrylamide gel electrophoresis. In sodium dodecyl sulfate-acrylamide gels, the enzyme dissociated into two subunits or fragments with molecular weights of about 55,000 and 12,000. The molecular weight of the enzyme, estimated by gel filtration on a Sephadex G-100 column, was found to be about 67,000. The enzyme utilized ATP with a Km of 0.20-0.26 mM but was also able to utilize ITP, CTP, GTP, and ADP as substrates at much lower rates. It was activated by Ca2+ with a Ka of 0.13-0.21 mM; it was also activated by other cations in the order Ca2+ greater than Mn2+ greater than Sr2+ greater than Ba2+ greater than Mg2+. Divalent cations like Cu2+, Ni2+, and Mg2+ were potent inhibitors. The enzyme was insensitive to ouabain, verapamil, oligomycin, cyanide, and vanadate but was markedly inhibited by N-ethylmaleimide. Calmodulin failed to stimulate Ca2+-dependent ATPase and instead inhibited slightly. Unlike K+, Na+ produced a marked inhibition of the Ca2+-dependent ATPase activity, and this inhibition was associated with an 8- 10-fold decrease in the affinity of the enzyme for Ca2+. The competitive action of Na+ indicates that the Ca2+-dependent ATPase may be a site of Na+-Ca2+ antagonism in the cell membrane.
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PMID:Purification and characterization of a Ca2+-dependent ATPase from rat heart sarcolemma. 621 55

The flow of electrons the terminal oxidases present in the bloodstream and procyclic trypomastigotes of Trypanosoma brucei LUMP 1026 has been investigated by the use of salicylhydroxamic acid (SHAM) and cyanide. Respiration in bloodstream trypomastigotes was completely inhibited by 0.5 mM SHAM with a Ki below 10 microM. The Ki for SHAM in procyclic trypomastigotes was 70 microM. In procyclic trypomastigotes there are at least three terminal oxidases of which the two major ones are cytochrome aa3 oxidase, sensitive to cyanide inhibition, and alpha-glycerophosphate oxidase (GPO), sensitive to SHAM inhibition. These two oxidases contribute 60 and 30%, respectively, to total cell respiration. Inhibition of the cytochrome system with cyanide causes an increase in the flow of electrons through the GPO system, and inhibition of the GPO system with SHAM stimulates electron flow in the cytochrome system. Succinate oxidation in the mitochondrial fraction is partially inhibited by SHAM and this SHAM-sensitive respiration is not inhibited by antimycin A. The kinetic data of respiration by procyclic trypomastigotes fit a model proposed by Bahr and Bonner to determine the maximum rates of two competing electron transport pathways. It is concluded that the electron transport chain in T. brucei is branched.
Mol Biochem Parasitol 1980 Mar
PMID:Evidence for a branched electron transport chain in Trypanosoma brucei. 625 26

Messenger RNA is released preferentially from isolated rat liver nuclei in the presence of the ATP-generating system and cytosol. The release is suppressed by spermidine, while cytoplasmic RNase inhibitor was ineffective and PCMB like some other thiol-blocking agents inhibitory. Cytoplasmic SOD added to the system strongly suppressed RNA release. A similar effect could be obtained by anaerobiosis due to addition of SMP. In both cases the inhibition is reversed by cyanide. In contrast to normal liver where the generation of superoxide radicals takes place almost exclusively in microsomes and is coupled with the oxidation of NADPH, in mouse ascites hepatoma 22a the generation of superoxide radicals occurs mainly in the nuclear envelope and is coupled wih the oxidation of both NADPH and NADH and inhibited by cyanide.
Mol Biol Rep 1981 May 22
PMID:Some features of nucleo-cytoplasmic RNA transport from isolated nuclei. 626 58

Ro 11-2465 is a cyanide derivative of imipramine. In cerebral cortex homogenates, [3H] Ro 11-2465 displays a binding profile similar to that of [3H]imipramine. Agents compete with binding of [3H]Ro 11-2465 in an order of potency similar to their ability to block serotonin uptake, and raphe lesions greatly decrease the binding of [3H]Ro 11-2465. These observations suggest that the sites labeled by [3H]Ro 11-2465 are presynaptic. The binding of [3H]Ro 11-2465 is sodium ion-dependent, as are both the binding of [3H] imipramine and the serotonin uptake mechanism. In the presence of sodium ions, binding of [3H]Ro 11-2465 to brain tissue or platelets at 4 degrees is apparently irreversible. Binding is not displaced by high concentrations of the displacing agent desipramine or by repeated washing. However, by either removing sodium or increasing the assay temperature to 23 degrees, the ligand dissociates from the tissue. In tissue where [3H]Ro 11-2465 is irreversibly bound to receptor at 4 degrees, subsequent [3H]imipramine binding is decreased by about 50%. At temperatures greater than 23 degrees, [3H]Ro 11-2465 binding displays a temperature dependency similar to that of [3H]imipramine; that is, when temperatures are raised from 23 degrees to 30 degrees or 37 degrees there is no change in the Bmax, but the affinity of the ligand for the receptor is decreased. These data suggest that [3H]Ro 11-2465 binds to a discrete population of [3H]imipramine binding sites, comprising about one-half of the total [3H] imipramine binding sites.
Mol Pharmacol 1983 May
PMID:Binding of [3H]Ro 11-2465. Possible identification of a subclass of [3H]imipramine binding sites. 630 30

Mechanical performance, energy-rich phosphates and cyclic nucleotides of frog heart were measured during energetic deficiency and subsequent addition of adrenaline. When oxidative metabolism was inhibited by 3 mM cyanide, tension decrease was accompanied by a decrease in creatine phosphate while ATP and cyclic nucleotides did not vary significantly. After subsequent addition of adrenaline mechanical activity remained less than control value; creatine phosphate (CP) concentration was further decreased while cAMP was increased in the same proportion as when adrenaline alone was added. In the presence of cyanide, the weak inotropic effect of adrenaline is not due to an alteration of cyclic nucleotides but is rather correlated to a further decrease in energy-rich phosphates, mainly in creatine phosphate. These results suggest that creatine phosphate may control contractile activity and may be a limiting factor for inotropic interventions at least during energetic inhibition.
J Mol Cell Cardiol 1983 May
PMID:Role of cyclic nucleotides and energy-rich phosphates during energetic deficiency in frog heart. 631 Jan 29

This review of retinal pigment epithelial (RPE) physiology pays tribute to Anthony L. F. Gorman, who introduced the author to the giant neuron of Anisodoris nobilis (the sea lemon) and cellular neurobiology. The RPE is an epithelial monolayer with tight junctions, which controls the environment of the photoreceptor outer segments. The apical and basal membranes have different electrical properties and generate a standing potential across the eye. The RPE helps maintain adhesion between the retina and the wall of the eye. Adhesion is weakened by cyanide, low pH or low calcium, but enhanced by ouabain or acetazolamide. The RPE transports water from the subretinal space toward the choroid. This water movement is inhibited by hypoxia or cyanide but enhanced by ouabain or acetazolamide. The c-wave of the electroretinogram is a composite of a cornea-positive wave produced by hyperpolarization of the apical RPE membrane and a cornea-negative wave produced by the Muller cells, both in response to the fall in extracellular potassium that follows illumination of the photoreceptors. The "light response" of the standing potential is produced by depolarization of the basal membrane of the RPE. These examples illustrate how principles of cellular neurophysiology can be applied to questions of clinical relevance.
Cell Mol Neurobiol 1983 Dec
PMID:From sea lemons to c-waves. 632 7

Uncertainty exists regarding the mechanisms of Ca efflux from isolated myocardial cells. Therefore, transmembrane fluxes of Ca, exchangeable Ca content, and contractile behavior were studied in monolayers of cultured chick embryo-ventricle during abrupt exposure to media containing zero [Na]o (choline chloride substitution). Exposure to zero [Na]o induced a transient contracture of cultured heart cells. Rapid Ca influx increased significantly over the first 60 s immersion in zero [Na]o; however, total exchangeable Ca content, measured by labelling with 45Ca, did not change, suggesting that rapid Ca efflux was also increasing under these conditions. When 45Ca in the extracellular space was removed by washing for 16 s in ice cold buffer before 45Ca efflux was measured, an increase in Ca efflux with exposure to zero [Na]o was apparent. Treatment of cells with 10(-3) M cyanide and 20 mM 2-deoxyglucose resulted in a decrease in the Ca efflux in zero [Na]o-zero [Ca]o medium, and in the appearance of significant components of [Na]o and [Ca]o-dependent Ca efflux. These results are consistent with the hypothesis that Ca efflux in these cells normally occurs predominantly by a non-[Na]o-dependent mechanism, probably an ATP-dependent Ca pump. After metabolic blockade of ATP production with a resulting increase in Ca loading of the cytoplasm, increased efflux of Ca via Na Ca and Ca Ca exchange occurs.
J Mol Cell Cardiol 1984 Feb
PMID:Movement of Ca2+ across the sarcolemma: effects of abrupt exposure to zero external Na concentration. 632 13

Two studies on the abiotic formation of amino acids are presented. The first study demonstrates the role of hydrogen cyanide as a precursor of amino acids detected in extracts of lunar samples. The formation of several amino acids, including glycine, alanine, aspartic acid, and glutamic acid, under conditions similar to those used for the analysis of lunar samples is demonstrated. The second study investigates the formation of hydrogen cyanide as well as amino acids from lunar-sample gas mixtures under electrical discharge conditions. These results extend the possibility of synthesis of amino acids to planetary bodies with primordial atmospheres less reducing than a mixture of methane, ammonia, hydrogen and water.
J Mol Evol 1984
PMID:On the abiotic formation of amino acids. I. HCN as a precursor of amino acids detected in extracts of lunar samples. II. Formation of HCN and amino acids from simulated mixtures of gases released from lunar samples. 633 Mar 74

The supply of NADPH for cytochrome P-450-dependent mixed function oxidation from the pentose cycle and mitochondria in periportal and pericentral regions of the liver lobule was evaluated in perfused rat liver. Rates of 7-ethoxycoumarin O-deethylation in livers from fed, normal rats monitored with micro-light guides placed on periportal and pericentral regions were 1.2 mumol/g/hr in both regions of the liver lobule. In livers from fed, phenobarbital-treated rats, rates were 3.6 and 7.0 mumol/g/hr in periportal and pericentral regions, respectively. Following treatment of rats with 6-aminonicotinamide, an inhibitor of the pentose cycle, rates of 7-hydroxycoumarin production were approximately 0.9 mumol/g/hr in both regions of the lobule in livers from normal rats and 2.1 and 3.4 mumol/g/hr in periportal and pericentral regions, respectively, in livers from phenobarbital-treated rats. Based on the difference in rates of 7-hydroxycoumarin production in the presence and absence of 6-aminonicotinamide, we conclude that the pentose cycle supplies NADPH for 7-ethoxycoumarin metabolism at rates around 0.3 mumol/g/hr in both regions of the liver lobule in livers from normal rats and 1.5 and 3.6 mumol/g/hr in periportal and pericentral regions, respectively, in livers from phenobarbital-treated rats. Potassium cyanide, an inhibitor of mitochondrial oxidation, reduced rates of 7-ethoxycoumarin O-deethylation to approximately 0.6 mumol/g/hr in both regions of the liver lobule in livers from fed, normal rats and to around 0.2 mumol/g/hr after fasting or treatment with 6-aminonicotinamide. In livers from fasted, phenobarbital-treated rats, 7-hydroxycoumarin was produced at rates of 0.3 and 0.7 mumol/g/hr in periportal and pericentral regions, respectively, in the presence of KCN. Decreases in rates of 7-hydroxycoumarin production during KCN infusion indicate that the mitochondria supply about 0.7 mumol of NADPH/g/hr for 7-ethoxycoumarin metabolism in both regions in livers from normal rats and 1.3 and 2.7 mumol/g/hr in periportal and pericentral regions in livers from phenobarbital-treated rats. The sum of KCN and 6-aminonicotinamide-sensitive rates of 7-ethoxycoumarin metabolism closely approximated rates measured in the absence of the inhibitors. These data indicate that mitochondria supply 50 to 70% of the reducing equivalents for mixed function oxidation of 7-ethoxycoumarin in both regions of the liver lobule in livers from fed rats.
Mol Pharmacol 1984 Nov
PMID:Reducing equivalents for mixed function oxidation in periportal and pericentral regions of the liver lobule in perfused livers from normal and phenobarbital-treated rats. 633 82

The accumulation of calcium during myocardial hypoxia or ischaemia followed by reoxygenation or reperfusion is related to the development of cell necrosis and may be an important causal mechanism. Influx of calcium is a late event during hypoxia but occurs abruptly on reoxygenation or reperfusion. On reoxygenation calcium influx is not altered by nifedipine or quiescence but can be prevented by nickel (3 mM), cyanide (5 mM) or FCCP (10(-6) M). The extracellular marker 51Cr-EDTA does not enter the intracellular fluid on reoxygenation but can when the cell membrane is disrupted by a detergent, Brij'35, or the calcium paradox. The results suggest that the uptake of calcium on reoxygenation or reperfusion is related to the reintroduction of oxygen and caused by an increased calcium influx down the concentration gradient. The flux is not through the slow calcium channel and is not due to disruption of the membrane. The effects of CN- and FCCP and the unaltered calcium efflux suggest that the major part of the calcium uptake is stored in intracellular compartments and is not located in the intracellular fluid.
J Mol Cell Cardiol 1984 Feb
PMID:Calcium out of control. 637 Dec 54


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