Ca2+Mg2+ATPase

Nonsteroidal SERMs can also amplify signal-induced Ca2+ surges by inhibiting Ca2+-calmodulin-dependent membrane (Ca2+ + Mg2+)-ATPase. For instance, in synaptic plasma membranes and red cell membrane ghosts, tamoxifen and other triphenylethylene compounds (but not estradiol) have been... 

Malva JO, Lopes MCF, Vale MGP, Carvalho AP (1990) Actions of antiestrogens on the (Ca2+ + Mg2+)-ATPase and Na+/Ca2 + exchange of brain cortex membranes. Biochem Pharmacol 40 1877-1884... 

The inhibition of membrane Ca2+/Mg2+ ATPase leads to a derangement of Ca2+ levels, which will damage the mitochondria and hence also indirectly contribute to ATP depletion. Inhibition of y-glutamyl cysteine synthetase reduces the ability of the liver cell to synthesize new GSH, so reducing its ability to protect itself. Overall, some 17 enzymes have been shown to be inhibited ex vivo after treatment of animals and another 14 are known to have bound paracetamol and may or may not be inhibited. 

The best studied example of a Group IIA cation transport system is the calcium pump of the sarcoplasmic reticulum of skeletal muscle. Indeed, the calcium pump and the sodium pump represent the most studied of all transport processes. The calcium pump involves a membrane-bound (Ca2+, Mg2+)-ATPase and uptake of Ca2+ is associated with hydrolysis of ATP. While the... 

Various aspects of the (Ca2+, Mg2+)-ATPase have been reviewed.126 133 It can be isolated in vesicular form from homogenized skeletal muscle. Since it is the major protein component of SR membranes, it can also be isolated fairly easily in relatively pure form. The enzyme has a molecular weight in the range 100 000-120 000, and forms oligomers in the SR membranes, probably tetramers.133 Each subunit is associated with about 30 molecules of phospholipid, which are suggested to form a shell or annulus around the protein. The monomeric subunit has ATPase activity, and remains monomeric throughout the enzyme cycle,136 although the behaviour of the monomer is dependent on the solubilization procedure. 37... 

Trypsin hydrolysis of SR vesicles cleaves the (Ca2, Mg2+)-ATPase into three fragments, NH2-20 000, 30 000 and 45 OOO-COOH. The phosphorylation site is associated with an aspartic acid residue in the 30 000 fragment and ionophoric activity with the 20 000 fragment. The amino terminus of the enzyme is located on the cytoplasmic side of the membrane.143... 

Most mechanisms for the (Ca2+, Mg2+)-ATPase are modifications of the proposal of deMeis et a/.128 An example is shown in Figure 9. The ATPase can utilize CaATP and MgATP as substrates.147 Two moles of Ca2+ are bound per mole of the phosphorylation site with high affinity, followed by phosphorylation of the enzyme by ATP. Conformational changes in the phosphoprotein lead to the calcium sites being accessible to the intravesicular space, with decrease in their affinity for... 

A variety of other calcium transport systems are associated with Ca21-activated ATPases. The extraembryonic structure, the chorioallantoic membrane, of the chick embryo is responsible for the translocation of over 120 mg of eggshell calcium into (he embryo during development. The enzyme responsible for this is a (Ca2+, Mg2+)-ATPase with Km values for Ca2+ of 30 p,mol dm-3 and 0.3 mmol dm-3, and a molecular weight of 170 000. The enzyme can be crossiinked and co-isolated with a calcium-binding protein.158 Transport of Ca2+ is also associated with (Ca2+, Mg2+)-ATPases in neutrophil plasma membranes,159 transverse tubule membranes from rabbit skeletal muscle,160 rabbit myocardial membrane,161 endoplasmic reticulum,162 sar-colemma,163 brain microsomes,164 the Golgi apparatus165 and rat liver plasma membranes.166... 

Gould GW, Colyer J, East JM, et al. 1987. Silver ions trigger Ca2+ release by interaction with the (Ca2+-Mg2+) -ATPase. J Biol Chem 262 7676-7679. 

Mas-Oliva, J., Perez-Montfort, R., Cardenas-Garcia, M. and Rivas-Duro, M., 1991, Altered coupling states between calcium transport and (Ca2+, Mg2+)-ATPase in the AS-30D ascites hepatocarcinoma plasma membrane. Mol Cell Biochem 100, 39—50. 

Ion transport is central to nerve impulse transmission both along the axon and at the synapse and many neurotoxicants elicit effects by interfering with the normal transport of these ions (Figure 11.6). The action potential of an axon is maintained by the high concentration of sodium on the outside of the cell as compared to the low concentration inside. Active transporters of sodium (Na+K+ ATPases) that actively transport sodium out of the cell establish this action potential. One action of the insecticide DDT resulting in its acute toxicity is the inhibition of these Na+K+ ATPases resulting in the inability of the nerve to establish an action potential. Pyrethroid insecticides also elicit neurotoxicity through this mechanism. DDT also inhibits Ca2+Mg2+ ATPases, which are important to neuronal repolarization and the cessation of impulse transmission across synapses. 

Mata, A.M., Matthews, I., Tunwell, R.E.A., Sharma, R.P., Lee, A.G., East, J.M. (1992). Definition of surface-exposed and trans-membranous regions of the (Ca2+-Mg2+)-ATPase of sarcoplasmic reticulum using anti-peptide antibodies. Biochem. J. 286, 567-580. 

Glucagon causes a 30-40% inhibition of ATP-dependent Ca2+ transport activity and (Ca2+-Mg2+)-ATPase activity in liver plasma membranes [150-152]. however, much higher glucagon concentrations (0.1-10/i.M) are required to produce these changes [150-152] than to activate adenylate cyclase (0.1-100 nM), and the inhibition of the ATPase is not mimicked by cAMP or its analogues [157]. The effects of several glucagon derivatives on the ATPase are also very different from their effects on adenylate cyclase [150]. All of these observations indicate that the two effects are not related. 

The enzymes called ATP phosphohydrolase are widely distributed in the evolutionary chain and in biological systems. In some cases the ATPase is activated either by magnesium (Mg2+ ATPase) or by calcium (Ca2+ ATPase), and in other cases by both calcium and magnesium (Ca2+ Mg2+ ATPase). Another class of ATPase is stimulated by sodium and potassium and is inhibited by ouabain being denominated Na+ K+ ATPase. There are some ATPases that hydrolyze other nucleotides than ATP, however, with a high preference for ATP. 

The effect of change in ionic radius in going from La3+ to Lu3+ showed in some cases no systematic trend. While in other cases two types of trend have been observed (i) systematic increase from La3+ to Lu3+ for the activation of a-amylase [10], (ii) decrease in effect from La3+ to Lu3+ in the case of inhibition of Ca2+/Mg2+-ATPase of skeletal muscle sarcoplasmic reticulum [11],... 

CAM, Crassulacean acid metabolism CaM—Ca2+-Mg2+-ATPase, Ca2+-CaM-activated Ca2+-Mg2+-ATPase CaM—Ca2+-ATPase, Ca2+—calmodulin-dependent Ca2+-ATPase CaM-FC, Ca2+-dependent calmodulin fluorescence change... 

Edelfors S, Ravn-Jonsen A. 1992. Effect of organic solvents on nervous cell membrane as measured by changes in the (Ca2+/Mg2+) ATPase activity and fluidity of synaptosomal membrane. Pharmacol Toxicol 70 181-187... 

Lipids play an essential role in the structure and function of biological membranes. The concept that the lipid enviroment influences the activity of membrane bound enzymes is now generally accepted. The sarcoplasmic reticulum(SR) of skeletal muscle is an intracellular membranous system with an important physiological role in contraction and relaxation (Hasselbach, 1964 Martonosi, 1971). The Ca2+ transport and (Ca2++ Mg2+)-ATPase activities which exhibit isolated SR preparations have been shown to be dependent on membrane phospholipids (Martonosi, 1968). An involvement of the fatty acid component of phospholipids in the functioning of the Ca2+ pump has also been suggested (Seiler et al., 1970 Seiler Hasselbach,... 

The above described variations in Ca transport are roughly proportional to developmental changes in steady state concentration of the phosphoprotein intermediate involved in the hydrolysis of ATP by the (Ca2++Mg2+)-ATPase, which may be considered an indicator of enzyme concentration (Figure 2). The total amounts (nmoles 32p/piate) of Ca transport ATPase in cultured muscle increase between the second and the 8th day close to 20 fold (Fig. 2A). 

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