Magnesium dependent ATPase

P-gp associated ATPase is vanadate sensitive. A membrane product prepared from baculovirus infected insect cells containing this activity is now commercially available from Gentest Corp. (Woburn, Massachusetts, U.S.). Substrates of P-gp, such as verapamil, have been demonstrated to stimulate this vanadate-sensitive membrane ATPase (123). By determination of inorganic phosphate liberated in the reaction containing a P-gp preparation and a test compound, in the presence and absence of vanadate, one can determine if the test compound is a substrate/inhibitor of P-gp (123,422). Any compound that binds to P-gp would stimulate the magnesium-dependent ATPase, and thus, this method cannot distinguish between a substrate and inhibitor of P-gp. 

Calcium plays a vitally important part in possibly as many as three sequences of the contraction—relaxation cycle of vertebrate muscle (Taylor, Lymn and Moll, 1970). In the sarcoplasmic reticulum, calcium is stored in calsequestrin, a protein which holds, with high affinity, 43 atoms of calcium per molecule. The calcium is released in response to nervous impulses and triggers a sequence of reactions that lead to contraction of the muscle. After the contraction, the calcium is pumped back into this reticulum by the calcium/magnesium-dependent ATPase. 

A number of factors have been suspected in calcium transport ionic exchange, a calcium sensitive ATPase, a calcium binding protein, vitamin D, parathormone, cortisone. Calcium uptake is depressed by sodium and enhanced if one-third of the sodium is replaced by mannitol. It appears that sodium is not required for calcium uptake or transepithelial transfer. The intestinal brush border contains a calcium-sensitive magnesium dependent ATPase. In contrast to the K, Na" ATPase, the enzyme is not inhibited by ouabain. Vitamin D induces its appearance. The exact role of the ATPase remains unresolved. 

The microsomal fraction contained a magnesium-dependent ATPase different from all other ATPases. The enzyme was not stimulated by Na or by HCOf, nor was it inhibited by ouabain or SCN". Instead, it was stimulated by K, and it was always described as the K -stimulated ATPase. The microsomes also catalyzed the hydrolysis of / nitrophenylphosphate, and because that activity was easier to measure than ATPase activity, purification of the fragments was often followed by the former rather than by the latter catalytic power. Some thought the catalysis of the two substrates was the property of one enzyme. ... 

In binding experiments, the affinity of magnesium ADP to native membranes and to the isolated calcium dependent ATPase was found to be considerably lower than that of magnesium ATP173. On the other hand, from the inhibition of the calcium-dependent ATPase or the activation of calcium release and ATP synthesis apparent affinities for ADP are obtained that are very similar to those of ATP (Fig. 12). The affinity of ADP for the enzyme apparently depends on its functional state. The affinity of ADP for the membranes under conditions of calcium release depends markedly on the pH of the medium. When the medium pH is reduced from 7.0 to 6.0, the affinity drops by a factor of 10. At pH 7.0 the affinity of the membrane for ADP corresponds to the affinity for ATP to the high affinity binding sites in the forward running mode of the pump. In contrast to the complex dependence of the forward reaction on the concentration of ATP, the dependence of the reverse reaction on ADP seems to follow simple Michaelis-Menten kinetics. 

Long-term side effects of lithium treatment include weight gain. The treatment is associated with development of hypothyroidism in about 10-15% of cases. There is an association with kidney disease. Birch has expressed the general view that Li may interact with magnesium-dependent processes, and theoretical chemistry supports this view. Despite the widespread clinical significance of Li, there is presently no consensus on its mode of action. One postulate for the mechanism is termed hyperpolarization . Li affects the conductivity in cell transport channels. Other explanations include modulation of neurotransmitter concentrations and inhibition of Na+/K+/Mg2+/ Ca2+ ATPases. 

Parietal cells contain a proton pump, the H+K+-ATPase, located in the plasma membranes of the canaliculi (canahculi folding increases the surface area for secretion of acid). This ATPase is magnesium-dependent and is not inhibited by ouabain (which distinguishes it from the Na K -ATPase). 

ATP is cleaved by most sarcoplasmic reticulum preparations at low rates in the absence of calcium ions. This activity has been denoted as basal activity [20]. When calcium accumulation is initiated, ATP is rapidly hydrolyzed in a calcium-dependent activity, reaching its optimum at a calcium concentration of 10 jaM, and which is severely suppressed by the rising calcium concentrations in the interior of the vesicles [45,64,65]. The calcium-dependent activity was early characterized as the activity of an enzyme distinctly different from the calcium-independent enzyme. In contrast to the calcium-dependent ATPase, the calcium-independent enzyme is quite insensitive to thiol or amino group reagents. Conversely, the calcium-independent activity can be abolished by low concentrations of detergents which do not reduce the activity of the calcium-dependent enzyme [66]. The two enzymatic activities further differ in their nucleotide specificity and affinity, as well as in their magnesium and temperature dependences. The basal activity most likely originates from plasmalemma and T-tubules membranes [41]. 

Magnesium Poorly understood interacts with Na+,K+ ATPase, K+ and Ca2+ channels Normalizes or increases plasma Mg2+ Torsade de pointes digitalis-induced arrhythmias IV duration dependent on dosage Toxicity Muscle weakness in overdose... 

The question for the nutritionist and clinician is Which Mg-dependent function is most sensitive to depletion of the body s magnesium and to hypomagnesemia The answer is probably ion transport systems, such as the calcium pump and Np,K-ATPase. The impaired activity of these ion pumps is likely to be responsible for the neuromuscular problems that present with an Mg deficiency. The defects would involve a difficulty in maintaining the normal movements of calcium, sodium, and potassium ions required for nerve conduction and muscle contraction,... 

Magnesium has been shown to affect the conduction of both sodium and potassium in the heart, which may be due, at least in part, to the dependence of cardiac adenosinetriphosphatase (ATPase) on magnesium. It also competes with calcium and thus decreases calcium conductance across the cardiac membranes, resulting in a prolongation of phase II of the cardiac action potential. Given intravenously, it has been shown to decrease digitalis-induced arrhythmias and torsades de pointes in susceptible patients, as well as arrhythmias produced by myocardial ischemia (e.g., due to infarction). 

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