Calcium-activated ATPase

Other target organs for the action of 1,25-dihydroxyvitamin D include the kidneys, bone, muscle,vwand skin. The hormone promotes reabsorption of both Ca2+ and inorganic phosphate by kidney tubules. In bone it binds to a specific receptor where it promotes the mobilization of calcium ions. This effect may result in part from stimulation of calcium-activated ATPase of the outer membrane of bone cells. Dissolution of bone also requires the presence of parathyroid hormone (PTH), the 83-residue hormone secreted by the parathyroid gland. In women past the age of menopause and in elderly men the production of 1,25-dihydroxyvitamin D decreases.w This may be a cause of the serious bone loss (osteoporosis) frequently observed. Treatment with 1,25-dihydroxyvitamin D3 or a synthetic analog seems to be helpful to such individuals. /Xy See also Chapter 30, Section A,5. 

Calcium transfer observed in chick embryo may also be controlled by a similar mechanism since the newly hatched chick has six times the amount of calcium initially present in the egg yolk. In this case the egg shell is the bound Ca2+ pool. It is not clear to what extent calcium-activated ATPase or a calcium-binding protein carrier is involved in active transcellular transport of calcium277,278. ... 

Calcium-activated ATPase of the sarcoplasmic reticulum membranes... 

Chapter 7. Calcium-activated ATPase of the sarcoplasmic reticulum membranes, by W. Hasselbach... 

In addition to calcium binding protein, alkaline phosphatase activity is stimulated by 1,25-dihydroxycholecalciferol. This stimulation is inhibited by cycloheximide but not by actinomycin D or cordycepin. In fact, the latter two substances stimulate alkaline phosphatase activity (Bikle et al., 1979). Other enzymes are stimulated by 1,25-dihydroxycholecalciferol, including RNA polymerase and calcium-activated ATPase. 

Edelfors S, Raven-Jonsen A. 1992. Effect of organic solvents on nervous cell membrane as measured by changes in the calcium magnesium ATPase activity and fluidity of synaptosomal membrane. Pharmacology and Toxicology 70(3) 181-187. 

It was very early recognized that the calcium transport and the calcium-dependent ATPase could simultaneously be blocked by thiol reagents26). In contrast to various other thiol containing enzymes the activities of the sarcoplasmic reticulum membranes cannot be restored when the blocking agents are removed. 

Fig. 11. Reactivation of calcium dependent ATPase activity of lipid deprived sarcoplasmic reticulum membranes by single chain lipid...

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. 

Measurements of the steady state phosphoprotein level at different temperatures revealed that phosphoprotein formation is accompanied by a large and constant enthalpy change of 48 kJ/mol. In contrast, the likewise quite high activation energy of phosphoprotein formation exhibits a pronounced break between 20°C and 30°C. A break in the Arrhenius plot of the calcium-dependent ATPase has been observed in the same temperature range and has been interpreted as transitions between two activity states of the enzyme. Apparently, the phosphorylation of the calcium free protein by inorganic phosphate exhibits a similar kind of activity transition as observed for the calcium-dependent interaction of the transport protein with ATP131. A similar transition phenomenon complicates the time course of phosphoprotein formation... 

These polyketides, plakortides, have also been shown as potent activators of cardiac calcium-pumping ATPase [434], New cyclic polyketides were recently isolated from the Red Sea marine sponge Acarnus bergquistae [435], while cytotoxic polyketides have also been reported from sea hares of the genus Aplysia and Dolabella [436], and the marine sponge The one Ha swinhei [437],... 

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... 

Adhikari BB, Wang K. 2001. S100A1 modulates skeletal muscle contraction by desensitizing calcium activation of isometric tension, stiffness and ATPase. FEBS Lett 497(2, 3) 95-98. 

Membrane-bound enzymes, particularly the ATPases involved in the ionic pumps for calcium, sodium and potassium, have been found to function abnormally in the brains of epileptic patients and animals. A reduction in Na+K+-ATPase activity has been reported in human focal epileptogenic tissue, but it is uncertain whether such changes are due to the disease itself or a reflection of drug treatment. Similar changes have, however, been reported in experimental animals following the localized application of alumina cream and in DBA/2 mice that exhibit sound-induced seizures a reduction in calcium-dependent ATPase has also been found in the brain of DBA/2 mice. Such findings are consistent with the hypothesis that a defect in ion channels may occur in epilepsy. 

Andersson, D. A., Zygmunt, P. M., Movahed, P., Andersson, T. L., and Hogestatt, E. D. 2000. Effects of inhibitors of small- and intermediate-conductance calcium-activated potassium channels, inwardly-rectifying potassium channels and Na(+)/K(+) ATPase on EDHF relaxations in the rat hepatic artery. Br. J. Pharmacol. 129 1490-1496. 

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. 

Pumiliotoxin B has both cardiotonic and myotonic activity in isolated atrial or rat phrenic nerve diaphragm preparations (97). The cardiotonic activity is markedly dependent on the structure of the pumiliotoxin (95). Subsequent studies on the activity of pumiliotoxin B in neuromuscular preparations were interpreted as due to an apparent facilitation of calcium translocation from internal storage sites (99 see review in Ref. 5). Inhibitory effects on the calcium-dependent ATPase of sarcoplasmic reticulum were shown to be due not to pumiliotoxin B, but to phenolic impurities, namely, fcis(2-hydroxy-3-terf-butyl-5-methylphenyl)methane, 3,5-di-/ert-butyl-4-hydroxytoluene (BHT), and nonylphenols (100). 

---