Transport calcium sites

Schematic diagram of a cardiac muscle sarcomere, with sites of action of several drugs that alter contractility (numbered structures). Site 1 is Na+/K+ ATPase, the sodium pump. Site 2 is the sodium/calcium exchanger. Site 3 is the voltage-gated calcium channel. Site 4 is a calcium transporter that pumps calcium into the sarcoplasmic reticulum (SR). Site 5 is a calcium channel in the membrane of the SR that is triggered to release stored calcium by activator calcium. Site 6 is the actin-troponin-tropomyosin complex at which activator calcium brings about the contractile interaction of actin and myosin.

B. Phosphate ion binds the active site on calcium transporters in the intestine, inhibiting their ability to transport calcium. 

These reactions are thermodynamically unfavorable at temperatures below ca 1500°C. However, at temperatures in the range from 1000 to 1200°C a small but finite equiUbrium pressure of barium vapor is formed at the reaction site. By means of a vacuum pump, the barium vapor can be transported to a cooled region of the reactor where condensation takes place. This destroys the equiUbrium at the reaction site and allows more barium vapor to be formed. The process is completely analogous to that used in the thermal reduction of CaO with aluminum to produce metallic calcium (see Calcium AND CALCIUM alloys). 

The NHR contains also the conserved Calcineurin docking site, PxlxIT, required for the physical interaction of NEAT and Calcineurin. Dephosphorylation of at least 13 serines residues in the NHR induces a conformational change that exposes the nuclear localization sequences (NLS), allowing the nuclear translocation of NEAT. Rephosphorylation of these residues unmasks the nuclear export sequences that direct transport back to the cytoplasm. Engagement of receptors such as the antigen receptors in T and B cells is coupled to phospholipase C activation and subsequent production of inositol triphosphate. Increased levels of inositol triphosphate lead to the initial release of intracellular stores of calcium. This early increase of calcium induces opening of the plasma membrane calcium-released-activated-calcium (CRAC) channels,... 

The powerful inhibition of Ca " transport without inhibition of ATPase activity seen with polyclonal anti-ATPase sera in earlier studies [305] was probably due to complement dependent lesion of the membrane that permitted the leakage of accumulated calcium [306-308], The scarcity of inhibitory antibodies may imply that the active site of the Ca - ATPase is either inaccessible to antibodies or poorly antigenic, perhaps due to a unique secondary structure. 

One day in the spring of 1937, Dr. ter Meer and Dr. Ambros began the search for another buna site that was to take them, four years later, to Auschwitz. The prosecution contended that the "possible war" turned their feet toward the East. Only one buna plant was in the Rhine Valley, which offered everything they needed water power, calcium deposits, economy of operation. In and beside the Rhine River were water and rail transportation to take the finished rubber to its nearby destinations. 

The sodium and calcium pumps can be isolated to near purity and still exhibit most of the biochemical properties of the native pump. Some kinetic properties of these pumps in native membranes are altered or disappear as membrane preparations are purified. For example, when measured in intact membranes, the time-dependencies of phosphorylation and dephosphorylation of the pump catalytic sites exhibit biphasic fast to slow rate transition this characteristic progressively disappears as the membranes are treated with mild detergents. One suggested explanation is that, as the pumps begin to cycle, the catalytic subunits associate into higher oligomers that may permit more efficient transfer of the energy from ATP into the ion transport process [29, 30], Some structural evidence indicates that Na,K pumps exist in cell membranes as multimers of (a 3)2 [31]. 

The sequence of events that result in neurotransmission of information from one nerve cell to another across the s)mapses begins with a wave of depolarization which passes down the axon and results in the opening of the voltage-sensitive calcium charmels in the axonal terminal. These charmels are frequently concentrated in areas which correspond to the active sites of neurotransmitter release. A large (up to 100 M) but brief rise in the calcium concentration within the nerve terminal triggers the movement of the synaptic vesicles, which contain the neurotransmitter, towards the synaptic membrane. By means of specific membrane-bound proteins (such as synaptobrevin from the neuronal membrane and synaptotagrin from the vesicular membrane) the vesicles fuse with the neuronal membrane and release their contents into the synaptic gap by a process of exocytosis. Once released of their contents, the vesicle membrane is reformed and recycled within the neuronal terminal. This process is completed once the vesicles have accumulated more neurotransmitter by means of an energy-dependent transporter on the vesicle membrane (Table 2.3). 

D. Increased Na+ excretion is a direct consequence of diuretic treatment. In thick ascending limbs, the site of furosemide action, calcium and magnesium transport is largely determined by the magnitude of... 

Vitamin D3 is transported to liver where it undergoes a hydroxylation at C-25 into 1a,25-dihydroxyvitamin D3 (calcitriol) (Fig. 64). In the kidney, it undergoes further hydroxylations at different sites, depending on the serum Ca + concentration. The most biologically active metabolite of vitamin D3 is calcitriol, which plays important roles in the regulation of calcium and phosphorus metabolism. It is used for treating bone diseases, but is also involved in the cell proliferation and the inducement of cell differentiation [151]. 

Local anesthetics have poorly understood effects on inflammation at sites of injury, and these anti-inflammatory effects may contribute to improved pain control in some chronic pain syndromes. At the concentrations used in spinal anesthesia, local anesthetics can inhibit transmission via substance P (neurokinin-1), NMDA, and AMPA receptors in the secondary afferent neurons (Figure 26-1). These effects may contribute to the analgesia achieved by subarachnoid administration. Local anesthetics can also be shown to block a variety of other ion channels, including nicotinic acetylcholine channels in the spinal cord. However, there is no convincing evidence that this mechanism is important in the acute clinical effects of these drugs. High concentrations of local anesthetics in the subarachnoid space can interfere with intra-axonal transport and calcium homeostasis, contributing to potential spinal toxicity. 

In other enzymes such pockets are thought to be the sites for nucleotide binding142. A completely different type of agents which reversibly affect the calcium transport and calcium-dependent ATP splitting are substances like dimethylsulfoxid and ethyleneglycol143. They do not interfere with ATP binding as chaotropic anions do. 

Calcium ions are bound with an identical high affinity of 5.106M by the purified ATPase, by the transport protein in the native membranes as well as by partially deli-pidated, reversibly inactivated membrane preparations"8, ll9 173). The amount of calcium which is bound with that high affinity corresponds to two sites per transport molecule. The observed affinity is in good agreement with the affinity derived from the dependence on ionized calcium of the activation of calcium uptake and ATP splitting as well as of the inhibition of calcium release and ATP synthesis18 u2,, 74 17s Since the latter experiments were performed under conditions which provide a constant internal free calcium concentration by the presence of oxalate or phosphate in the system, the reactions must have been activated or inhibited by the calcium ions... 

It has been known for many years that the mitochondrion shows a respiration-linked transport of a number of ions. Of these, calcium has attracted the most attention since it depends on a specific transport system with high-affinity binding sites. The uptake of calcium usually also involves a permeant anion, but in the absence of this, protons are ejected as the electron transfer system operates. The result is either the accumulation of calcium salts in the mitochondrial matrix or an alkalinization of the interior of the mitochondrion. The transfer of calcium inwards stimulates oxygen utilization but provides an alternative to the oxidative phosphorylation of ADP618 ... 

The retardation of subsurface transport of TNT arises from this compound s absorption into NOM and adsorption onto mineral siloxane surfaces covered with weakly hydrated cations like potassium (but not sodium and calcium). While components of feldspars exhibit some siloxane surfaces, here we anticipate that most of the silox-anes occur in the aluminosilicate clay minerals (e.g., illite) because these particles have such high specific surface areas (Table 11.3). Hence, the total for TNT may be found at this site ... 

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