Calcium ion pump

Figure 2. Schematic representation of the steps occurring during calcium ion pumping by the calcium-dependent ATPase.

Other active transport systems include the sodium-hydrogen ion pump of the Gl tract (stomach) and the calcium ion pump which helps to maintain a low concentration of calcium in the cytosol. 

A gradient in [Ca2+] of 103 or more is maintained across membranes by the calcium ion pump (Chapter 8). The action of this pump is counteracted by a very slow diffusion of the external Ca2+ back through the membrane via an Na+-Ca2+ exchange into the cells.8... 

Toyoshima, C., Sasabe, H., Stokes, D.L. (1993). Three-dimensional cryo-electron microscopy of the calcium ion pump in the sarcoplasmic reticulum membrane. Nature (London) 362,469-471. 

Contraction of muscle follows an increase of Ca " in the muscle cell as a result of nerve stimulation. This initiates processes which cause the proteins myosin and actin to be drawn together making the cell shorter and thicker. The return of the Ca " to its storage site, the sarcoplasmic reticulum, by an active pump mechanism allows the contracted muscle to relax (27). Calcium ion, also a factor in the release of acetylcholine on stimulation of nerve cells, influences the permeabiUty of cell membranes activates enzymes, such as adenosine triphosphatase (ATPase), Hpase, and some proteolytic enzymes and facihtates intestinal absorption of vitamin B 2 [68-19-9] (28). 

Interaction of the food with the gastric mucosal layer is the normal trigger for gastric cells to release gastrin, which is then carried by the bloodstream to the parietal cells. Calcium ions and cyclic AMP act as intracellular messengers in the transfer of the signal from the receptors to the proton pumps of parietal cells where the acid is generated. 

Calcium ions are actively pumped back into the extracellular fluid as well as the sarcoplasmic reticulum. When the concentration of calcium falls below... 

The binding of calcium ion to calmodulin, a major biochemical regulator of ion pumps and receptors, occurs on a time scale about a thousand times shorter than that observed for RNA conformational change. This Ca2+-calmodulin binding, which can be followed successfully by nuclear magnetic resonance (NMR), occurs in about ten milliseconds. 

ATP-dependent Ca2+ pumps and Na+,Ca2+ antiporters act in concert to maintain a low concentration of free cytosolic Ca2+. The concentration of cytosolic free calcium ion, [Ca2+] , in unstimulated cells is between 10 8 and 1 O 7 mol/1, which is more than 10,000-fold lower than extracellular free Ca2+. Most intracellular Ca2+ is stored in... 

The endoplasmic reticulum (ER) is responsible for the production of the protein and lipid components of most of the cell s organelles. The ER contains a large number of folds, but the membrane forms a single sheet enclosing a single closed sac. This internal space is called the ER lumen. The smooth endoplasmic reticulum (ER) in muscle cells contains the vesicles and tubules that serve as a store of calcium ions. These are released as one step in the muscle contraction process. Calcium pumps, Ca +-ATPases, serve to move the calcium from the cytoplasm to the ER or SR lumen. 

Calcium effects. The biochemical effects of Ca "" in the cytoplasm are mediated by special Ca -binding proteins calcium sensors"). These include the annexins, calmodulin, and troponin C in muscle (see p. 334). Calmodulin is a relatively small protein (17 kDa) that occurs in all animal cells. Binding of four Ca "" ions (light blue) converts it into a regulatory element. Via a dramatic conformational change (cf 2a and 2b), Ca -calmodulin enters into interaction with other proteins and modulates their properties. Using this mechanism, Ca "" ions regulate the activity of enzymes, ion pumps, and components of the cytoskeleton. 

Upon binding calcium ions, the small acidic protein known as calmodulin can activate enzymes by binding to a wide variety of proteins containing cahnodulin-binding domains. Such proteins include cAMP phosphodiesterase, calmodulin-dependent nitric oxide synthase, calmodulin kinases, the plasma membrane calcium pump, calcineurin, and calmodulin-dependent inositol-(l,4,5)-trisphosphate 3-kinase. See also Activation Autoinhibition... 

In both schemes, the specificities of the pump for catalysis change in the two enzyme states. Jencks points out that coupling is determined (a) by the chemical specificity achieved in catalyzing phosphoryl transfer to and from the enzyme (wherein E-Ca2 reversibly binds ATP, and E reacts reversibly with orthophosphate), and (b) by the vectorial specificity for ion binding and dissociation (wherein E reversibly binds/dissociates cytoplasmic calcium ion, and E—P reversibly binds/dissociates luminal calcium). There must be a single conformation change during the reaction cycle between Ei and E2 in the free enzyme and from Ei P-Ca2 to E2-P-Ca2 after enzyme phosphorylation. 

Sodium and potassium are not the only ions which can participate in pumps and channels. Calcium is also pumped, channeled, exhanged,and stored. See Figure 23. Calcium concentration within the cell cytoplasm is very low. This allows the calcium to play a pivotal role in cellular activity. The cytoplasmic protein calmodulin binds and stores calcium ion. Various intracellular structures and organelles such as the mitochondria and sarcoplasmic reticulum also store calcium. Calcium is vital to such functions as the release of neurotransmitters from nerve cells. There are at least seven known modes of biochemical action for this ion, one of the most important of which involves stimulation of cardiac muscle protein (actin-myosin). Certain types of angina (heart pain) are believed to be caused by abnormal stimulation of cardiac arteries and muscle (coronary spasm) A relatively new class of drugs, known as the calcium channel blockers, has brought relief from pain and arrhythmias (irregular heart beats). 

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