This volume disseminates the most recent advances in understanding of the molecular structure, transport mechanism, and regulatory properties of the sodium/potassium adenosine triphosphatase. Recent knowledge gained from other transport ATPases is incorporated as well. The volume also provides contributions from crystallographers, cryoelectronmicroscopists, biochemists, cell biologists, biophysicists, physiologists, and pharmacologists.
In 1997, J.C. Skou was awarded the Nobel Prize in Chemistry for his discovery of Na/K-ATPase, which has led to widespread appreciation of this enzyme in the scientific community. This volume contains the latest findings and insights in the field and acts as a reference source containing a comprehensive overview of the present state of knowledge. It includes a proposal that Na/K-ATPase plays a role as a tranducer of signal transduction, and, amongst other topics, covers the oligomericity of the enzyme, the site directed mutagenesis of P-type ATPases and the role of g-subunit. The book will serve as an important resouce, not only for work on Na/K-ATPase, but also for the investigation of other P-type ATPases.
This text focuses on research on the structure, molecular mechanisms, physiological regulation, and involvement in disease of Na, K-ATPase and other members of the family of cation pumps. Prominent members of this family include gastric H, K-ATPase, Ca-ATPase of sarcoplasmic and endoplasmic reticulum, plasma membrane Ca-ATPase, and plasma membrane of H-ATPase of fungi and higher plants, as well as heavy metal pumps. The volume includes details of the first high-resolution structure ever obtained of a P-type pump, the sarcoplasmic reticulum Ca-ATPase; this structure has great predictive power relative to all P-type pumps. There are 50 papers and 97 poster papers altogethe
The sodium of animal cell membranes converts the chemical energy obtained from the hydrolysis of adenosine 5' -triphosphate into a movement of the cations Na + and K + against an electrochemical gradient. The gradient is used subse quently as an energy source to drive the uptake of metabolic substrates in polar epithelial cells and to use it for purposes of communications in excitable cells. The biological importance of the sodium pump is evident from the fact that be tween 20-70% of the cell's metabolic energy is consumed for the pumping pro cess. Moreover, the sodium pump is an important biological system involved in regulatory processes like the maintenance of the cells' and organism's water me tabolism. It is therefore understandable that special cellular demands are han dled better by special isoforms of the sodium pump, that the expression of the sodium pump and their isoforms is regulated by hormones as is the activity of the sodium pump via hormone-regulated protein kinases. Additionally, the sodium pump itself seems to be a receptor for a putative new group of hormones, the endogenous digitalis-like substances, which still have to be defined in most cases in their structure. This group of substances has its chemically well known coun terpart in steroids from plant and toad origin which are generally known as "car diac glycosides". They are in medical use since at least 200 years in medicine in the treatment of heart diseases.
This text addresses the question, How does the sodium pump pump'. A variety of primary structure information is available, and progress has been made in the functional characterization of the Na, K-pump, making the answer to this question possible, within reach of currently used techniques
Na, K-ATPase and gastric H, K-ATPase are primary active transporters that belong to the superfamily of P-type ATPases. These membrane proteins utilize the energy released by the hydrolysis of ATP to transport their cationic substrates against electrochemical gradients. Despite more than 50 years of extensive research on P-type ATPases, the molecular details of their ion transport mechanisms are not fully understood. Especially for oligomeric P-type ATPases, such as Na, K- and H, K-ATPases, which require an accessory -subunit for their transport activity, many open questions remain, since only recently structural information became available. This thesis encompasses a comprehensive analysis of Na, K- and H, K-ATPase mutations in conserved -subunit regions and other domains that may be relevant for interactions to the respective -subunit according to the recently available structural data. Therefore, this work contributes to the understanding of how -subunits influence the transport activity of P2C-type ATPases and provides a clue to the question whether similar molecular mechanisms are responsible for this kind of cation transport modulation of the two related ion pumps.
Na+-K+ ATPase or Na-pump ATPase, a member of “P”-type ATPase superfamily, is characterized by association of multiple isoforms mainly of it’s α- and β- subunits. At present four different α- (α-1,α-2,α-3 and α-4) and three β- (β-1, β-2, and β-3) isoforms have been identified in mammalian cells and their differential expressions are tissue specific. Regulation of Na+-K+ ATPase activity is an important but a complex process, which involves short-term and long-term mechanisms. Short-term regulation of Na+-K+ ATPase is either mediated by changes in intracellular Na+ concentrations that directly affect the Na+-pump activity or by phosphorylation/dephosphorylation-mediated by some stimulants leading to changes in its expression and transport properties. On the other hand, long-term regulation of Na+-K+ ATPase is mediated by hormones, such as mineralocorticoids and thyroid hormones, which cause changes in the transcription of genes of α- and β- subunits leading to an increased expression in the level of Na+-pump. Several studies have revealed a relatively new type of regulation that involves the association of small, single span membrane proteins with this enzyme. These proteins belong to the FXYD family, the members of which share a common signature sequence encompassing the transmembra ne domain adjacent to the isoform(s) of α-β subunits of Na+-K+ ATPase. Considering the extraordinary importance of Na+-K+ ATPase in cellular function, several internationally established investigators have contributed their articles in the monograph entitled “Regulation of Membrane Na+-K+ ATPase” for inspiring young scientists and graduate students to enrich their knowledge on the enzyme, and we are sure that this book will soon be considered as a comprehensive scientific literature in the area of Na+-K+ ATPase regulation in health and disease.
