The sarcoplasmic Ca2+-ATPase: design of a perfect chemi-osmotic pump.
Summary of "The sarcoplasmic Ca2+-ATPase: design of a perfect chemi-osmotic pump."
The sarcoplasmic (SERCA 1a) Ca2+-ATPase is a membrane protein abundantly present in skeletal mucles where it functions as an indispensable component of the excitation-contraction coupling, being at the expense of ATP hydrolysis involved in Ca2+/H+ exchange with a high thermodynamic efficiency across the sarcoplasmic reticulum membrane. The transporter serves as a prototype of a whole family of cation transporters, the P-type ATPases, which in addition to Ca2+ transporting proteins count Na+, K+-ATPase and H+, K+-, proton- and heavy metal transporting ATPases as prominent members. The ability in recent years to produce and analyze at atomic (2.3-3 A) resolution 3D-crystals of Ca2+-transport intermediates of SERCA 1a has meant a breakthrough in our understanding of the structural aspects of the transport mechanism. We describe here the detailed construction of the ATPase in terms of one membraneous and three cytosolic domains held together by a central core that mediates coupling between Ca2+-transport and ATP hydrolysis. During turnover, the pump is present in two different conformational states, E1 and E2, with a preference for the binding of Ca2+ and H+, respectively. We discuss how phosphorylated and non-phosphorylated forms of these conformational states with cytosolic, occluded or luminally exposed cation-binding sites are able to convert the chemical energy derived from ATP hydrolysis into an electrochemical gradient of Ca2+ across the sarcoplasmic reticulum membrane. In conjunction with these basic reactions which serve as a structural framework for the transport function of other P-type ATPases as well, we also review the role of the lipid phase and the regulatory and thermodynamic aspects of the transport mechanism.
Centre for Membrane Pumps in Cells and Disease - PUMPKIN, Danish National Research Foundation, Denmark.
This article was published in the following journal.
Name: Quarterly reviews of biophysics
- PubMed Source: http://www.ncbi.nlm.nih.gov/pubmed/20809990
- DOI: http://dx.doi.org/10.1017/S003358351000017X
This article offers an explanation for the apparent lack of Na, K-ATPase activity in parietal cells although ouabain has been known to inhibit gastric acid secretion since 1962. The gastric H, K-ATPas...
Vacuolar ATPases (v-ATPases) hydrolyze adenosine triphospate (ATP) to pump protons across cell membranes. Mutations in v-ATPase subunits are implicated in three human disorders: distal renal tubular a...
Abstract Preparation and in vitro/in vivo evaluation of risperidone elementary osmotic pump (RIS-EOP) formulations were investigated. A method for the preparation of RIS-EOP tablets was developed by m...
The ATP4A encodes α subunit of H(+), K(+)-ATPase that contains catalytic sites of the enzyme forming pores through cell membrane which allows the ion transport. H(+), K(+)-ATPase is a membrane bound...
Purpose: Children requiring artificial heart-lung support through extracorporeal membrane oxygenation (ECMO) are at increased risk of developing acute kidney injury (AKI). Continuous renal replacement...
Recently literature revealed facts, that show H+/K+ ATPase expression is not limited tot he stomach. H+/K+ ATPase was also found in smooth muscle cells and in other tissues (McCabe, R.D. e...
The purpose of this study is to measure colloid osmotic pressure in interstitial fluid and plasma in healthy children under two years, in asphyxiated babies and in children undergoing hear...
One the day prior to medical abortion (labor induction) in the second trimester, insertion of osmotic dilators is added to the routine procedures. The study is to see whether the addition...
The purpose of this study is to identify normal values of colloid osmotic pressure in interstitial fluid and plasma in healthy children between 2 and 10 years.
The purpose is to evaluate the clinical efficacy of Hydromorphone HCl ORal Osmotic System by assessing the degree of reduction of medication frequency for the management of breakthrough pa...
Medical and Biotech [MESH] Definitions
A highly effective inhibitor of gastric acid secretion used in the therapy of STOMACH ULCERS and ZOLLINGER-ELLISON SYNDROME. The drug inhibits the H(+)-K(+)-ATPase (H(+)-K(+)-EXCHANGING ATPASE) in the proton pump of GASTRIC PARIETAL CELLS.
A methylpyrrole-carboxylate from RYANIA that disrupts the RYANODINE RECEPTOR CALCIUM RELEASE CHANNEL to modify CALCIUM release from SARCOPLASMIC RETICULUM resulting in alteration of MUSCLE CONTRACTION. It was previously used in INSECTICIDES. It is used experimentally in conjunction with THAPSIGARGIN and other inhibitors of CALCIUM ATPASE uptake of calcium into SARCOPLASMIC RETICULUM.
A sesquiterpene lactone found in roots of THAPSIA. It inhibits CA(2+)-TRANSPORTING ATPASE mediated uptake of CALCIUM into SARCOPLASMIC RETICULUM.
Compounds that inhibit H(+)-K(+)-EXCHANGING ATPASE. They are used as ANTI-ULCER AGENTS and sometimes in place of HISTAMINE H2 ANTAGONISTS for GASTROESOPHAGEAL REFLUX.
Compounds that contain benzimidazole joined to a 2-methylpyridine via a sulfoxide linkage. Several of the compounds in this class are ANTI-ULCER AGENTS that act by inhibiting the POTASSIUM HYDROGEN ATPASE found in the PROTON PUMP of GASTRIC PARIETAL CELLS.