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Part-1Review on Antiulcer LiteratureR 3 R 4R 3 R 4R 2R 2NNNNSNNHSS-EnzymeR 1Figure 9: Covalent binding of sulfenamide with thiol group of proton pump.R 11.3. Structure of the Proton PumpThe gastric H + /K + -ATPase is a member of the P2-type ATPase family and undergoes acycle of phosphorylation and dephosphorylation coupled to the outward and inwardtransport of hydrogen and potassium ions, respectively, in the secretory canaliculus of theparietal cells. Conformations of the enzyme that bind ions for outward transport aredefined as E1, whereas those that bind luminal ions for inward transport are termed E2.Ion binding to E1 activates phosphorylation from MgATP to form the intermediate E1-P,which then converts to E2-P in the acid transporting step. In the gastric H + /K + -ATPase aswell as the Na + /K + -ATPases, K + binding to E2-P stimulates dephosphorylation to give theoccluded form E2•K + occ followed by conversion to E1•K + and release of K + to thecytoplasm. The gastric H + /K + -ATPase sustains a 10-fold inward potassium gradient (150K + in, 15 mM K + out) and a transmembrane outward hydrogen ion gradient of greaterthan 1 million fold to generate a luminal pH of 0.8. This is the largest ion gradientgenerated by a P2-type ATPase. The exported ions are presumed to be hydronium ratherthan protons partly because of the ability of Na + to act as a competent surrogate for H + atpH 8. Hence, there is a functional similarity to the Na + /K + -ATPase at this pH. Theprimary structure of the gastric H + /K + -ATPase (HK R1) shows significant homologyto the Na + /K + -ATPase (62%) and the sr Ca-ATPase 1 (29%). The ion binding sites of theH + /K + -ATPase are homologous to these, and other, P2-type ATPases in that they haveonly carboxylate side chains as the counter charge species.15