title: Covalent and non-covalent inhibitors of the phosphate transporter of sarcoplasmic reticulum.
abstract: The sarcoplasmic reticulum (SR) of skeletal muscle contains a Pi transporter which transports Pi into the lumen of the SR, increasing the level of accumulation of Ca2+ by SR by forming insoluble salts with Ca2+. Phosphonocarboxylic acids inhibit the transport of Pi by the transporter, phosphonoformic acid itself being transported into the SR increasing the level of accumulation of Ca2+. Phenylphosphonic acid also inhibits Pi transport, distinguishing the Pi transporter of SR from the Na+/Pi transporter of brush-border membranes. Oxalate transport is also inhibited by the phosphono-carboxylic acids, consistent with the suggestion that oxalate and phosphate are carried on the same transporter. The effects of maleate are, however, not inhibited, suggesting a separate carrier for the dicarboxylic acids. Acetic anhydride and phenylglyoxal inhibit the transporter, Pi providing protection against the effects of acetic anhydride, suggesting the presence of a lysine residue at the Pi binding site. ATP provides protection against the effects of acetic anhydride and phenylglyoxal, suggesting the presence of an ATP binding site on the transporter.
authors.affiliation: Department of Biochemistry, University of Southampton, U.K.
authors.forename: H I
authors.initials: HI
authors.lastname: Stefanova
authors.forename: J M
authors.initials: JM
authors.lastname: East
authors.forename: A G
authors.initials: AG
authors.lastname: Lee
mesh_terms: D000089:Acetic Anhydrides / Q000494:pharmacology*; D000251:Adenosine Triphosphatases / Q000378:metabolism; D000818:Animals; D001665:Binding Sites; D001692:Biological Transport; D002118:Calcium / Q000378:metabolism; D002352:Carrier Proteins / Q000378:metabolism*; D005260:Female; D017245:Foscarnet; D008298:Maleates / Q000378:metabolism; D008565:Membrane Proteins / Q000378:metabolism*; D009132:Muscles / Q000187:drug effects / Q000378:metabolism; D010658:Phenylglyoxal / Q000494:pharmacology*; D028044:Phosphate-Binding Proteins; D010710:Phosphates / Q000378:metabolism*; D010746:Phosphonoacetic Acid / Q000031:analogs & derivatives / Q000378:metabolism; D011817:Rabbits; D012519:Sarcoplasmic Reticulum / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism*; D013386:Succinates / Q000378:metabolism; D019802:Succinic Acid
chemical_list: D000089:Acetic Anhydrides; D002352:Carrier Proteins; D008298:Maleates; D008565:Membrane Proteins; D028044:Phosphate-Binding Proteins; D010710:Phosphates; D013386:Succinates; C031800:acetic anhydride; D017245:Foscarnet; C030272:maleic acid; D019802:Succinic Acid; D000251:Adenosine Triphosphatases; D010658:Phenylglyoxal; D010746:Phosphonoacetic Acid; D002118:Calcium