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肌浆网磷酸转运体的共价和非共价抑制剂。

Covalent and non-covalent inhibitors of the phosphate transporter of sarcoplasmic reticulum.

作者信息

Stefanova H I, East J M, Lee A G

机构信息

Department of Biochemistry, University of Southampton, U.K.

出版信息

Biochim Biophys Acta. 1991 May 7;1064(2):321-8. doi: 10.1016/0005-2736(91)90318-3.

DOI:10.1016/0005-2736(91)90318-3
PMID:1827996
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.

摘要

骨骼肌的肌浆网(SR)含有一种磷酸转运体,该转运体将磷酸转运到肌浆网腔中,通过与钙离子形成不溶性盐来增加肌浆网对钙离子的积累水平。膦酰基羧酸抑制该转运体对磷酸的转运,膦甲酸本身被转运到肌浆网中,从而增加了钙离子的积累水平。苯膦酸也抑制磷酸转运,这将肌浆网的磷酸转运体与刷状缘膜的钠/磷酸转运体区分开来。草酸盐的转运也受到膦酰基羧酸的抑制,这与草酸盐和磷酸盐由同一转运体转运的观点一致。然而,马来酸盐的作用未受抑制,这表明二羧酸有一个单独的载体。乙酸酐和苯乙二醛抑制该转运体,磷酸可提供对乙酸酐作用的保护,这表明在磷酸结合位点存在一个赖氨酸残基。ATP可提供对乙酸酐和苯乙二醛作用的保护,这表明该转运体上存在一个ATP结合位点。

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