Please use this identifier to cite or link to this item:
標題: Effects of structural analogues of the substrate and allosteric regulator of the human mitochondrial NAD(P)(+)-dependent malic enzyme
作者: Su, K.L.
Chang, K.Y.
Hung, H.C.
關鍵字: Allosteric activator;Inhibitor;Dicarboxylic acid;Active site;Allosteric site;cancer cell-line;ascaris-suum;functional roles;oxidative;decarboxylases;catalytic mechanism;crystal-structure;cdna cloning;site;purification;malate
Project: Bioorganic & Medicinal Chemistry
期刊/報告no:: Bioorganic & Medicinal Chemistry, Volume 17, Issue 15, Page(s) 5414-5419.
Fumarate, a four-carbon trans dicarboxylic acid, is the allosteric activator of the human mitochondrial NAD(P)(+)-dependent malic enzyme (m-NAD(P)-ME). In this paper, we discuss the effects of the structural analogues of fumarate on human m-NAD(P)-ME. Succinate, a dicarboxylic acid with a carbon-carbon single bond, can also activate the enzyme, but the activating effect of succinate is less than that of fumarate. Succinamide, a diamide of succinate, cannot activate the enzyme and is a poor active-site inhibitor. The cis isomer of fumarate, maleic acid, significantly inhibits the ME activity, suggesting that the trans configuration of fumarate is crucial for operating the allosteric regulation of the enzyme. Other dicarboxylic acids, including glutaconic acid, malonic acid and alpha-ketoglutarate, cannot activate the enzyme and inversely inhibit enzyme activity. Our data suggest that these structural analogues are mainly active-site inhibitors, although they may enter the allosteric site to inhibit the enzyme. Furthermore, these data also suggest that the dicarboxylic acid must be in a trans conformation for allosteric activation of the enzyme. (C) 2009 Elsevier Ltd. All rights reserved.
ISSN: 0968-0896
DOI: 10.1016/j.bmc.2009.06.052
Appears in Collections:生命科學系所

Show full item record

Google ScholarTM




Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.