Publication | Closed Access
Studies with specific enzyme inhibitors. XIV. The effects of enzymatically synthesized (-)-erythro-fluoromalic acid on malate dehydrogenase and on anion carriers of liver mitochondria.
14
Citations
0
References
1972
Year
EngineeringEnzymatic SynthesisMitochondrial BiologyRedox BiologyOxidative StressBiosynthesisMitochondrial BiogenesisMitochondrial StructureLiver MitochondriaAlcohol DehydrogenasesInhibitory ActivitySpecific Enzyme InhibitorsAldehyde DehydrogenaseBiochemistryMitochondrial DynamicPharmacologyBiomolecular EngineeringMetabolic PathwaysMitochondrial FunctionMalate DehydrogenaseMetabolismMedicineMalate CarrierCarbonyl Metabolism
Enzymatic synthesis and isolation of fluoromalate with a tentatively assigned (-)-erythro configuration is described. Fluoromalate inhibits purified malate dehydrogenase (Ki = 13 or 16 µM) but has no effect on the oxidation of pyruvate and succinate by liver mitochondria, indicating that fluoromalate does not penetrate the inner mitochondrial membrane. Oxidation of externally added L-malate is reversibly inhibited by fluoromalate when the latter is present at higher concentrations than malate. Oxidation of tricarboxylic acids and of α-ketoglutarate is greatly increased under state 3 conditions by fluoromalate. The rate of citrate-isocitrate translocation in mitochondria is activated by fluoromalate to the same extent as the metabolism of tricarboxylic acids. It is concluded that fluoromalate competitively inhibits the malate carrier and activates the carriers of tricarboxylic acids and of α-ketoglutarate.