Kinetics of Malic Dehydrogenase Inhibition by 2,4-Dichlorophenoxyacetic Acid

Abstract

A malic dehydrogenase isolated from beet root mitochondria was purified 100-fold, some of its characteristics determined, and the purified preparation used in a study of the kinetics of the inhibition by 2,4-D of malate oxidation and oxaloacetate reduction and the associated oxidation-reduction of diphosphopyridine nucleotide. It was found that 2,4-D inhibits the reaction catalyzed by malic dehydrogenase proceeding in either direction. This inhibition was shown to be competitive for DPN or reduced DPN and non-competitive with malate or oxaloacetate. A kinetic investigation of the mechanism of this inhibition indicates that the probable mechanism is through a non-enzymic complexing of 2,4-D with pyridine nucleotide, and that the complex so formed is an inhibitor for the enzyme. Several structurally similar compounds of the phenoxy acid and phenol types were also found to cause a competitive inhibition of malic dehydrogenase. The number and type of substituents appear to be major factors in increasing the inhibitory effectiveness of these compounds. The relation of these phenomena to the phytotoxic and growth promoting effects of 2,4-D is discussed.