The Inhibition of Fumarase and Malic Dehydrogenase

The competitive inhibition of malic dehydrogenase by /3-fluorooxaloacetate has been reported by Kun et al. (1). In addition to its inhibitory effect, /3-fluoro-oxaloacetate also oxidized reduced diphosphopyridine nucleotide enzymatically, but at a rate only 0.02% that of oxaloacetate. It was also shown (2) that fi-fluorooxaloacetate was a competitive inhibitor of glutamic-aspartic transaminase, and when tested as a substrate, it was transaminated at one-thirtieth the rate of oxaloacetate. Taylor and Kent (3) prepared disodium @fluoromalate by the alkaline hydrolysis of dimethyl /3-fluoromalate. This product inhibited the malic enzyme and diand triphosphopyridine nucleotide-dependent malic dehydrogenase, but did not inhibit crystalline fumarase (4). Callely and Dagley (5) found that in the presence of /3-fluoromalate, a vibrio accumulated pyruvic acid when grown on malate. The oxidations of pyruvate, malate, fumarate, and succinate were inhibited in the presence of fl-fluoromalate. This paper describes the synthesis in pure form of two isomers of nr&fluoromalic acid and the inhibition of malic dehydrogenase and fumarase by one of these isomers.