Inhibition of fumarase by S-2,3-dicarboxyaziridine

S-2,3-Dicarboxyaziridine was found to be a potent competitive inhibitor (Ki = 0.08 microM) of fumarase from pig heart. The aziridine did not inactivate the enzyme or exhibit any observable substrate activity. It is likely that it functions as a transition state analogue mimicking the carbanion intermediate found in the normal catalytic reaction. The aziridine inhibited fumarate utilization in ruptured but not intact mitochondria.