MECHANISM-BASED INHIBITION OF PROLINE DEHYDROGENASE BY PROLINE ANALOGS

The inactivation of proline dehydrogenase by several L-Pro analogues w as investigated with the aim to block the essential metabolic pathway of tsetse flies allowing the degradation Of L-Pro to L-Glu. In vitro s tudies on rat liver mitochondria showed that only 4-methylene-L-prolin e was able to inactivate proline dehydrogenase. The inactivation kinet ics agreed with a mechanism-based inhibition. The other tested analogu es E- and Z-4-fluoromethylene-L-proline, and cis and trans-5-ethynyl-D ,L-proline were neither substrate nor inactivator of the enzyme. In vi vo 4-methylene-L-proline showed no toxicity against Drosophila flies, but was lethal for Glossina pallidipes flies. This result allows the c onsideration of 4-methylene-L-proline as an attractive compound molecu le in the struggle against tsetse flies.