6-PHOSPHOGLUCONATE DEHYDROGENASE FROM TRYPANOSOMA-BRUCEI - KINETIC-ANALYSIS AND INHIBITION BY TRYPANOCIDAL DRUGS

The kinetics of 6-phosphogluconate dehydrogenase from Trypanosoma bruc ei was examined and compared to those of the same enzyme from lamb's l iver. Variation of kinetic parameters as a function of pH suggests a c hemical mechanism similar to other 6-phosphogluconate dehydrogenases. The comparison extended to a detailed analysis of the effect on enzyme activity by several inhibitors including the trypanocidal drugs suram in, melarsoprol and analogues of these compounds. The T. brucei enzyme differs significantly from its mammalian counterpart with respect to several inhibitors, particularly the substrate analogue 6-phospho-2-de oxygluconate and the coenzyme analogue adenosine 2',5'-bisphosphate wh ich have respectively 170-fold and 40-fold higher affinity for the par asite enzyme.