6-Phosphogluconate dehydrogenase from Trypanosoma brucei. Kinetic analysis and inhibition by trypanocidal drugs.
The kinetics of 6-phosphogluconate dehydrogenase from Trypanosoma brucei was examined and compared to those of the same enzyme from lamb's liver. Variation of kinetic parameters as a function of pH suggests a chemical 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 suramin, 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-deoxygluconate and the coenzyme analogue adenosine 2',5'-bisphosphate which have respectively 170-fold and 40-fold higher affinity for the parasite enzyme.
Hanau
S
S
Dipartimento di Biochimica e Biologia molecolare, Università di Ferrara, Italy.
Rippa
M
M
Bertelli
M
M
Dallocchio
F
F
Barrett
M P
MP
D000818:Animals; D001152:Arsenicals / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D006863:Hydrogen-Ion Concentration; D007700:Kinetics; D008099:Liver / Q000201:enzymology; D008549:Melarsoprol / Q000494:pharmacology; D010734:Phosphogluconate Dehydrogenase / Q000037:antagonists & inhibitors* / Q000378:metabolism*; D012756:Sheep; D013045:Species Specificity; D013498:Suramin / Q000031:analogs & derivatives / Q000494:pharmacology; D014344:Trypanocidal Agents / Q000494:pharmacology*; D014346:Trypanosoma brucei brucei / Q000201:enzymology*
D001152:Arsenicals; D004791:Enzyme Inhibitors; D014344:Trypanocidal Agents; D013498:Suramin; D010734:Phosphogluconate Dehydrogenase; D008549:Melarsoprol