Properties of α-hydroxyacid dehydrogenase isozymes from Trypanosoma cruzi

Trypanosoma cruzi: inhibition of alpha-hydroxyacid dehydrogenase isozyme II by N-allyl and N-propyl oxamates and their effects on intact epimastigotes

“…In this investigation we designed, synthesized, and tested NPOx and NAOx, as well as the ethyl ester of these oxamates on the activity of T. cruzi HADH-isozyme II, because this isozyme has been associated with metabolic pathways supplying energy for the motility and survival of this parasite (Coronel et al 1981, Montamat et al 1987.…”

“…Isozyme I is responsible for the weak lactate dehydrogenase activity found in T. cruzi extracts (Coronel et al 1980). On the contrary isozyme II does not show activity against pyruvate and it is active on a broad of linear and branched chain substrates specially α-ketocaproate and α-ketoisocaproate (Coronel et al 1981). It is interesting that HADH-isozyme II found in T. cruzi, shows a substrate spectrum similar to that of LDH-C4 (Coronel et al 1981, Montamat et al 1988, suggesting that this HADH- isozyme II may also accomplish very specific functions in T. cruzi (Montamat et al 1987).…”

“…Enzyme preparations -HADH-isozyme I and II were purified as described by Coronel et al (1981), malate dehydrogenase (EC 1.1.1.37) L-malate:NAD oxidoreductase, glutamate dehydrogenase (EC 1.4.1.4) L-glutamate: NADP oxidoreductase (deaminating), malic enzyme (EC 1.1.1.40) L-malate:NADP oxidoreductase (oxaloacetate-decarboxylating), glucose-6-phosphate dehydrogenase (1.1.1.49) Dglucose-6-phosphate:NADP 1-oxidoreductase and succinate dehydrogenase (EC 1.3.99.1) succinate:(acceptor) oxidoreductase, were assayed in the crude extracts of T. cruzi.…”

“…On the contrary isozyme II does not show activity against pyruvate and it is active on a broad of linear and branched chain substrates specially α-ketocaproate and α-ketoisocaproate (Coronel et al 1981). It is interesting that HADH-isozyme II found in T. cruzi, shows a substrate spectrum similar to that of LDH-C4 (Coronel et al 1981, Montamat et al 1988, suggesting that this HADH- isozyme II may also accomplish very specific functions in T. cruzi (Montamat et al 1987). On account of the similarities between HADH-isozyme II and LDH-C4, it has been proposed that these isozymes are functionally homologous (Coronel et al 1981, Montamat et al 1987, 1988 and they must be integrated in metabolic pathways supplying energy for the motility of flagellum and survival of the parasite (Coronel et al 1981, Montamat et al 1987 or the spermatozoa, respectively (Coronel et al 1986).…”

“…Since HADH-isozyme II showed maximum activity with the substrates α-ketocaproate and α-ketoisocaproate (Coronel et al 1981), we assumed that N-allyl (NAOx) and N-propyl (NPOx) oxamates would fulfill the structural and steric requirements to be competitive and selective inhibitors of T. cruzi HADH-isozyme II, due to the close chemical structure existing between NAOx and NPOx and the substrates α-ketocaproate and α-ketoisocaproate. Thus, we decided to synthesize NAOx and NPOx and to investigate the effect of these substances on the activity of HADH-isozyme II from T. cruzi.…”