Inhibition of glyceraldehyde-3-phosphate dehydrogenase by pentalenolactone in Trypanosoma brucei.

Pentalenolactone (PL), an antibiotic produced by several strains of Streptomycetes, is a specific irreversible inhibitor of glyceraldehyde-3-phosphate dehydrogenase (EC 1.2.1.12). The effect of this antibiotic was studied in Trypanosoma brucei. In infected mice, due to the rapid metabolic inactivation of PL in vivo, trypanosomes were not affected by concentrations that were lethal to the host. Bloodstream trypanosomes in vitro were killed by low concentrations of PL (1.5 microgram ml-1), suggesting that there is no alternative to the glycolytic pathway for the generation of ATP in the bloodstream forms. In contrast, even high concentrations of PL (75 micrograms ml-1) were unable to inhibit growth of the procyclic form in vitro, presumably due to their ability to generate ATP independently of the glycolytic pathway.