The bifunctional aldehyde–alcohol dehydrogenase controls ethanol and acetate production in Entamoeba histolytica under aerobic conditions

By applying metabolic control analysis and inhibitor titration we determined the degree of control (flux control coefficient) of pyruvate:ferredoxin oxidoreductase (PFOR) and bifunctional aldehyde–alcohol dehydrogenase (ADHE) over the fluxes of fermentative glycolysis of Entamoeba histolytica subjected to aerobic conditions. The flux-control coefficients towards ethanol and acetate formation determined for PFOR titrated with diphenyleneiodonium were 0.07 and 0.09, whereas for ADHE titrated with disulfiram were 0.33 and −0.19, respectively. ADHE inhibition induced significant accumulation of glycolytic intermediates and lower ATP content. These results indicate that ADHE exerts significant flux-control on the carbon end-product formation of amoebas subjected to aerobic conditions.

► Control of the glycolytic flux was analyzed in Entamoeba histolytica under aerobic conditions.
► ADHE and PFOR control on ethanol and acetate formation was determined by inhibitor titration.
► ADHE exerted higher flux control than PFOR over fermentative glycolysis under aerobic conditions.
► Disulfiram ADHE inhibition promoted accumulation of glycolytic intermediates and low ATP content.
► ADHE (and disulfiram) showed potential to become an alternative therapeutic target (and drug).