NEW ENZYMATIC PATHWAYS FOR THE REDUCTION OF REACTIVE OXYGEN SPECIES IN Entamoeba histolytica

CABEZA, MATÍAS S.; GUERRERO, SERGIO A.; IGLESIAS, ALBERTO A.; ARIAS, DIEGO G.

BIOCHIMICA ET BIOPHYSICA ACTA-GENERAL SUBJECTS

ELSEVIER SCIENCE BV

Lugar: Amsterdam; Año: 2015 vol. 1850 p. 1233 - 1244

0304-4165

BackgroundEntamoeba histolytica, an intestinal parasite that is the causative agent of amoebiasis, isexposed to elevated amounts of highly toxic reactive oxygen and nitrogen speciesduring tissue invasion. A flavodiiron protein and a rubrerythrin have been characterizedin this human pathogen, although their physiological reductants have not beenidentified.MethodsThe present work deals with biochemical studies performed to reach a betterunderstanding of the kinetic and structural properties of rubredoxin reductase and twoferredoxins from E. histolytica.ResultsWe complemented the characterization of two different metabolic pathways for O2 andH2O2 detoxification in E. histolytica. We characterized a novel amoebic protein withrubredoxin reductase activity that is able to catalyze the NAD(P)H-dependent reductionof heterologous rubredoxins, amoebic rubrerythrin and flavodiiron protein but notferredoxins. In addition, the protein exhibited NAD(P)H oxidase activity, whichgenerates hydrogen peroxide from molecular oxygen. We describe how differentferredoxins were also efficient reducing substrates for both flavodiiron protein andrubrerythrin.Conclusions and General SignificanceThe enzymatic systems herein characterized could contribute to the in vivodetoxification of O2 and H2O2, playing a key role for the parasite defense againstreactive oxidant species. To the best of our knowledge this is the first characterizationof a eukaryotic rubredoxin reductase, including a novel kinetic study on ferredoxindependentreduction of flavodiiron and rubrerythrin proteins.342