title: Trypanosoma cruzi expresses a plant-like ascorbate-dependent hemoperoxidase localized to the endoplasmic reticulum.
abstract: In most aerobic organisms hemoperoxidases play a major role in H(2)O(2)-detoxification, but trypanosomatids have been reported to lack this activity. Here we describe the properties of an ascorbate-dependent hemoperoxidase (TcAPX) from the American trypanosome Trypanosoma cruzi. The activity of this plant-like enzyme can be linked to the reduction of the parasite-specific thiol trypanothione by ascorbate in a process that involves nonenzymatic interaction. The role of heme in peroxidase activity was demonstrated by spectral and inhibition studies. Ascorbate could saturate TcAPX activity indicating that the enzyme obeys Michaelis-Menten kinetics. Parasites that overexpressed TcAPX activity were found to have increased resistance to exogenous H(2)O(2). To determine subcellular location an epitope-tagged form of TcAPX was expressed in T. cruzi, which was observed to colocalize with endoplasmic reticulum resident chaperone protein BiP. These findings identify an arm of the oxidative defense system of this medically important parasite. The absence of this redox pathway in the human host may be therapeutically exploitable.
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D060387:Ascorbate Peroxidases; D001205:Ascorbic Acid / Q000378:metabolism; D001483:Base Sequence; D016054:DNA, Protozoan / Q000235:genetics; D004721:Endoplasmic Reticulum / Q000201:enzymology; D017125:Genes, Protozoan; D006801:Humans; D006861:Hydrogen Peroxide / Q000378:metabolism / Q000494:pharmacology; D008969:Molecular Sequence Data; D010084:Oxidation-Reduction; D010544:Peroxidases / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D010944:Plants / Q000201:enzymology; D017386:Sequence Homology, Amino Acid; D014349:Trypanosoma cruzi / Q000187:drug effects / Q000201:enzymology* / Q000235:genetics
chemical_list: D016054:DNA, Protozoan; D006861:Hydrogen Peroxide; D010544:Peroxidases; D060387:Ascorbate Peroxidases; D001205:Ascorbic Acid