Ascorbate peroxidase (APX)

Ascorbate peroxidase (APX) is a heme-containing peroxidase primarily identified in plants, algae, and some protozoa, where it plays a pivotal role in the detoxification of hydrogen peroxide (H2O2) using ascorbate as an electron donor. It is an integral component of the ascorbate-glutathione cycle, maintaining cellular redox homeostasis and protecting against oxidative damage to lipids, proteins, and nucleic acids. APX is a significant therapeutic target because it is essential for the survival of kinetoplastid parasites, such as Leishmania and Trypanosoma cruzi, while being entirely absent in humans. Inhibition of APX leads to lethal oxidative stress within the pathogen, effectively triggering apoptosis-like death. Clinical research has also linked the overexpression of APX to drug resistance against established treatments like Amphotericin B and benznidazole, highlighting its potential as a target for overcoming drug resistance. Although specific APX-targeting drugs are not yet clinically approved, experimental inhibitors like salicylhydroxamic acid and structural analogs are being explored to disrupt the antioxidant defenses of infectious agents selectively.

Other names

L-ascorbate:hydrogen-peroxide oxidoreductaseAscorbate-dependent peroxidaseL-ascorbic acid peroxidaseAscorbic acid peroxidaseAP

Inhibition of the enzyme's catalytic activity prevents the reduction of hydrogen peroxide to water, leading to the accumulation of reactive oxygen species and subsequent oxidative damage and apoptosis in the pathogen.