Mechanistic insights into the ROS‐mediated inactivation of human aldehyde oxidase

Abstract

Human aldehyde oxidase (hAOX1) is a molybdoenzyme that oxidizes aldehydes and N‐heterocyclic compounds, thereby generating hydrogen peroxide (H2O2) and superoxide during turnover. hAOX1 has been shown previously to be inactivated under turnover conditions by H2O2. Here, we investigated the effect of exogenously added H2O2 on the activity of hAOX1. We show that exogenously added H2O2 did not affect the enzyme activity under aerobic conditions, but completely inactivated the enzyme under anaerobic conditions. We propose that this effect is based on the reducing power of H2O2 and the susceptibility of the reduced molybdenum cofactor (Moco) to lose the sulfido ligand. When oxygen is present, the enzyme is rapidly reoxidized. We believe that our study is significant in understanding the detailed effect of reactive oxygen species on the inactivation of hAOX1 and other molybdoenzymes.