Aldehyde oxidase 1 (AOX1)

Aldehyde oxidase 1 (AOX1) is a cytosolic enzyme belonging to the xanthine oxidase family of molybdo-flavoenzymes. It forms homodimers and requires cofactors such as FAD, molybdenum (MoCo), and iron–sulfur clusters for activity. AOX1 catalyzes the oxidation of a broad range of endogenous and exogenous aldehydes—as well as aza-heterocyclic aromatic compounds—into carboxylic acids or hydroxylated products. This enzyme is one of the major phase I drug-metabolizing enzymes in human liver, contributing significantly to the clearance of various drugs and xenobiotics, and exhibits broad substrate specificity. Its interindividual enzymatic activity is highly variable due to genetic polymorphisms, leading to significant implications for drug pharmacokinetics, efficacy, and safety. AOX1 is also a notable target for drug interactions, with several clinically used drugs acting as its substrates or inhibitors, and is under consideration in drug development for predicting and mitigating adverse reactions and therapeutic failure.

Other names

Aldehyde oxidaseAOX1AOAOH1Azaheterocycle hydroxylase

Oxidative metabolism (oxidation of aldehydes and N-heterocycles in drugs and xenobiotics). Drug inhibition of AOX1 prevents metabolism of substrate drugs, increasing their bioavailability or leading to drug-drug interactions.