Role of molybdenum hydroxylases in diseases

ABSTRACT

The role of molybdenum-containing enzymes, aldehyde oxidase and xanthine oxidase in the production of reactive oxygen species has been discussed in term of mechanism of action. Unlike cytochrome P450 and other monooxygenase systems, the molybdenum hydroxylases carry out their reactions using water rather than molecular oxygen as the source of the oxygen atom incorporated into the product, and generated rather than consumed electrons. Aldehyde oxidase and xanthine oxidase differ in their substrates and inhibitor specificity. While aldehyde oxidase is a predominant oxidase, xanthine oxidase can undergo inter-conversion between oxidase/ dehydrogenase forms under pathological conditions such as ischaemia. Nevertheless, the wide range of drugs, xenobiotics and endogenous chemicals that interact with these enzymes, particularly aldehyde oxidase, highlight the importance of these enzymes in drug oxidation, detoxification and activation. Aldehyde oxidase and xanthine oxidase have been linked to some diseases such as neurodegenerative and ischaemic disorders, respectively. In vivo, oxidation of aldehyde oxidase-substrates such as ethanol-derived acetaldehyde, retinal and NADH may alter the balance of ROS production by this enzyme leading to neurological disorders, such as amyotrophic lateral sclerosis, Parkinson's disease and schizophrenia. In addition, aldehyde oxidase has been implicated in pathophysiology of alcohol liver injury, visual processes, synthesis of retinoic acid and reperfusion tissue injury. Under pathological conditions, such as ischaemia-reperfusion injury, both enzymes may participate