Biotransformation of xenobiotics by amine oxidases

Abstract

Although the cytochrome P450 (CYP) system ranks first in terms of catalytic versatility and the wide range of xenobiotics it detoxifies or activates to reactive intermediates, the contribution of amine oxidases and in particular of monoamine oxidases (MAOs) to the metabolism of xenobiotics is far from negligible but has been largely neglected. In this review on the involvement of amine oxidases in the metabolism of xenobiotics, the major characteristics reported for the CYP system (protein, reaction, tissue distribution, subcellular localisation, substrates, inhibitors, inducers, genetic polymorphism, impact of different physiopathological conditions on the activity, turnover) will be compared, whenever possible, with the corresponding characteristics of amine oxidases (MAOs in particular). The knowledge of the involvement of MAO-A, -B or both in the metabolism of a drug allows us to predict interactions with selective or non-selective MAO inhibitors (e.g. the metabolism of a drug deaminated by both forms of MAO is not necessarily inhibited in vivo by a selective MAO-A or -B inhibitor). If a drug is metabolized by MAOs, competitive interactions can occur with other drugs that are MAO substrates, e.g. with beta-adrenoceptor agonists and antagonists, prodrugs of dopamine, serotonin 5-HT1-receptor agonists as well as with primaquine, flurazepam and citalopram. Moreover, the knowledge of the involvement of MAOs in the metabolism of a drug may suggest possible, although not obligatory, interactions with tyramine-containing food or drink, with over the counter medicines sold to relieve the symptoms of coughs and colds (generally containing the indirectly-acting sympathomimetic amine phenylpropanolamine) or with phenylephrine-containing preparations. Finally, biotransformation by amine oxidases, as by CYP, does not always lead to detoxication but can produce toxic compounds.

Characterization of Human Urinary Metabolites of the Antimalarial Piperaquine

“…The resulting hydroxypiperaquine would undergo spontaneous cleavage into an aldehyde and an amine molecule, which could be further oxidized to the carboxylic acid. Although P450 is the most common metabolizing enzyme system of xenobiotics, the contribution of MAO is significant in the oxidative N-dealkylation of primary, secondary, and tertiary amines (Benedetti, 2001). A similar metabolic pattern, as proposed for PQ, can be seen for citalopram where an aldehyde is formed from the tertiary amine by MAO and further oxidized to the corresponding carboxylic acid by aldehyde oxidase (Rochat et al, 1998).…”

Brain region-specific perfluoroalkylated sulfonate (PFSA) and carboxylic acid (PFCA) accumulation and neurochemical biomarker Responses in east Greenland polar Bears (Ursus maritimus)

“…MAO is responsible for the metabolism of dopamine and other aminecontaining neurotransmitters (Rutledge and Jonason, 1967). MAO is also involved in the metabolism of xenobiotics (pollutants and pharmaceuticals) (Benedetti, 2001). The present study showed a positive relationship between MAO activity and PFAS across brain regions in all of the tested correlations, which may indicate xenobiotic induced stress and concurrent elevated activity of protective enzymes.…”

Bioactive Amines: Aspects of Quality and Safety in Food

“…The bioactive amines present in food represent a health hazard when consumed in large amount if the natural mechanism for their catabolism is impaired by disease or pharmacological agents or if the individual is genetically deficient [23,30]. Under normal conditions, amines ingested through foods are quickly metabolized by conjugation or by oxidation reactions by amine oxidase enzymes such as monoamine oxidase (MAO), diamine oxidase (DAO), polyamine oxidases (PAO) and N-methyl transferase [21,[31][32][33]. Individuals with respiratory and coronary heart diseases, hypertension problems or vitamin B12 deficiency are at risk because they are sensitive to smaller amounts of amines [4,5,34].…”