New insights into ethionamide metabolism: influence of oxidized methionine on its degradation path

乙硫异烟胺代谢的新见解:氧化蛋氨酸对其降解途径的影响

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作者:Nuno Vale, Diana Duarte, Alexandra Correia, Cláudia Alves, Patrícia Figueiredo, Hélder A Santos

Abstract

Ethionamide (ETH) is a commercial drug, used as a second-line resource to neutralize Mycobacterium tuberculosis infections. It is proven that its metabolization in the organism leads to the formation of the active form of the drug, but some metabolic pathways may lead to the loss of its activity. Our work proved that the presence of oxidized methionine in cells could influence ETH's degradation, leading to the appearance of an inactive metabolite that is detectable by HPLC and mass spectrometry. In addition, it was found this process increases with the degree of methionine oxidation. This study contributes to a better understanding of ethionamide's metabolism in living organisms, and can help in the design of new drugs or ethionamide boosters for the combat of multidrug resistant tuberculosis.

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