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.

中文翻译：

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乙硫异烟胺代谢的新见解：氧化蛋氨酸对其降解路径的影响

乙硫异烟胺 (ETH) 是一种商业药物，用作中和结核分枝杆菌感染的二线资源。已证明其在生物体内的代谢导致药物活性形式的形成，但某些代谢途径可能导致其活性丧失。我们的工作证明，细胞中氧化蛋氨酸的存在会影响 ETH 的降解，导致出现可通过 HPLC 和质谱法检测到的无活性代谢物。此外，发现该过程随着甲硫氨酸氧化程度的增加而增加。这项研究有助于更好地了解乙硫异烟胺在生物体中的代谢，并有助于设计新药或乙硫异烟胺增强剂以对抗耐多药结核病。