Dehydromethionine is a common product of methionine oxidation by singlet molecular oxygen and hypohalous acids

Methionine is one of the main targets for biological oxidants. Its reaction with the majority of oxidants generates only methionine sulfoxide. However, when N-terminal methionine reacts with hypohalous acids (HOCl and HOBr) or singlet molecular oxygen (¹O₂), it can also generate a cyclic product called dehydromethionine (DHM). Previously, DHM was suggested as a biomarker of oxidative stress induced by hypohalous acids. However, DHM can also be generated by ¹O₂ -oxidation of methionine, and the contribution of this pathway of DHM formation in a context of a site-specific redox imbalance in an organism is unknown. In this work, a through comparison of the reactions of hypohalous acids and ¹O₂ with methionine, either free or inserted in peptides and proteins was undertaken. In addition, we performed methionine photooxidation in heavy water (H₂¹⁸O) to determine the influence of the pH in the mechanism of DHM formation. We showed that for free methionine, or methionine-containing peptides, the yields of DHM formation in the reactions with ¹O₂ were close to those achieved by HOBr oxidation, but much higher than the yields obtained with HOCl as the oxidant. This was true for all pH tested (5, 7.4, and 9). Interestingly, for the protein ubiquitin, DHM yields after reaction with ¹O₂ were higher than those obtained with both hypohalous acids. Our results indicate that ¹O₂ may also be an important source of DHM in biological systems.