Abstract
Imidazole dipeptides (IDPs), such as carnosine, are abundant in meat and have exhibited antioxidant and anti-fatigue properties, contributing to the health benefits associated with meat consumption. However, the detailed mechanisms underlying their physiological activities remain unclear. Recently, we identified the endogenous production of 2-oxo-IDPs, novel oxidized derivatives of IDPs, using mass spectrometry, and demonstrated that their production is associated with oxidative stress. Moreover, we investigated the chemical properties of 2-oxo-IDPs and revealed that they exhibit potent antioxidant capacity, radical-scavenging activity, and cytoprotective effects. Notably, 2-oxo-IDPs resist degradation by carnosinase 1, the carnosine-specific degrading enzyme, and are more stable than carnosine in human serum and Syrian hamsters. Furthermore, we established a highly sensitive method for the absolute quantification of IDPs and 2-oxo-IDPs using mass spectrometry and revealed that 2-oxo-IDPs are contained in various meat samples as well as IDPs. These findings indicate that 2-oxo-IDPs are bioactive molecules present in meat and strongly suggest that they are the primary contributors to the antioxidant effects of IDPs. The finding that IDPs are converted into 2-oxo-IDPs, thereby acquiring antioxidant activity and resistance to degradative enzymes, provides new insights into the roles and potential applications of IDPs and 2-oxo-IDPs in food science and redox biology. In addition, these findings highlight the significant potential of 2-oxo-IDPs as a foundation for the future development of preventive and therapeutic strategies, as well as for advancing drug discovery research.
