Rapid autoxidation of ferrous heme-A complexes relevant to Alzheimer's disease
CHEMICAL COMMUNICATIONS(2024)
摘要
Heme bound A beta peptides have been reported to reduce O2 by 2e- to H2O2 which may result in oxidative stress commonly encountered in Alzheimer's disease. In this study we report the first instance of rapid freeze quench trapping and characterizing the heme(iii)-O2- intermediate involved in the heme-A beta induced formation of partially reduced oxygen species (PROS) in physiologically relevant aqueous medium using absorption and resonance Raman spectroscopy. The kinetics of this process indicates a key role of the Tyr10 residue, unique to human A beta, in the generation of H2O2 from O2. The heme(iii)-O2- intermediate is a key detrimental species in the heme-A beta mediated oxidative stress generation in Alzheimer's disease via H2O2 formation in aqueous medium and Tyr10 residue plays an important role.
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