Rapid autoxidation of ferrous heme-Aβ complexes relevant to Alzheimer's disease

Abstract

Heme bound Aβ 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-Aβ 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 Aβ, in the generation of H₂O₂ from O₂.