Unraveling the Role of Metal Ions and Low Catalytic Activity of Cytochrome C Oxidase in Alzheimer’s Disease

Author： Alleyne Trevor Mohan Neetu Joseph Jerome Adogwa Andrew

ISSN： 0895-8696

Source： Journal of Molecular Neuroscience, Vol.43, Iss.3, 2011-03, pp. : 284-289

Disclaimer: Any content in publications that violate the sovereignty, the constitution or regulations of the PRC is not accepted or approved by CNPIEC.

Previous Menu Next

Abstract

Alzheimer’s disease (AD) is a neurodegenerative disorder characterized by high levels of aluminum and certain other metal ions in the brain: The disease is also characterized by low activity of brain cytochrome C oxidase (COX) but whether the elevated metal ions and the low COX activity are linked is not known. Moreover, COX is known to exhibit two catalytic rates (V _max) and two substrate binding constants (K _m) but it is not known which of these is affected in AD. In this study, we employed the Klatzo AD rabbit model to evaluate the impact of elevated metal ions on brain COX activity. New Zealand white rabbits were injected intra-cerebrally with 1.4% solutions of either AlCl₃, FeCl₃, CaCl₂, or MgCl₂; and 10 days, later the brain mitochondria were isolated. Polarographic assay revealed that compared to the controls, all four metals led to decreases in the V _max of the enzyme’s low affinity site. The respective decreases were; 16%, 36%, 18%, and 30%. The results suggest a sequence of events in vivo in which oxygen radical damage to mitochondria and COX leads to low ATP production and excess heme establishing conditions thought to be ideal for neurodegeneration.