Homocysteine inhibits hydrogen peroxide breakdown by catalase

Abstract

Catalase, an antioxidant enzyme responsible for degradation of hydrogen peroxide, is protective in many diseases. The amino-acid homocysteine has been suggested to be a pro-oxidant with elevated levels linked to the oxidative stress seen in Alzheimer's and other diseases. This study shows that homocysteine inhibits the breakdown of hydrogen peroxide by catalase. Physiological concentrations of homocysteine inhibited catalase breakdown of hydrogen peroxide. The inhibition of catalase was by generation of the inactive catalase compound II and prevented by ethanol or NADPH but unaffected by iron. Physiological concentrations of homocysteine also inhibited cellular catalase but were not cytotoxic. homocysteine enhanced the toxicity of the amyloid-β peptide in an in vitro model of Alzheimer's neurodegeneration. The antioxidant vitamin E blocked the toxicity of amyloid-β plus homocysteine but not the catalase inhibition. Catalase inhibition by homocysteine may increase the levels of hydrogen peroxide and play a role in the pathology of disease.