Sulfheme formation during homocysteine S-oxygenation by catalase in cancers and neurodegenerative diseases.

ABSTRACT: Accumulating evidence suggests that abnormal levels of homocysteine are associated with vascular dysfunctions, cancer cell proliferation and various neurodegenerative diseases. With respect to the latter, a perturbation of transition metal homeostasis and an inhibition of catalase bioactivity have been reported. Herein, we report on some of the molecular bases for the cellular toxicity of homocysteine and demonstrate that it induces the formation of sulfcatalase, an irreversible inactive state of the enzyme, without the intervention of hydrogen sulfide. Initially, homocysteine reacts with native catalase and/or redox-active transition metal ions to generate thiyl radicals that mediate compound II formation, a temporarily inactive state of the enzyme. Then, the ferryl centre of compound II

SUBMITTER: Padovani D 

PROVIDER: S-EPMC5116089 | biostudies-literature | 2016 Nov

REPOSITORIES: biostudies-literature