Homocysteine promotes the LDL oxidase activity of ceruloplasmin

Ceruloplasmin (CP) oxidises low density lipoprotein (LDL). The oxidising potential depends on the formation of Cu2+-CP which is redox-cycled during oxidation. Homocysteine (HCY) reduces free Cu2+, potentiating its cell-damaging property. We show that HCY enhanced LDL oxidation by CP, but did not activate the LDL oxidising potential of Cu2+-diamine oxidase. Selective removal of the redox-active Cu2+ abolished the LDL oxidase activity of CP. However, HCY partially restored the LDL oxidase activity of redox-copper depleted CP, indicating that the remaining six copper atoms in CP may also be involved in the process. Spectroscopic and oxidation inhibition studies using the Cu+-reagent bathocuproine revealed that HCY induced Cu+-CP formation, thus promoting its LDL oxidase activity. (C) 2002 Federation of European Biochemical Societies. Published by Elsevier Science B.V. All rights reserved.