Possible Interaction: Copper and Homocysteine

“Different experimental studies have suggested that homocysteine Hcy ) exerts a pro-oxidant effect in the presence of metal ions (Fe and Cu).”

“Cu chelator penicillamine can significantly diminish the inhibitory effect of Hcy on endothelial function, which has led to the interpretation that Cu mediates the deleterious effect of Hcy.”

“High levels of Hcy do not affect the process of microtubule formation, but the combination of Cu and Hcy leads to a significant inhibitory effect.”

“Why does Cu produce adverse effects when it co-exists with Hcy?”

“Due to a possible link between hyperhomocysteinemia and AD, we examined whether interaction between homocysteine and Cu could potentiate Cu neurotoxicity.”

“ Homocysteine also generated high levels of hydrogen peroxide in the presence of Cu (II) and promoted Aβ/Cu‐mediated hydrogen peroxide production and neurotoxicity.”

“ Homocysteine was shown to selectively potentiate toxicity from low micromolar concentrations of Cu.”

“In contrast to the other metal ions, copper ions also increased the release of homocysteine into the medium, possibly through interaction with S-adenosylhomocysteine hydrolase.”

“In initial experiments with a cell-free system, micromolar amounts of copper were found to catalyze an oxygen-dependent oxidation of homocysteine.”

“Specific injury to endothelial cells was seen only after 4 h of incubation with homocysteine plus copper.”

“Using cultured human and bovine endothelial cells, we found that homocysteine plus copper could lyse the cells in a dose-dependent manner, an effect that was completely prevented by catalase.”

“Men supplemented with copper have decreased homocysteine in plasma2-4.”

“HPLC-ICP-MS analysis revealed that Hcy caused alterations in the distribution of intracellular Cu ; more Cu was redistributed to low molecular weight fractions.”

“ Hcy also decreased the protein levels of Cu chaperone COX17, which was accompanied by a decrease in the activity of cytochrome c oxidase (CCO) and a collapse of mitochondrial membrane potential.”

“ Hcy decreased intracellular Cu concentrations.”

“Pretreatment of the cells with a final concentration of 5 µM Cu in cultures prevented the effects of Hcy.”

“Previous studies suggested that Hcy interferes with copper (Cu) metabolism in vascular endothelial cells.”

“The study thus demonstrated that Hcy disturbs Cu homeostasis and limits the availability of Cu to critical molecules such as COX17 and CCO, leading to mitochondrial dysfunction and endothelial cell injury.”

“These effects of Hcy were all preventable by Cu pretreatment.”

“In addition to finding that Hcy is involved in cholesterol homeostasis in neurons, we demonstrate that the combined effect of cholesterol and Hcy in the presence of copper significantly increases the levels of reactive oxygen species and may render neurons more vulnerable to Aβ.”

“Hepatotoxic and neurotoxic effects of homocysteine (Hcy), as well as interrelationships between Hcy and Cu toxicity, were documented.”

“Abstract Hyperhomocysteinemia is a risk factor for neurodegeneration, and binding of copper by homocysteine is a putative underlying mechanism.”