Abstract by Steven York
Chemistry and Biochemistry
Homocysteinylation of Transferrin Reduces Iron Binding Efficiency
Elevated homocysteine (Hcy) correlates with inflammation and oxidative stress in patients with Alzheimer’s Disease (AD), Ocular degeneration, and Osteoarthritis. Free iron is known to cause oxidative stress, so under healthy condition iron is chaperoned by the serum iron binding protein transferrin (Tf) to prevent free radical generation. It has also been shown that Hcy can bind to proteins and alter their function. We propose that excess Hcy binds to Tf and inhibits its ability to efficiently bind iron. This would result in free serum iron and an increase in oxidative stress. We tested this hypothesis using biochemical iron loading assays and, mass spectrometry (MS) to assess if Hcy alters Tfs ability to bind iron. Tf incubated with Hcy for 72hrs. showed reduced iron binding affinity and MS analysis of these samples revealed Hcy bonded to Cys residues in TF.