Abstract by Steven York
Chemistry and Biochemistry
Homocysteinylation of Transferrin in Relation to Oxidative Stress and Neurodegeneration
Elevated homocysteine (Hcy) correlates with inflammation and oxidative stress in Alzheimer’s Disease (AD), Diabetes, and Kidney Disease. Free iron is the proposed cause of oxidative stress, but in healthy condition iron is chaperoned by the serum iron binding protein Transferrin (Tf). 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 resulting in free serum iron that increases 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. Preliminary MS analysis of Tf incubated with Hcy for 12hrs showed attachment of Hcy to Cys residues.