Protective mechanisms against protein damage in hyperhomocysteinemia: Systemic and renal detoxification of homocysteine-thiolactone

Abstract

Homocysteine (Hcy) and its metabolite Hcy-thiolactone (HTL) are implicated in cardiovascular disease (CVD). Recent studies show that HTL is a predictor of acute myocardial infarction in CVD patients, independent of established risk factors and plasma total Hcy. HTL is formed in all cell types as a result of error-editing reactions in protein biosynthesis. Its ability to N-homocysteinylate protein lysine residues and cause protein damage has been mechanistically linked to the pathology of CVD induced by hyperhomocysteinemia. Specific HTL-detoxifying mechanisms have been identified that can potentially be exploited for modulation of HTL levels and the risk of CVD.