Amino Acids

, Volume 32, Issue 4, pp 561–572 | Cite as

Mechanisms of homocysteine toxicity in humans

  • J. Perła-KajánEmail author
  • T. Twardowski
  • H. Jakubowski
Review Article


Homocysteine, a non-protein amino acid, is an important risk factor for ischemic heart disease and stroke in humans. This review provides an overview of homocysteine influence on endothelium function as well as on protein metabolism with a special respect to posttranslational modification of protein with homocysteine thiolactone. Homocysteine is a pro-thrombotic factor, vasodilation impairing agent, pro-inflammatory factor and endoplasmatic reticulum-stress inducer. Incorporation of Hcy into protein via disulfide or amide linkages (S-homocysteinylation or N-homocysteinylation) affects protein structure and function. Protein N-homocysteinylation causes cellular toxicity and elicits autoimmune response, which may contribute to atherogenesis.

Keywords: Homocysteine – Homocysteine thiolactone – Protein N-homocysteinylation – Toxicity – Autoantibodies – Protein S-homocysteinylation 



activated protein C


bleomycin hydrolase


endoplasmatic reticulum


high density lipoprotein


homocysteine thiolactone


low density lipoprotein


methionyl-tRNA synthetase


methionine synthase








tissue plasminogen activator


unfolded protein response


vascular endothelial growth factor


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Copyright information

© Springer-Verlag 2007

Authors and Affiliations

  • J. Perła-Kaján
    • 1
    Email author
  • T. Twardowski
    • 1
  • H. Jakubowski
    • 1
    • 2
  1. 1.Institute of Bioorganic ChemistryPolish Academy of SciencesPoznańPoland
  2. 2.UMDNJ-New Jersey Medical SchoolNewarkU.S.A.

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