Amino Acids

, Volume 32, Issue 4, pp 561–572

Mechanisms of homocysteine toxicity in humans

Review Article

DOI: 10.1007/s00726-006-0432-9

Cite this article as:
Perła-Kaján, J., Twardowski, T. & Jakubowski, H. Amino Acids (2007) 32: 561. doi:10.1007/s00726-006-0432-9

Summary.

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

Abbreviations:

APC

activated protein C

BLH

bleomycin hydrolase

ER

endoplasmatic reticulum

HDL

high density lipoprotein

HTL

homocysteine thiolactone

LDL

low density lipoprotein

MetRS

methionyl-tRNA synthetase

MS

methionine synthase

PON

paraoxonase

SAH

S-adenosylhomocysteine

SAM

S-adenosylmethionine

TPA

tissue plasminogen activator

UPR

unfolded protein response

VEGF

vascular endothelial growth factor

Copyright information

© Springer-Verlag 2007

Authors and Affiliations

  • J. Perła-Kaján
    • 1
  • 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.