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Clinical Chemistry and Laboratory Medicine (CCLM)

Published in Association with the European Federation of Clinical Chemistry and Laboratory Medicine (EFLM)

Editor-in-Chief: Plebani, Mario

Ed. by Gillery, Philippe / Lackner, Karl J. / Lippi, Giuseppe / Melichar, Bohuslav / Schlattmann, Peter / Tate, Jillian R. / Tsongalis, Gregory J.

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Molecular targeting by homocysteine: a mechanism for vascular pathogenesis

Donald W. Jacobsen1 / Otilia Catanescu2 / Patricia M. DiBello3 / John C. Barbato4





Corresponding author: Donald W. Jacobsen, PhD, Department of Cell Biology, NC-10, Lerner Research Institute, Cleveland Clinic Foundation, 9500 Euclid Ave, Cleveland, OH 44195, USA Phone: +1-216-444-8340, Fax: +1-216-445-5480,

Citation Information: Clinical Chemical Laboratory Medicine. Volume 43, Issue 10, Pages 1076–1083, ISSN (Online) 1437-4331, ISSN (Print) 1434-6621, DOI: 10.1515/CCLM.2005.188, October 2005


Hyperhomocysteinemia is an independent risk factor for cardiovascular disease. Although there is a growing body of evidence that homocysteine plays a causal role in atherogenesis, specific mechanisms to explain the underlying pathology have remained elusive. This review focuses on chemistry unique to the homocysteine molecule to explain its inherent cytotoxicity. Thus, the high pKa of the sulfhydryl group (pKa=10.0) of homocysteine underlies its ability to form stable disulfide bonds with protein cysteine residues, and in the process, alters or impairs the function of the protein. Albumin, fibronectin, transthyretin, annexin II, and factor V have now been identified as molecular targets for homocysteine, and in the case of albumin, the mechanism of targeting has been elucidated.

Keywords: albumin; atherogenesis; disulfide bond; glutathione peroxidase; homocysteine; hyperhomocysteinemia; molecular targeting; pKa; sulfhydryl group; vascular pathogenesis

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