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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 / Greaves, Ronda / Lackner, Karl J. / Lippi, Giuseppe / Melichar, Bohuslav / Payne, Deborah A. / Schlattmann, Peter


IMPACT FACTOR 2018: 3.638

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Volume 43, Issue 10

Issues

Molecular targeting by homocysteine: a mechanism for vascular pathogenesis

Donald W. Jacobsen
  • Department of Cell Biology, Lerner Research Institute, Cleveland Clinic Foundation, Cleveland, OH, USA and Department of Molecular Medicine, Cleveland Clinic Lerner College of Medicine, Case Western Reserve University, Cleveland, OH, United States of America
  • Other articles by this author:
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/ Otilia Catanescu
  • Department of Cell Biology, Lerner Research Institute, Cleveland Clinic Foundation, Cleveland, OH, United States of America
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/ Patricia M. DiBello
  • Department of Cell Biology, Lerner Research Institute, Cleveland Clinic Foundation, Cleveland, OH, United States of America
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/ John C. Barbato
  • Department of Cell Biology, Lerner Research Institute, Cleveland Clinic Foundation, Cleveland, OH, United States of America
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Published Online: 2011-09-21 | DOI: https://doi.org/10.1515/CCLM.2005.188

Abstract

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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About the article

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,


Published Online: 2011-09-21

Published in Print: 2005-10-01


Citation Information: Clinical Chemistry and Laboratory Medicine (CCLM), Volume 43, Issue 10, Pages 1076–1083, ISSN (Online) 1437-4331, ISSN (Print) 1434-6621, DOI: https://doi.org/10.1515/CCLM.2005.188.

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Molecular Nutrition & Food Research, 2008, Volume 52, Number 11, Page 1324
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American Journal of Nephrology, 2007, Volume 28, Number 2, Page 254
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Amino Acids, 2007, Volume 32, Number 4, Page 561
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Kidney International, 2006, Volume 69, Number 5, Page 787

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