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Consequences of homocysteine export and oxidation in the vascular system.
Semin Thromb Hemost. 2000; 26(3):227-32.ST

Abstract

The risk for arteriosclerosis and thrombosis of patients with severe hyperhomocysteinemia is reduced by homocysteine-lowering therapy. Whether this is the case in patients with mild hyperhomocysteinemia remains to be proved. Another challenge for researchers is to establish a satisfying pathological mechanism of the vasotoxicity of a disturbed homocysteine metabolism. Unfortunately, most in vitro studies use physiologically irrelevant concentrations or forms, or both, of homocysteine. The role of the different oxidized and reduced forms of homocysteine in its metabolism has gained little attention. In the cell, homocysteine is mainly present in its reduced form. In this article export of homocysteine out of the cell is reported to be regulated by a "reduced-homocysteine carrier." In vitro endothelial cells export homocysteine at a constant rate in a folate dose-dependent matter. Even at high-normal folate levels, endothelial cells export homocysteine. As soon as homocysteine is exported out of the cell, it will be oxidized to a disulfide with any compound containing a thiol function or undergo a disulfide exchange reaction, both resulting in formation of disulfides of homocysteine. Consequently, in plasma, about 99% of homocysteine is bound to disulfides. Before homocysteine can be metabolized, it needs to be taken up by the cell via carriers, channels, or receptors recognizing the different homocysteine disulfides. In the cell, the homocysteine disulfides are reduced, liberating homocysteine in its reduced form. Next, homocysteine can be metabolized after binding to the homocysteine-converting enzymes. In particular, the liver and kidney supposedly take up and metabolize significant amounts of homocysteine.

Authors+Show Affiliations

Department of Pediatrics, University Hospital Nijmegen, The Netherlands. h.blom@ckslkn.azn.nl

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't
Review

Language

eng

PubMed ID

11011840

Citation

Blom, H J.. "Consequences of Homocysteine Export and Oxidation in the Vascular System." Seminars in Thrombosis and Hemostasis, vol. 26, no. 3, 2000, pp. 227-32.
Blom HJ. Consequences of homocysteine export and oxidation in the vascular system. Semin Thromb Hemost. 2000;26(3):227-32.
Blom, H. J. (2000). Consequences of homocysteine export and oxidation in the vascular system. Seminars in Thrombosis and Hemostasis, 26(3), 227-32.
Blom HJ. Consequences of Homocysteine Export and Oxidation in the Vascular System. Semin Thromb Hemost. 2000;26(3):227-32. PubMed PMID: 11011840.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Consequences of homocysteine export and oxidation in the vascular system. A1 - Blom,H J, PY - 2000/9/30/pubmed PY - 2001/3/3/medline PY - 2000/9/30/entrez SP - 227 EP - 32 JF - Seminars in thrombosis and hemostasis JO - Semin Thromb Hemost VL - 26 IS - 3 N2 - The risk for arteriosclerosis and thrombosis of patients with severe hyperhomocysteinemia is reduced by homocysteine-lowering therapy. Whether this is the case in patients with mild hyperhomocysteinemia remains to be proved. Another challenge for researchers is to establish a satisfying pathological mechanism of the vasotoxicity of a disturbed homocysteine metabolism. Unfortunately, most in vitro studies use physiologically irrelevant concentrations or forms, or both, of homocysteine. The role of the different oxidized and reduced forms of homocysteine in its metabolism has gained little attention. In the cell, homocysteine is mainly present in its reduced form. In this article export of homocysteine out of the cell is reported to be regulated by a "reduced-homocysteine carrier." In vitro endothelial cells export homocysteine at a constant rate in a folate dose-dependent matter. Even at high-normal folate levels, endothelial cells export homocysteine. As soon as homocysteine is exported out of the cell, it will be oxidized to a disulfide with any compound containing a thiol function or undergo a disulfide exchange reaction, both resulting in formation of disulfides of homocysteine. Consequently, in plasma, about 99% of homocysteine is bound to disulfides. Before homocysteine can be metabolized, it needs to be taken up by the cell via carriers, channels, or receptors recognizing the different homocysteine disulfides. In the cell, the homocysteine disulfides are reduced, liberating homocysteine in its reduced form. Next, homocysteine can be metabolized after binding to the homocysteine-converting enzymes. In particular, the liver and kidney supposedly take up and metabolize significant amounts of homocysteine. SN - 0094-6176 UR - https://www.unboundmedicine.com/medline/citation/11011840/Consequences_of_homocysteine_export_and_oxidation_in_the_vascular_system_ L2 - http://www.thieme-connect.com/DOI/DOI?10.1055/s-2000-8467 DB - PRIME DP - Unbound Medicine ER -