Relationships among Plasma Homocysteine, Cysteine, and Albumin Concentrations: Potential Utility of Assessing the Cysteine/Homocysteine Ratio

摘要

McCully (1) initially observed that patients with extremely increased plasma concentrations of homocysteine (Hcy) attributable to homocystinuria have accelerated atherosclerosis. Subsequently, even moderate hyperhomocysteinemia became recognized as a risk factor for atherosclerosis and thrombosis (2)(3)(4), although the mechanism by which increased concentrations of Hcy produce these effects is uncertain. Hcy occurs in the circulation in multiple forms, including Hcy linked via disulfides to albumin (～70%), as a mixed disulfide with Cys (25%), as a disulfide-linked dimer (5%), as the free reduced amino acid (5%), and as a thiolactone (trace) (5)(6). It is not clear which of these components are physiologically active, and efforts to measure individual components have been technically challenging because of the interconversion of different forms during specimen processing. As a result, measurement of total Hcy (tHcy), including all forms except the trace amount of thiolactone, has become the standard clinical test (5)(6)(7).The present study examined the relationships among concentrations of tHcy, plasma albumin, and total Cys (tCys; includes protein-bound, disulfide-linked forms, and reduced). Considering that albumin and Cys serve as covalent carriers of most of the Hcy in circulation, these components may affect circulating tHcy and the physiological action of Hcy. Cys has the potential for multiple interactions with Hcy because Cys is not only a covalent carrier but also a competitor for binding sites on proteins, a potential competitor …