title: Mechanisms for the formation of protein-bound homocysteine in human plasma.
abstract: Hyperhomocysteinemia is an independent risk factor for cardiovascular disease. Greater than 70% of homocysteine in circulation is protein-bound. An in vitro model system using human plasma has been developed to study mechanisms of protein-bound homocysteine formation and establish the equilibrium binding capacities of plasma for homocysteine. Addition of homocysteine to plasma caused an initial rapid displacement of cysteine and a subsequent increase in protein-bound homocysteine. This rapid reaction was followed by a slower oxygen-dependent reaction forming additional protein-bound homocysteine. To determine the equilibrium binding capacity of plasma proteins for homocysteine, plasma was treated with 0.5-10 mM dl-homocysteine for 4 h at 37 degrees C under aerobic conditions. Under these conditions the equilibrium binding capacity was 4.88 +/- 0.51 and 4.74 +/- 0.68 micromol/g protein for male (n = 10) and female (n = 10) donors, respectively. The mechanism of protein-bound homocysteine formation involves both thiol-disulfide exchange and thiol oxidation reactions. We conclude that plasma proteins have a high capacity for binding homocysteine in vitro.
authors.affiliation: Department of Cell Biology, Cleveland Clinic Foundation, Cleveland, Ohio, USA.
authors.forename: T
authors.initials: T
authors.lastname: Togawa
authors.forename: S
authors.initials: S
authors.lastname: Sengupta
authors.forename: H
authors.initials: H
authors.lastname: Chen
authors.forename: K
authors.initials: K
authors.lastname: Robinson
authors.forename: I
authors.initials: I
authors.lastname: Nonevski
authors.forename: A K
authors.initials: AK
authors.lastname: Majors
authors.forename: D W
authors.initials: DW
authors.lastname: Jacobsen
mesh_terms: D001798:Blood Proteins / Q000378:metabolism*; D005260:Female; D006710:Homocysteine / Q000097:blood* / Q000378:metabolism; D006801:Humans; D066298:In Vitro Techniques; D008297:Male; D010101:Oxygen Consumption; D011485:Protein Binding; D013997:Time Factors
chemical_list: D001798:Blood Proteins; D006710:Homocysteine