Mechanisms for the formation of protein-bound homocysteine in human plasma.
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.
Togawa
T
T
Department of Cell Biology, Cleveland Clinic Foundation, Cleveland, Ohio, USA.
Sengupta
S
S
Chen
H
H
Robinson
K
K
Nonevski
I
I
Majors
A K
AK
Jacobsen
D W
DW
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
D001798:Blood Proteins; D006710:Homocysteine