REDOX STATUS AND PROTEIN-BINDING OF PLASMA AMINOTHIOLS DURING THE TRANSIENT HYPERHOMOCYSTEINEMIA THAT FOLLOWS HOMOCYSTEINE ADMINISTRATION

We administered reduced L-homocysteine perorally (67 mumol/kg of body wt) to 12 healthy subjects and injected the same dose into one person, and determined the kinetics of the alterations in reduced, oxidized, and protein-bound concentrations of homocysteine, cysteine, and cystei nylglycine. After oral intake, reduced homocysteine increased rapidly (t(max) less-than-or-equal-to 15 min), reaching concentrations [3.97 ( SD 2.99) mumol/L] 20-fold above fasting values, and then declined towa rds the normal concentration within 2 h. There was a similar increase in reduced cysteine and a moderate increase in reduced cysteinylglycin e. During this response, we observed a positive correlation between th e reduced/total ratio for homocysteine and cysteine. When homocysteine was injected, the increase in reduced homocysteine preceded the incre ase in reduced cysteine by about 3 min. After oral loading, oxidized h omocysteine showed a transient increase (t(max) = 30 min) that lagged behind the increase of reduced homocysteine. Oxidized cysteine and cys teinylglycine were stable or decreased slightly. Protein-bound homocys teine increased the least rapidly after homocysteine administration (t (max) = 1-2 h), and returned to normal values slowly. Changes in prote in-bound homocysteine essentially mirrored a concurrent decrease in pr otein-bound cysteine, suggesting displacement of bound cysteine. These data show that plasma homocysteine has a pronounced, direct effect on the redox status and protein binding of other plasma thiol components . Such effects should be recognized when studying the mechanisms behin d the atherogenic effect of increased plasma homocysteine.