Redox status and protein binding of plasma aminothiols during the transient hyperhomocysteinemia that follows homocysteine administration
Mansoor, M.A.; Guttormsen, A.B.; Fiskerstrand, T.; Refsum, H.; Ueland, P.M.; Svardal, A.M.
Clinical Chemistry 39(6): 980-985
1993
ISSN/ISBN: 0009-9147 PMID: 8504567 Document Number: 409068
We administered reduced L-homocysteine perorally (67 mu-mol/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 cysteinylglycine. After oral intake, reduced homocysteine increased rapidly (t-max ltoreq 15 min), reaching concentrations (3.97 (SD 2.99) mu-mol/L) 20-fold above fasting values, and then declined towards the normal concentration within 2 h. There was a similar increase in reduced cysteine and a moderate increase in reduced cysteinylglycine. During this response, we observed a positive correlation between the reduced/total ratio for homocysteine and cysteine. When homocysteine was injected, the increase in reduced homocysteine preceded the increase in reduced cysteine by about 3 min. After oral loading, oxidized homocysteine showed a transient increase (t-max = 30 min) that lagged behind the increase of reduced homocysteine. Oxidized cysteine and cysteinylglycine were stable or decreased slightly. Protein-bound homocysteine increased the least rapidly after homocysteine administration (t-max = 1-2 h), and returned to normal values slowly. Changes in protein-bound homocysteine essentially mirrored a concurrent decrease in proteinbound 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 behind the atherogenic effect of increased plasma homocysteine.