Uptake of glutathione by serum albumin of normal and tumor-bearing mice.

Single doses of 3SS-labeled reduced glutathione (GSH) were administered intraperitoneally to groups of normal and tumorbearing mice, and radioactivity was determined in the protein and non-protein fractions of blood serum. The results show that GSH is taken up rapidly by the albumin fraction of serum pro tein. Experiments in vitro showed that both mouse and human serum albumin react with GSH in aerobic mixtures at pH values near neutrality and yield a mixed disulfide through oxidation of their thiol groups. Unlike the intermediate mixed disulfides pro duced in the reduction of albumin disulfide groups by GSH at low pH under anaerobic conditions, this mixed disulfide is rela tively stable in slightly alkaline solution and exhibits no apparent change in the tertiary structure of the albumin moiety. It releases free GSH on incubation with tumor and liver homogenates. The findings indicate that albumin and GSH may interact by two different mechanisms which are operative depending on the pH and on the presence or absence of free oxygen in the medium. The possible physiologic significance of these mechanisms is dis cussed.