Plasma methionine and cysteine kinetics in response to an intravenous glutathione infusion in adult humans

Glutathione (GSH), a tripeptide (gamma-glutamyl-cysteinyl-glycine), is thought to be both a storage and a transport form of cysteine (Cys). In a previous study (T. Hiramatsu, N. K. Fukagawa, J. S. Marchini, J. Cortiella, Y.-M. Yu, T. E. Chapman, and V. R. Young. Am. J. Clin. Nutr. 60: 525-533, 1994), the direct tracer-derived estimate of Cys flux was considerably higher than that predicted from estimates of protein turnover. To further examine the components of plasma Cys flux, seven normal-weight healthy adult men and women (26 +/- 2 yr) received stable isotope tracer infusions of L-[methyl-H-2(3);1-C-13] methionine, L-[3,3-H-2(2)] cysteine, and L- [methyl-H-2(3)]leucine for 460 min. After a 3-h baseline period, GSH was administered at similar to 32 mu mol . kg(-1). h(-1) until the end of the study. Expired breath and blood samples were obtained at timed intervals and analyzed for isotope enrichment using mass spectrometry. Leucine, alpha-ketoisocaproate, and methionine (carboxyl carbon, methyl moiety, remethylation, and transsulfuration) turnover were reduced during GSH administration (P < 0.01). In the final hour of GSH administration, Cys flux increased by 61% from 55.1 +/- 1.7 to 88.7 +/- 5.2 mu mol . kg(-1). h(-1) (P < 0.01), which was essentially equivalent to the rate of exogenous GSH infusion. These data suggest that GSH breakdown accounts for similar to 50% of tracer-derived Cys flux basally and for all of the increase in measured Cys turnover during exogenous GSH infusion.