Dynamic state of glutathione in blood plasma

Recent studies have shown that there is an interorgan cycle of glutathione metabolism in which glutathione is translocated from certain cells into the blood plasma, and that plasma glutathione is utilized by cells that have gamma-glutamyl transpeptidase. The present studies indicate that there is a significant intravascular phase of glutathione metabolism. The level of total glutathione (GSH + GSSG) in rat blood plasma was found to be 22 to 27 microM GSH equivalents, as determined by the glutathione reductase recycling method. About 85% of the total is in the form of GSH. These findings contrast with previous reports of total levels of 3 to 6 microM and 50 to 75% GSSG. We found that plasma allowed to stand at 23 degrees C for 30 to 60 min has total glutathione levels of 4 to 7 microM, most (95%) of which is GSSG; after treatment of this plasma (following deproteinization) with KBH4, levels of 21 to 24 microM were found. GSH disappears rapidly from plasma, whereas GSSG disappears very slowly. gamma-Glutamyl transpeptidase does not account for the loss of plasma GSH, nor does binding to proteins account for more than a small fraction of the GSH that disappears. Most of the GSH that disappears can be found in the deproteinized samples after treatment with KBH4. The findings are in accord with the view that glutathione is translocated to plasma in the form of GSH and that such GSH constitutes the major source of plasma thiol. The intravascular phase of GSH metabolism seems to involve reduction of disulfide bonds of plasma constituents and mobilization of compounds bound by disulfide linkage to plasma proteins to form GSSG and low molecular weight derivatives of glutathione such as disulfides.