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J. Biol. Chem., Vol. 255, Issue 20, 9530-9533, 10, 1980
ME Anderson and A Meister
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.
Dynamic state of glutathione in blood plasma
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