The most widely recognized function of reduced glutathione (GSH) is its def
ense against tonic compounds, whether exogenous, such as electophilic xenob
iotics, or endogenous, such as reactive oxygen species, generated during no
rmal oxidative metabolism and/or stress. However; another no less significa
nt role of GSH-namely its function as a reservoir and vehicle for packaging
and transport of cyst(e)ine-has been receiving increasing attention. Becau
se GSH is relatively more auto-oxidation resistant and stable than cyst(e)i
ne (CYSH), it serves as the preferred form for storage and transport of the
latter, especially in the extracellular and relatively much less reduced (
than intracellular) milieu, where CYSH oxidizes to cystine (CYSS) rapidly.
Over the past two decades, significant work has been going on to delineate
the intra- and extrahepatic (interorgan) turnover transport, and disposal o
f GSH and define the quantitative role of these processes in interorgan hom
eostasis of GSH, CYSH, and CYSS. These studies have identified the liver as
the central organ of interorgan GSH homeostasis, with sinusoidal GSH efflu
x as the major determinant of plasma GSH, CYSH, CYSS, and thiol-disulfide s
tatus of plasma. This article focuses on the principal components and deter
minants of interorgan homeostasis of GSH and its breakdown products. It als
o presents the current state of knowledge under both normal and diseased st
ates.