GrxSSG

GrxSSG is the notation for the glutathionylated form of glutaredoxin, representing a mixed disulfide between the active-site cysteine of glutaredoxin (Grx) and glutathione (GSH). It is a transient intermediate formed during redox reactions in which glutaredoxin participates in protein deglutathionylation or S-glutathionylation.

Glutaredoxins are small thiol-disulfide oxidoreductases that help maintain redox homeostasis by catalyzing the reversible S-glutathionylation of proteins and by reducing protein disulfides with the help of GSH. In the catalytic cycle, Grx can form GrxSSG as an intermediate, either when Grx donates a reducing equivalent to a substrate or when a substrate is glutathionylated, and the Grx itself becomes mixed disulfide with GSH.

The GrxSSG intermediate is usually resolved by a reductant, such as another molecule of GSH or the thioredoxin system, which restores reduced Grx and regenerates GSSG or GSH. This transient state is of interest because its accumulation reflects the cellular redox state and the activity of the glutathione system.

In research, GrxSSG is used as a diagnostic or mechanistic indicator of S-glutathionylation dynamics, redox signaling, and oxidative stress responses. Studies employ biochemical assays and mass spectrometry to detect GrxSSG and monitor the cyclical redox reactions in which Grx participates.