Glutathione

Glutathione is γ-Glu-Cys-Gly. The gamma linkage — formed through glutamate's side chain rather than its alpha carboxyl — is unusual in biology and protects the molecule from the peptidases that would otherwise degrade it, which is how it sustains millimolar intracellular concentrations.

The reactive part is the cysteine thiol. Two glutathione molecules oxidise to a disulfide-linked dimer (GSSG) and are reduced back by glutathione reductase, and that cycle is the buffer against which cellular redox is measured.

• Direct scavenging of reactive oxygen and nitrogen species

• Cofactor for glutathione peroxidase, reducing hydrogen peroxide and lipid peroxides

• Phase II conjugation, where glutathione S-transferases attach it to xenobiotics for excretion — the basis of much toxicology

• Protein S-glutathionylation, a reversible post-translational modification with signalling roles

• GSH:GSSG ratio, the standard readout of oxidative status

The recurring practical problem is delivery: exogenous glutathione is poorly taken up by cells, which is why much of the applied literature concerns precursors such as N-acetylcysteine rather than the tripeptide itself.

NAD+ is the other major redox cofactor and faces the same delivery question. SS-31 addresses oxidative stress at its mitochondrial source rather than by buffering.