Glutathione is the shortest true peptide in this catalogue: three residues, 307.3 g/mol, written γ-Glu-Cys-Gly. The Greek letter is not decoration. It records that the first peptide bond is made through the wrong carboxyl — the one on glutamate's side chain, not the one on its backbone — and that single fact explains most of what is unusual about the molecule.
The second thing worth knowing is about its one sulfur atom. It belongs to the cysteine and it is a free thiol, and a free thiol would rather be half of a disulfide. Two molecules of glutathione oxidise into one molecule of glutathione disulfide, which is a different compound with a different mass, and a vial labelled as the reduced form is always, slowly, on its way to becoming the oxidised one.
- Reduced glutathione (GSH): C10H17N3O6S, 307.3 g/mol, CAS 70-18-8 (PubChem CID 124886).
- γ-Glu-Cys-Gly — the glutamate is joined through its side-chain carboxyl, which ordinary peptidases do not cleave.
- The single sulfur is a free thiol on the cysteine; there is no disulfide bridge inside the molecule.
- Two GSH oxidise to one glutathione disulfide (GSSG): C20H32N6O12S2, 612.6 g/mol (PubChem CID 65359) — two molecules minus two hydrogens.
- A certificate for this compound has to say how much is reduced and how much is already the dimer; a purity percentage alone does not.
What the γ records
Glutamate has two carboxyl groups: one on its backbone, the α-carboxyl every amino acid has, and one at the end of its side chain, the γ-carboxyl. A normal peptide bond to glutamate uses the α-carboxyl. In glutathione the cysteine is attached to the γ-carboxyl instead, which leaves glutamate's α-carboxyl free and its α-amine free — the molecule has, in effect, a whole amino acid hanging off one end by its side chain.
The consequence is practical. The enzymes that take peptides apart — peptidases — recognise α-peptide bonds, and this one is not one. Ordinary peptidases leave the γ-glutamyl bond alone; a separate enzyme class, the γ-glutamyl transpeptidases, exists to handle it. That is why a three-residue peptide survives where a three-residue peptide ought not to, and it is a property of the bond, not of any claim.
One sulfur, and what it does with itself
The formula C10H17N3O6S carries exactly one sulfur, on the cysteine, as a thiol — an S–H group. Thiols oxidise: two of them give up a hydrogen each and join through their sulfurs to form a disulfide, S–S. Do that to two glutathione molecules and the product is one molecule of glutathione disulfide, GSSG.
The arithmetic is checkable from the two formulas. Twice C10H17N3O6S is C20H34N6O12S2; remove the two hydrogens lost in forming the S–S bond and it is C20H32N6O12S2, which is GSSG. In mass: 2 × 307.32 = 614.64, minus 2 × 1.008 = 612.62 — PubChem lists GSSG at 612.6. Nothing has been added; two molecules have become one and lost two hydrogens between them.
