What Is Glutathione? A Plain-English Chemistry Guide

Glutathione is one of the most-studied small molecules in biochemistry. It is also one of the most-searched compounds we carry.

At our small Michigan shop, we like to explain what a compound actually is. So this post sticks to chemistry: its structure, its two main forms, a bit of history, and how labs check what is in the vial.

What Is Glutathione?

Glutathione is a tripeptide. That means it is a short chain of three amino acids: glutamate, cysteine and glycine [1][2].

Its full chemical name is gamma-L-glutamyl-L-cysteinyl-glycine. It is often shortened to GSH. The "SH" stands for its thiol group, a sulfur atom bonded to a hydrogen atom [1][2].

Its molecular formula is C₁₀H₁₇N₃O₆S. Its average mass is about 307.33 Da, and its monoisotopic mass is 307.0838 Da [2]. (A dalton, or Da, is the unit chemists use for the mass of a molecule.)

What Makes Its Structure Unusual

In most peptides, amino acids link through the same spot on each one, called the alpha-carboxyl group. Glutathione is different.

Its glutamate links through its side chain instead. ChEBI describes it as glutamic acid "attached via its side chain to the N-terminus of cysteinylglycine" [2]. This side-chain link is called a gamma bond. It is why the name starts with "gamma-glutamyl," and it sets glutathione apart from an ordinary Glu-Cys-Gly peptide.

The Two Forms: GSH and GSSG

The cysteine in glutathione carries a thiol group (-SH). Two GSH molecules can each lose a hydrogen atom and join together. They connect through a sulfur-to-sulfur link called a disulfide bond [3].

The joined form is called glutathione disulfide, or GSSG. Chemists call GSH the "reduced" form and GSSG the "oxidized" form.

• GSH (reduced): C₁₀H₁₇N₃O₆S, monoisotopic mass 307.0838 Da [2]
• GSSG (oxidized): C₂₀H₃₂N₆O₁₂S₂, monoisotopic mass 612.1520 Da [3]

The math makes a handy check. Two GSH units add up to 614.1676 Da. GSSG is about 2.016 Da lighter, which is the mass of the two hydrogen atoms lost when the disulfide bond forms (calculated from the ChEBI values [2][3]).

Glutathione in Cell Chemistry

Biochemists describe glutathione as the most abundant small thiol compound made in cells [4]. "Small" here means a low molecular weight.

Researchers look at the balance between the GSH and GSSG forms to describe a cell's redox state. Redox simply means the balance of chemical reduction and oxidation. That is why labs often measure GSH and GSSG side by side [4][5].

A Short History

British biochemist Frederick Gowland Hopkins reported "an autoxidisable constituent of the cell" in the Biochemical Journal in 1921 [6]. He followed it with a 1925 paper simply titled "Glutathione" [7].

In 1929 he published "On Glutathione: A Reinvestigation" in the Journal of Biological Chemistry [8]. There he revisited his earlier work on the molecule's makeup.

Later, Alton Meister and Mary Anderson wrote a 1983 review in the Annual Review of Biochemistry. It is still a widely cited summary of glutathione chemistry [9].

How Labs Check Identity and Purity

Identity: mass spectrometry

Mass spectrometry (MS) is a tool that measures the mass of molecules. For glutathione, a lab looks for a signal at 307.08 Da for GSH and 612.15 Da for GSSG [2][3].

The two forms differ a lot in mass. So MS can tell them apart easily.

Purity: HPLC

High-performance liquid chromatography (HPLC) separates a sample into its parts. Published methods use simple HPLC setups to separate and detect GSH and GSSG in the same run [5].

A purity result tells you how much of the sample is the target compound.

Why air exposure matters for handling

GSH can turn into GSSG over time. Because of this, chemists stress careful sample preparation. Some add thiol-blocking agents, such as N-ethylmaleimide, to stop changes during testing [5].

For lab material, this is a good reason to keep containers sealed, cold, dry and away from air. It also helps to read any lab report with the GSH vs. GSSG question in mind.

About Our Glutathione

We carry the glutathione research compound for laboratory research. Documentation for each lot is available to verified purchasers.

Want more compound chemistry? Read What Is GHK-Cu? and What Is KPV?

FAQ

Is glutathione a peptide?

Yes. It is a tripeptide made of glutamate, cysteine and glycine. They are joined through an unusual gamma bond at the glutamate [1][2].

What is the difference between GSH and GSSG?

GSH is the reduced, single-molecule form with a free thiol group. GSSG is two GSH units joined by a disulfide bond. It is about 2 Da lighter than two GSH molecules combined [2][3].

What is glutathione's molecular weight?

About 307.33 g/mol for GSH and 612.64 g/mol for GSSG [2][3].

For laboratory research use only. Not for human or veterinary use.

Sources

1. PubChem: Glutathione (CID 124886)
2. ChEBI: glutathione (CHEBI:16856)
3. ChEBI: glutathione disulfide (CHEBI:17858)
4. Forman HJ, Zhang H, Rinna A. Molecular Aspects of Medicine, 2009;30(1-2):1-12. doi:10.1016/j.mam.2008.08.006
5. Yap LP, et al. Determination of GSH, GSSG, and GSNO using HPLC with electrochemical detection. Methods in Enzymology, 2010;473:137-47. doi:10.1016/S0076-6879(10)73006-8
6. Hopkins FG. On an Autoxidisable Constituent of the Cell. Biochemical Journal, 1921. doi:10.1042/bj0150286
7. Hopkins FG. Glutathione. Biochemical Journal, 1925. doi:10.1042/bj0190787
8. Hopkins FG. On Glutathione: A Reinvestigation. Journal of Biological Chemistry, 1929. doi:10.1016/S0021-9258(18)77062-2
9. Meister A, Anderson ME. Glutathione. Annual Review of Biochemistry, 1983. doi:10.1146/annurev.bi.52.070183.003431