Glutathione (GSH)

Story

Connected to · 2

cofactor · 1

N-Acetylcysteine
Glutathione (GSH) is a small molecule made of three amino acids, and the middle one, cysteine, is the scarcest, setting the pace of synthesis. N-acetylcysteine (NAC) releases cysteine inside the cell, giving the rate-limiting enzyme of the first step (GCL) material to work with, which makes NAC a raw-material supply for the glutathione production line.
Mechanism · 3
Mechanism · Why cysteine is the bottleneck
Glutathione is made of three amino acids: glutamate, cysteine and glycine. The middle one, cysteine, is in shortest supply, and the first step of synthesis is carried out by glutamate-cysteine ligase (GCL), the rate-limiting valve. Inside the cell NAC sheds its acetyl group and releases cysteine, giving that valve material to work with. The Lu 2013 review covers this synthesis route; Forman 2009 covers how glutathione is made, used and restored again, forming a protective cycle.
Safety · Emergency doses are not supplement doses
Both papers are reviews of synthesis and protective mechanisms, and neither sets a daily milligram dose for capsules on the shelf. Hospital use of intravenous NAC to treat acetaminophen overdose is an emergency treatment and must not be read as a dose for everyday supplements. What you can take away is where NAC sits: cysteine is the rate-limiting raw material, and NAC is its more stable precursor.
Myth · Swallowing glutathione capsules
Rebuilding glutathione stores with NAC after an acetaminophen overdose is an emergency treatment, not a shelf detox. Swallowing glutathione capsules does not get around the limit set by the synthesis step. People with particular conditions, such as G6PD deficiency, should ask a doctor before using NAC, and an antioxidant capsule is not the same as anti-aging.

regulates · 1

Milk Thistle
In cell and animal studies, silybin partly restores depleted glutathione; but after it is swallowed, very little reaches the blood, and most of what does is in conjugated form, so whether this step can happen in a person is an open question.

Read full story

Stop 1/6

An antioxidant cells make themselves

EVIDENCEREVIEW 2

READ THE ORIGINAL

Glutathione (GSH) is a small antioxidant molecule that almost every cell makes for itself in its cytoplasm. It is three amino acids strung together, a tripeptide: glutamate, cysteine and glycine. You do not need to eat it whole from food.

Of the three building blocks, only cysteine is the bottleneck: there is not much of it in the diet to begin with, and when a cell is busy dealing with oxidation or detoxification, a lot of it gets used up. The first step in making GSH is carried out by glutamate-cysteine ligase (GCL), the rate-limiting valve of the whole assembly line, and its speed is set by how much cysteine is inside the cell. So whatever can reliably supply cysteine is what decides how much GSH a cell can make.

An overdose of paracetamol (acetaminophen) drains the liver's GSH. If you suspect an overdose, get medical care immediately, even if there are no symptoms yet.

Educational content, not medical advice — consult a clinician.

Back