Review: cysteine supply and one key enzyme control how fast cells make glutathione
This 2013 review explains how cells make glutathione. The two main controls on the process are the supply of cysteine, a sulphur-containing amino acid, and the activity of glutamate cysteine ligase, the first and rate-limiting enzyme in the pathway.
What they did
This is a review of published research, not a new experiment. The author summarised the main jobs of glutathione (GSH) in the body and the factors that control how cells make it, including diseases where that process goes wrong.
What they found
Glutathione is present in all mammalian tissues as the most abundant non-protein thiol, a sulphur-containing molecule, that defends against oxidative stress. It also takes part in redox signalling and in clearing foreign chemicals, and helps regulate cell growth, cell death, immune function and scarring.
Cells build glutathione in the cytosol, the fluid inside the cell, in two enzyme steps. The key controls are the availability of cysteine and the activity of the first enzyme, glutamate cysteine ligase (GCL), which has two parts. The second enzyme is GSH synthetase. These enzymes are regulated in several ways, often together, by factors including Nrf2, AP-1 and NF-kB.
The review lists conditions where faulty glutathione production appears to play a part, including diabetes, lung and liver fibrosis, alcohol-related liver disease and drug-resistant tumour cells.
What it can't tell us
This is a general review of glutathione biology. It does not discuss cartilage or joints, and it reports no new data. It describes how the pathway is controlled; it does not test whether eating more cysteine or any other building block changes glutathione in a particular tissue.
Why it matters
This is the standard reference for how glutathione is made. Its central point, that cysteine supply is one of the two main limits, is why so much research on raising glutathione focuses on providing its building blocks rather than glutathione itself. Cartilage cells, which have no blood vessels nearby, rely on this same pathway to make their own.
The paper
- Lu SC. Glutathione synthesis. Biochim Biophys Acta 2013.
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