Glutamate
Glutamate is an amino acid and one of glutathione's three building blocks, joined to cysteine in the first step of glutathione synthesis. Cells get it from food, from other amino acids and from glutamine.
Also called glutamic acid, L-glutamate, Glu.
Glutathione attaches glutamate in an unusual way, through its side-chain (gamma) carboxyl group rather than the usual peptide link, which is why glutathione's chemical name begins gamma-glutamyl. That bond resists ordinary protein-digesting enzymes but not gamma-glutamyltransferase, the enzyme that breaks down swallowed glutathione in the gut and liver (Witschi 1992).
Glutamate cysteine ligase joins glutamate to cysteine in the rate-limiting first step (Lu 2013). In cartilage cells, glutamine is a major source: glutaminase converts it to glutamate, and glutathione made from glutamine helped growth-plate chondrocytes keep reactive oxygen species down (Stegen 2020).
Glutamate also affects cysteine supply. One of the cell's cystine transporters, the xc- system, swaps glutamate out for cystine in, and it is inhibited by glutamate (Han 1997).
Sources
- Witschi A, Reddy S, Stofer B et al. The systemic availability of oral glutathione. Eur J Clin Pharmacol 1992.
- Lu SC. Glutathione synthesis. Biochim Biophys Acta 2013.
- Stegen S, Rinaldi G, Loopmans S et al. Glutamine Metabolism Controls Chondrocyte Identity and Function. Dev Cell 2020.
- Han D, Handelman G, Marcocci L et al. Lipoic acid increases de novo synthesis of cellular glutathione by improving cystine utilization. Biofactors 1997.
Related terms
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