Journal
AMINO ACIDS
Volume 42, Issue 1, Pages 199-205Publisher
SPRINGER WIEN
DOI: 10.1007/s00726-011-0864-8
Keywords
Transsulfuration; Brain; Astrocyte; Cysteine; Cystathionine-gamma-lyase; Cystathionine-beta-synthase; Glutathione
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Funding
- Science Foundation Ireland
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Astrocyte cells require cysteine as a substrate for glutamate cysteine ligase (gamma-glutamylcysteine synthase; EC 6.3.2.2) catalyst of the rate-limiting step of the gamma-glutamylcycle leading to formation of glutathione (l-gamma-glutamyl-l-cysteinyl-glycine; GSH). In both astrocytes and glioblastoma/astrocytoma cells, the majority of cysteine originates from reduction of cystine imported by the x (c) (-) cystine-glutamate exchanger. However, the transsulfuration pathway, which supplies cysteine from the indispensable amino acid, methionine, has recently been identified as a significant contributor to GSH synthesis in astrocytes. The purpose of this review is to evaluate the importance of the transsulfuration pathway in these cells, particularly in the context of a reserve pathway that channels methionine towards cysteine when the demand for glutathione is high, or under conditions in which the supply of cystine by the x (c) (-) exchanger may be compromised.
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