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The transsulfuration pathway: a source of cysteine for glutathione in astrocytes

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Abstract

Astrocyte cells require cysteine as a substrate for glutamate cysteine ligase (γ-glutamylcysteine synthase; EC 6.3.2.2) catalyst of the rate-limiting step of the γ-glutamylcycle leading to formation of glutathione (l-γ-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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Abbreviations

GSH:

l-γ-glutamyl-l-cysteinyl-glycine (glutathione)

GSSG:

Oxidised form of glutathione

DEM:

Diethylmaleate

H2S:

Hydrogen sulfide

IL-6:

Interleukin-6

JNK:

c-Jun-N-terminal kinase

MAPK:

Mitogen-activated protein kinase

NF-κB:

Nuclear factorκB

SAPK:

Stress-activated protein kinase

TNFα:

Tumour necrosis factorα

xCT:

Subunit of the x −c cystine-glutamate exchanger

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Acknowledgments

The author’s research in this area is supported by Science Foundation Ireland.

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Authors and Affiliations

  1. UCD School of Biomolecular and Biomedical Science, Conway Institute, University College, Dublin 4, Ireland

    Gethin J. McBean

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Correspondence to Gethin J. McBean.

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McBean, G.J. The transsulfuration pathway: a source of cysteine for glutathione in astrocytes. Amino Acids 42, 199–205 (2012). https://doi.org/10.1007/s00726-011-0864-8

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  • DOI: https://doi.org/10.1007/s00726-011-0864-8

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