The transport of l-cystine into cells of the mammalian brain is an essential step in the supply of cysteine for synthesis of the antioxidant glutathione. Uptake of lcystine in rat brain synaptosomes occurs by three mechanisms that are distinguishable on the basis of their ionic dependence, kinetics of transport and specificity of inhibitors. Almost 90°% of lcystine transport is by a low-affinity, sodium-dependent mechanism (Km = 473 ± 146 μM), that is mediated by the XAG-family of glutamate transporters. Both lglutamate (IC50 = 9.1 ± 0.4 μM) and lcysteine sulphinate (IC50 = 16.4 ± 3.6 μM) are non-competitive inhibitors of sodium-dependent l[14C]cystine transport, whereas ltrans-pyrrolidine-2,4-dicarboxylic acid (IC50 = 5.6 ± 2.0 μM), lserine-O-sulphate (IC50 = 13.2 ± 5.4 μM), kainate (IC50 = 215 ± 78 μM) and lcysteine (IC50 = 363 ± 63 μM) are competitive inhibitors. lCystine has no effect on the sodium-dependent uptake of D-[3H]aspartate. These results suggest that lcystine binds to a site that is different from the lglutamate recognition site on XAG-glutamate transporters. In rat brain slices, sodium-dependent transport of both lglutamate and lcystine is necessary for maintaining glutathione levels. Uptake of lcystine is sensitive to inhibition by an increased extracellular concentration of lglutamate, which has important implications for understanding conditions that may initiate oxidative stress.
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Conference Article|
November 01 2001
Molecular mechanisms of cystine transport
G. J. McBean;
G. J. McBean
1
1Department of Biochemistry, Conway Institute of Biomolecular and Biomedical Research, University College Dublin, Dublin 4, Ireland
1To whom correspondence should be addressed (e-mail gethin.mcbean@ucd.ie).
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J. Flynn
J. Flynn
1Department of Biochemistry, Conway Institute of Biomolecular and Biomedical Research, University College Dublin, Dublin 4, Ireland
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Publisher: Portland Press Ltd
Received:
May 31 2001
Online ISSN: 1470-8752
Print ISSN: 0300-5127
© 2001 Biochemical Society
2001
Biochem Soc Trans (2001) 29 (6): 717–722.
Article history
Received:
May 31 2001
Citation
G. J. McBean, J. Flynn; Molecular mechanisms of cystine transport. Biochem Soc Trans 1 November 2001; 29 (6): 717–722. doi: https://doi.org/10.1042/bst0290717
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