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Molecular mechanisms of cystine transport.

Biochemical Society transactions (2001-11-16)
G J McBean, J Flynn
ABSTRACT

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 L-cystine 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 L-cystine transport is by a low-affinity, sodium-dependent mechanism (K(m)=473+/-146 microM), that is mediated by the X(AG)- family of glutamate transporters. Both L-glutamate (IC(50)=9.1+/-0.4 microM) and L-cysteine sulphinate (IC(50)=16.4+/-3.6 microM) are non-competitive inhibitors of sodium-dependent L-[(14)C]cystine transport, whereas L-trans-pyrrolidine-2,4-dicarboxylic acid (IC(50)=5.6+/-2.0 microM), L-serine-O-sulphate (IC(50)=13.2+/-5.4 microM), kainate (IC(50)=215+/-78 microM) and L-cysteine (IC(50)=363+/-63 microM) are competitive inhibitors. L-Cystine has no effect on the sodium-dependent uptake of D-[(3)H]aspartate. These results suggest that L-cystine binds to a site that is different from the L-glutamate recognition site on X(AG)- glutamate transporters. In rat brain slices, sodium-dependent transport of both L-glutamate and L-cystine is necessary for maintaining glutathione levels. Uptake of L-cystine is sensitive to inhibition by an increased extracellular concentration of L-glutamate, which has important implications for understanding conditions that may initiate oxidative stress.

MATERIALS
Product Number
Brand
Product Description

Supelco
L-Cystine, certified reference material, TraceCERT®, Manufactured by: Sigma-Aldrich Production GmbH, Switzerland
Sigma-Aldrich
L-Cystine, from non-animal source, meets EP testing specifications, suitable for cell culture, 98.5-101.0%
Sigma-Aldrich
L-Cystine, ≥98% (TLC), crystalline
Cystine, European Pharmacopoeia (EP) Reference Standard
Sigma-Aldrich
L-Cystine, produced by Wacker Chemie AG, Burghausen, Germany, ≥98.5%
SAFC
L-Cystine
Supelco
L-Cystine, Pharmaceutical Secondary Standard; Certified Reference Material