Enzymes
| UniProtKB help_outline | 1,143 proteins |
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- Name help_outline L-cystine Identifier CHEBI:35491 (Beilstein: 1888247) help_outline Charge 0 Formula C6H12N2O4S2 InChIKeyhelp_outline LEVWYRKDKASIDU-IMJSIDKUSA-N SMILEShelp_outline [NH3+][C@@H](CSSC[C@H]([NH3+])C([O-])=O)C([O-])=O 2D coordinates Mol file for the small molecule Search links Involved in 14 reaction(s) Find molecules that contain or resemble this structure Find proteins in UniProtKB for this molecule
- Name help_outline L-glutamate Identifier CHEBI:29985 (CAS: 11070-68-1) help_outline Charge -1 Formula C5H8NO4 InChIKeyhelp_outline WHUUTDBJXJRKMK-VKHMYHEASA-M SMILEShelp_outline [NH3+][C@@H](CCC([O-])=O)C([O-])=O 2D coordinates Mol file for the small molecule Search links Involved in 249 reaction(s) Find molecules that contain or resemble this structure Find proteins in UniProtKB for this molecule
Cross-references
| RHEA:70995 | RHEA:70996 | RHEA:70997 | RHEA:70998 | |
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| Reaction direction help_outline | undefined | left-to-right | right-to-left | bidirectional |
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| MetaCyc help_outline |
Publications
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Cloning and expression of a plasma membrane cystine/glutamate exchange transporter composed of two distinct proteins.
Sato H., Tamba M., Ishii T., Bannai S.
Transport system xc-found in plasma membrane of cultured mammalian cells is an exchange agency for anionic amino acids with high specificity for anionic form of cystine and glutamate. We have isolated cDNA encoding the transporter for system xc-from mouse activated macrophages by expression in Xen ... >> More
Transport system xc-found in plasma membrane of cultured mammalian cells is an exchange agency for anionic amino acids with high specificity for anionic form of cystine and glutamate. We have isolated cDNA encoding the transporter for system xc-from mouse activated macrophages by expression in Xenopus oocytes. The expression of system xc-activity in oocytes required two cDNA transcripts, and the sequence analysis revealed that one is identical with the heavy chain of 4F2 cell surface antigen (4F2hc) and the other is a novel protein of 502 amino acids with 12 putative transmembrane domains. The latter protein, named xCT, showed a significant homology with those recently reported to mediate cationic or zwitterionic amino acid transport when co-expressed with 4F2hc. Thus xCT is a new member of a family of amino acid transporters that form heteromultimeric complex with 4F2hc, with a striking difference in substrate specificity. The expression of system xc-was highly regulated, and Northern blot analysis demonstrated that the expression of both 4F2hc and xCT was enhanced in macrophages stimulated by lipopolysaccharide or an electrophilic agent. However, the expression of xCT was more directly correlated with the system xc- activity. << Less
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N-acetylcysteine, xCT and suppression of Maxi-chloride channel activity in human placenta.
Lofthouse E.M., Manousopoulou A., Cleal J.K., O'Kelly I.M., Poore K.R., Garbis S.D., Lewis R.M.
<h4>Introduction</h4>Placental oxidative stress features in pregnancy pathologies but in clinical trials antioxidant supplementation has not improved outcomes. N-acetylcysteine (NAC) stimulates glutathione production and is proposed as a therapeutic agent in pregnancy. However, key elements of N-a ... >> More
<h4>Introduction</h4>Placental oxidative stress features in pregnancy pathologies but in clinical trials antioxidant supplementation has not improved outcomes. N-acetylcysteine (NAC) stimulates glutathione production and is proposed as a therapeutic agent in pregnancy. However, key elements of N-acetylcysteine biology, including its cellular uptake mechanism, remains unclear. This study explores how the cystine/glutamate transporter xCT may mediate N-acetylcysteine uptake and how N-acetylcysteine alters placental redox status.<h4>Methods</h4>The involvement of xCT in NAC uptake by the human placenta was studied in perfused placenta and Xenopus oocytes. The effect of short-term N-acetylcysteine exposure on the placental villous proteome was determined using LC-MS. The effect of N-acetylcysteine on Maxi-chloride channel activity was investigated in perfused placenta, villous fragments and cell culture.<h4>Results</h4>Maternoplacental N-acetylcysteine administration stimulated intracellular glutamate efflux suggesting a role of the exchange transporter xCT, which was localised to the microvillous membrane of the placental syncytiotrophoblast. Placental exposure to a bolus of N-acetylcysteine inhibited subsequent activation of the redox sensitive Maxi-chloride channel independently of glutathione synthesis. Stable isotope quantitative proteomics of placental villi treated with N-acetylcysteine demonstrated changes in pathways associated with oxidative stress, apoptosis and the acute phase response.<h4>Discussion</h4>This study suggests that xCT mediates N-acetylcysteine uptake into the placenta and that N-acetylcysteine treatment of placental tissue alters the placental proteome while regulating the redox sensitive Maxi-chloride channel. Interestingly N-acetylcysteine had antioxidant effects independent of the glutathione pathway. Effective placental antioxidant therapy in pregnancy may require maintaining the balance between normalising redox status without inhibiting physiological redox signalling. << Less
Placenta 110:46-55(2021) [PubMed] [EuropePMC]
This publication is cited by 1 other entry.