Target type: molecularfunction
Enables the transfer of a solute or solutes from one side of a membrane to the other according to the reaction: cystine(out) + glutamate(in) = cystine(in) + glutamate(out). [TC:2.A.3.8.5]
Cystine:glutamate antiporter activity is a specialized transmembrane transport mechanism that facilitates the exchange of cystine (a disulfide-bonded dimer of cysteine) and glutamate across cell membranes. This process is crucial for maintaining cellular redox homeostasis, cysteine supply, and glutamate neurotransmission.
Cystine, an oxidized form of cysteine, is essential for the synthesis of glutathione, a key antioxidant that protects cells from oxidative stress. However, cystine is poorly permeable across cell membranes. The cystine:glutamate antiporter, also known as the system x(c)- transporter, overcomes this barrier by coupling the inward transport of cystine with the outward transport of glutamate. This co-transport mechanism is driven by the electrochemical gradient of glutamate, which is typically higher inside the cell.
The antiporter is composed of two subunits: xCT, a light chain that mediates the transport of cystine and glutamate, and 4F2hc, a heavy chain that anchors the transporter to the cell membrane and provides stability.
Here's a detailed breakdown of the molecular function:
1. **Binding of Cystine and Glutamate:** The transporter has separate binding sites for cystine and glutamate on the extracellular and intracellular faces of the cell membrane, respectively.
2. **Conformational Change:** Binding of cystine and glutamate induces a conformational change in the transporter, facilitating their simultaneous translocation across the membrane.
3. **Exchange Mechanism:** The antiporter operates in a 1:1 stoichiometry, meaning that one molecule of cystine is exchanged for one molecule of glutamate. This ensures that the net movement of charge across the membrane remains balanced.
4. **Redox Homeostasis:** The uptake of cystine is vital for maintaining cellular redox homeostasis. Cystine is reduced to cysteine, which is then utilized for glutathione synthesis. Glutathione acts as a reducing agent, neutralizing reactive oxygen species (ROS) and protecting cells from oxidative damage.
5. **Cysteine Supply:** The antiporter provides a major source of cysteine for protein synthesis and other metabolic processes. Cysteine is an essential amino acid that cannot be synthesized by humans and must be obtained from the diet.
6. **Glutamate Neurotransmission:** Glutamate is the primary excitatory neurotransmitter in the central nervous system. The release of glutamate from neurons is crucial for synaptic plasticity, learning, and memory. The cystine:glutamate antiporter plays a role in regulating glutamate levels in the extracellular space, ensuring proper neuronal function.
Overall, the cystine:glutamate antiporter is a critical membrane transport system that plays a multifaceted role in cellular physiology, including redox homeostasis, cysteine supply, and glutamate neurotransmission.'
"
Protein | Definition | Taxonomy |
---|---|---|
Cystine/glutamate transporter | A cystine/glutamate transporter that is encoded in the genome of human. [PRO:DNx, UniProtKB:Q9UPY5] | Homo sapiens (human) |
Compound | Definition | Classes | Roles |
---|---|---|---|
mesalamine | mesalamine : A monohydroxybenzoic acid that is salicylic acid substituted by an amino group at the 5-position. Mesalamine: An anti-inflammatory agent, structurally related to the SALICYLATES, which is active in INFLAMMATORY BOWEL DISEASE. It is considered to be the active moiety of SULPHASALAZINE. (From Martindale, The Extra Pharmacopoeia, 30th ed) | amino acid; aromatic amine; monocarboxylic acid; monohydroxybenzoic acid; phenols | non-steroidal anti-inflammatory drug |
sulfapyridine | sulfapyridine : A sulfonamide consisting of pyridine with a 4-aminobenzenesulfonamido group at the 2-position. Sulfapyridine: Antibacterial, potentially toxic, used to treat certain skin diseases. | pyridines; substituted aniline; sulfonamide; sulfonamide antibiotic | antiinfective agent; dermatologic drug; drug allergen; environmental contaminant; xenobiotic |
sulfasalazine | sulfasalazine : An azobenzene consisting of diphenyldiazene having a carboxy substituent at the 4-position, a hydroxy substituent at the 3-position and a 2-pyridylaminosulphonyl substituent at the 4'-position. Sulfasalazine: A drug that is used in the management of inflammatory bowel diseases. Its activity is generally considered to lie in its metabolic breakdown product, 5-aminosalicylic acid (see MESALAMINE) released in the colon. (From Martindale, The Extra Pharmacopoeia, 30th ed, p907) | ||
cysteine | cysteine; cysteine zwitterion; L-alpha-amino acid; proteinogenic amino acid; serine family amino acid | EC 4.3.1.3 (histidine ammonia-lyase) inhibitor; flour treatment agent; human metabolite | |
quisqualic acid | Quisqualic Acid: An agonist at two subsets of excitatory amino acid receptors, ionotropic receptors that directly control membrane channels and metabotropic receptors that indirectly mediate calcium mobilization from intracellular stores. The compound is obtained from the seeds and fruit of Quisqualis chinensis. | non-proteinogenic alpha-amino acid | |
serine o-sulfate | L-serine O-sulfate : A non-proteinogenic L-alpha-amino acid that is the O-sulfo derivative of L-serine. serine O-sulfate: RN given refers to (L)-isomer | L-serine derivative; non-proteinogenic L-alpha-amino acid; O-sulfoamino acid | |
homocysteic acid | homocysteic acid : A non-proteinogenic alpha-amino acid that is homocysteine in which the thiol group has benn oxidised to the corresponding sulfonic acid. homocysteic acid: promotes growth in hypophysectomized rats; RN given refers to parent cpd L-homocysteic acid : A homocysteic acid with L-configuration. | homocysteic acid | NMDA receptor agonist |
susalimod | susalimod: analogue of sulphasalazine, was designed for use in the treatment of rheumatoid arthritis | ||
erastin | erastin : A member of the class of quinazolines that is quinazolin-4(3H)-one in which the hydrogens at positions 2 and 3 are replaced by 1-{4-[(4-chlorophenoxy)acetyl]piperazin-1-yl}ethyl and 2-ethoxyphenyl groups, respectively. It is an inhibitor of voltage-dependent anion-selective channels (VDAC2 and VDAC3) and a potent ferroptosis inducer. erastin: an antineoplastic agent; structure in first source | aromatic ether; diether; monochlorobenzenes; N-acylpiperazine; N-alkylpiperazine; quinazolines; tertiary carboxamide | antineoplastic agent; ferroptosis inducer; voltage-dependent anion channel inhibitor |