cystine:glutamate antiporter activity

Definition

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.'
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Proteins (1)

Compounds (9)