The Lathyrus excitotoxin beta-N-oxalyl-L-alpha,beta-diaminopropionic acid is a substrate of the L-cystine/L-glutamate exchanger system xc-.

Beta-N-oxalyl-L-alpha-beta-diaminopropionic acid (beta-L-ODAP) is an unusual amino acid present in seeds of plants from the Lathyrus genus that is generally accepted as the causative agent underlying the motor neuron degeneration and spastic paraparesis in human neurolathyrism. Much of the neuropathology produced by beta-L-ODAP appears to be a direct consequence of its structural similarities to the excitatory neurotransmitter L-glutamate and its ability to induce excitotoxicity as an agonist of non-NMDA receptors. Its actions within the CNS are, however, not limited to non-NMDA receptors, raising the likely possibility that the anatomical and cellular specificity of the neuronal damage observed in neurolathyrism may result from the cumulative activity of beta-L-ODAP at multiple sites.

Differentiation of substrate and non-substrate inhibitors of transport system xc(-): an obligate exchanger of L-glutamate and L-cystine.

In addition to the well-characterized sodium-dependent excitatory amino acid transporters (EAATs) present in the mammalian CNS, a chloride-dependent, sodium-independent transporter has also been identified that is capable of mediating the uptake of L-glutamate. Named system x(c)(-), this transporter is an obligate exchanger that normally couples the export of intracellular L-glutamate with the import of extracellular L-cystine. Two cell lines that express high levels of system x(c)(-) are used to delineate the pharmacology of the transporter and demonstrate that it is distinct from both the EAATs and EAA ionotropic receptors.