Beta-N-methylamino-L-alanine neurotoxicity: requirement for bicarbonate as a cofactor.
Ingestion of the excitotoxic cycad seed amino acid beta-N-methylamino-L-alanine may be responsible for the neuronal degeneration associated with Guam amyotrophic lateral sclerosis-parkinsonism-dementia in man. However, the basis for the central neurotoxicity of beta-N-methylamino-L-alanine has been unclear, as it lacks the omega acidic (or equivalent electronegative) moiety characteristic of other excitatory amino acids. beta-N-methylamino-L-alanine produced neurotoxic and neuroexcitatory effects in murine cortical cell cultures only when physiological concentrations of bicarbonate were available in the extracellular bathing medium. Bicarbonate may interact noncovalently with beta-N-methylamino-L-alanine to produce, in combination, a molecular configuration that activates glutamate receptors.
D000599:Amino Acids, Diamino / Q000633:toxicity*; D000818:Animals; D001639:Bicarbonates / Q000378:metabolism*; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000187:drug effects*; D000087522:Cyanobacteria Toxins; D004594:Electrophysiology; D006863:Hydrogen-Ion Concentration; D051379:Mice; D008839:Microelectrodes; D009474:Neurons / Q000187:drug effects*; D010069:Oxadiazoles / Q000633:toxicity; D016318:Quisqualic Acid; D015091:beta-Alanine / Q000031:analogs & derivatives / Q000633:toxicity
D000599:Amino Acids, Diamino; D001639:Bicarbonates; D000087522:Cyanobacteria Toxins; D010069:Oxadiazoles; C001824:beta-N-methylamino-L-alanine; D015091:beta-Alanine; C100126:oxalyldiaminopropionic acid; D016318:Quisqualic Acid