title: Equilibrium Dynamics of β-N-Methylamino-L-Alanine (BMAA) and Its Carbamate Adducts at Physiological Conditions.
abstract: Elevated incidences of Amyotrophic Lateral Sclerosis/Parkinsonism Dementia complex (ALS/PDC) is associated with β-methylamino-L-alanine (BMAA), a non-protein amino acid. In particular, the native Chamorro people living in the island of Guam were exposed to BMAA by consuming a diet based on the cycad seeds. Carbamylated forms of BMAA are glutamate analogues. The mechanism of neurotoxicity of the BMAA is not completely understood, and BMAA acting as a glutamate receptor agonist may lead to excitotoxicity that interferes with glutamate transport systems. Though the interaction of BMAA with bicarbonate is known to produce carbamate adducts, here we demonstrate that BMAA and its primary and secondary adducts coexist in solution and undergoes a chemical exchange among them. Furthermore, we determined the rates of formation/cleavage of the carbamate adducts under equilibrium conditions using two-dimensional proton exchange NMR spectroscopy (EXSY). The coexistence of the multiple forms of BMAA at physiological conditions adds to the complexity of the mechanisms by which BMAA functions as a neurotoxin.
authors: Department of Chemistry, College of Science and Mathematics, California State University, Fresno, California, 93740, United States of America.
authors: David
authors: D
authors: Zimmerman
authors: Department of Chemistry, College of Science and Mathematics, California State University, Fresno, California, 93740, United States of America.
authors: Joy J
authors: JJ
authors: Goto
authors: Department of Chemistry, College of Science and Mathematics, California State University, Fresno, California, 93740, United States of America.|Department of Medical Pathology and Laboratory Medicine, University of California Davis School of Medicine, Sacramento, California, 95817, United States of America.
authors: Viswanathan V
authors: VV
authors: Krishnan
mesh_terms: D000599:Amino Acids, Diamino / Q000737:chemistry / Q000378:metabolism*; D001692:Biological Transport; D002219:Carbamates / Q000737:chemistry / Q000378:metabolism*; D000087522:Cyanobacteria Toxins; D018698:Glutamic Acid / Q000378:metabolism; D007700:Kinetics; D008968:Molecular Conformation; D009498:Neurotoxins / Q000737:chemistry / Q000378:metabolism*; D019906:Nuclear Magnetic Resonance, Biomolecular
chemical_list: D000599:Amino Acids, Diamino; D002219:Carbamates; D000087522:Cyanobacteria Toxins; D009498:Neurotoxins; C001824:beta-N-methylamino-L-alanine; D018698:Glutamic Acid