Beta-N-methylaminoalanine (BMAA): metabolism and metabolic effects in model systems and in neural and other tissues of the rat in vitro.
The non-protein amino acid, beta-N-methylaminoalanine (BMAA), is neurotoxic and has been implicated in the amyotrophic lateral sclerosis-Parkinsonism-dementia (ALS-PD) complex of Guam. This concept remains controversial, in part because of the lack of a convincing animal model. The neuropharmacology of BMAA is well established, but little is known of its metabolism. This paper reports aspects of the metabolism, and metabolic effects, of BMAA in rat tissues. BMAA changed the distribution of taurine, glycine and serine between rat brain slices and their incubation medium; the glutamate/glutamine cycle between neurones and glia was also compromised. In model experiments BMAA reacted non-enzymatically with pyridoxal-5'-phosphate, releasing methylamine. Rat liver and kidney homogenates, but not brain homogenates, also formed methylamine and 2,3-diaminopropanoic acid when incubated with BMAA. These results provide evidence that several biochemical mechanisms are involved in the neurotoxicity of BMAA. The novel discovery that methylamine is formed from BMAA in rat liver and kidney preparations may be significant since chronic administration of methylamine to rats causes oxidative stress. The extent to which this reaction occurs in different animal species might be a decisive factor in selecting an animal model.
Nunn
Peter B
PB
School of Pharmacy and Biomedical Sciences, University of Portsmouth, St. Michael's Building, White Swan Road, Portsmouth PO1 2DT, UK. peter.nunn@port.ac.uk
Ponnusamy
Malarvizhi
M
D000596:Amino Acids / Q000032:analysis / Q000378:metabolism; D000599:Amino Acids, Diamino / Q000378:metabolism* / Q000633:toxicity*; D000600:Amino Acids, Dicarboxylic / Q000378:metabolism* / Q000633:toxicity*; D000818:Animals; D001923:Brain Chemistry / Q000187:drug effects; D066298:In Vitro Techniques; D007668:Kidney / Q000187:drug effects / Q000378:metabolism; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D009420:Nervous System / Q000187:drug effects* / Q000378:metabolism; D018384:Oxidative Stress; D011732:Pyridoxal Phosphate / Q000633:toxicity; D051381:Rats; D017207:Rats, Sprague-Dawley
D000596:Amino Acids; D000599:Amino Acids, Diamino; D000600:Amino Acids, Dicarboxylic; C064614:beta-(N-carboxy-N-methyl)aminoalanine; D011732:Pyridoxal Phosphate