Analysis of BMAA enantiomers in cycads, cyanobacteria, and mammals: in vivo formation and toxicity of D-BMAA.
Document Type
Article
Publication Date
8-1-2017
JAX Location
Reprint Collection
JAX Source
Amino Acids 2017 Aug; 49(8):1427-1439.
Volume
49
Issue
8
First Page
1427
Last Page
1439
ISSN
1438-2199
PMID
28620737
DOI
https://doi.org/10.1007/s00726-017-2445-y
Abstract
Chronic dietary exposure to the cyanobacterial toxin β-N-methylamino-L-alanine (BMAA) triggers neuropathology in non-human primates, providing support for the theory that BMAA causes a fatal neurodegenerative illness among the indigenous Chamorro people of Guam. However, since there are two stereoisomers of BMAA, it is important to know if both can occur in nature, and if so, what role they might play in disease causation. As a first step, we analysed both BMAA enantiomers in cyanobacteria, cycads, and in mammals orally dosed with L-BMAA, to determine if enantiomeric changes could occur in vivo. BMAA in cyanobacteria and cycads was found only as the L-enantiomer. However, while the L-enantiomer in mammals was little changed after digestion, we detected a small pool of D-BMAA in the liver (12.5%) of mice and in the blood plasma of vervets (3.6%). Chiral analysis of cerebrospinal fluid of vervets and hindbrain of mice showed that the free BMAA in the central nervous system was the D-enantiomer. In vitro toxicity investigations with D-BMAA showed toxicity, mediated through AMPA rather than NMDA receptors. These findings raise important considerations concerning the neurotoxicity of BMAA and its relationship to neurodegenerative disease. Amino Acids 2017 Aug; 49(8):1427-1439.
Recommended Citation
Metcalf J,
Lobner D,
Banack S,
Cox GA,
Nunn P,
Wyatt P,
Cox P.
Analysis of BMAA enantiomers in cycads, cyanobacteria, and mammals: in vivo formation and toxicity of D-BMAA. Amino Acids 2017 Aug; 49(8):1427-1439.