Chiral analysis of β-methylamino alanine (BMAA) enantiomers after (+)-1-(9-fluorenyl)-ethyl chloroformate (FLEC) derivatization and LC-MS/MS

Abstract

A developed method for chiral analysis of neurotoxin β-methylamino alanine (BMAA) allowed detection of d-BMAA in cycad seed samples.

A Direct Analysis of β-N-methylamino-l-alanine Enantiomers and Isomers and Its Application to Cyanobacteria and Marine Mollusks

“…Analytical methods and laboratory equipment have progressed from fluorescence to mass spectrometric detection, with or without chemical derivatization to provide accurate and specific detection of these molecules [85]. Although such methods are useful for isolating and quantifying BMAA and its isomers, so far, methods to understand the enantiomers of such compounds are limited [86][87][88]. BMAA was originally isolated from an ethanolic extract of cycad seeds, and an optical analysis of the compound determined the presence of the L-enantiomer [89,90].…”

“…BMAA has been analytically detected in cyanobacteria [87,100] and is considered to also be produced by diatoms and possibly dinoflagellates [101][102][103][104][105][106], although little research has been performed on the enantiomers that are present in these organisms. Previous methods have separated synthetic L-and D-BMAA standards using derivatized [86,88] and underivatized [87] methods. The presence of BMAA enantiomers has been investigated in cycads [87,88], cyanobacteria and in mammalian liver, blood and CNS after dosing with synthetic L-BMAA [87].…”

“…Previous methods have separated synthetic L-and D-BMAA standards using derivatized [86,88] and underivatized [87] methods. The presence of BMAA enantiomers has been investigated in cycads [87,88], cyanobacteria and in mammalian liver, blood and CNS after dosing with synthetic L-BMAA [87]. Although the presence of D-BMAA has not so far been widely reported, this enantiomer has been shown to be neurotoxic and was found in the central nervous system of mammals after dosing with L-BMAA [87,107].…”

Perspectives on Endosymbiosis in Coralloid Roots: Association of Cycads and Cyanobacteria

“…The neurotoxins cause an amyotrophic lateral sclerosis/parkinsonism-dementia complex (ALS-PDC) (Brownson et al, 2002; Meneely et al, 2016). ALS-PDC is a progressive neurodegenerative disease that infected high number of Chamorro people in Guam (Metcalf et al, 2017; Zurita et al, 2019). The disease was believed to be transmitted by flying foxes that consumed cycad seeds.…”

“…This neurotoxin was claimed to be β-methylamino-L-alanine (BMAA), a non-proteinogenic amino acid produced by cyanobacteria. Even though some studies have showed that cycad host plants contain BMAA (Vega and Bell, 1967; Polsky et al, 1972; Brownson et al, 2002; Banack and Cox, 2003; Cox et al, 2003), an accurate detection method of BMAA is still being perfected until the present (Metcalf et al, 2017; Zurita et al, 2019) due to various structural isomers (Rosén and Hellenäs, 2008; Banack et al, 2010; Jiang et al, 2012) making it difficult to correctly identify the compound as BMAA. And thus, all previous claims that BMAA was detected still needed further validation.…”