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Improved detection of beta-N-methylamino-L-alanine using N-hydroxysuccinimide ester of N-butylnicotinic acid for the localization of BMAA in blue mussels (Mytilus edulis)
Stockholm University, Faculty of Science, Department of Environmental Science and Analytical Chemistry. Charles University Prague, Czech Republic .
Stockholm University, Faculty of Science, Department of Environmental Science and Analytical Chemistry.
Stockholm University, Faculty of Science, Department of Environmental Science and Analytical Chemistry.
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2015 (English)In: Analytical and Bioanalytical Chemistry, ISSN 1618-2642, E-ISSN 1618-2650, Vol. 407, no 13, p. 3743-3750Article in journal (Refereed) Published
Abstract [en]

beta-N-Methylamino-l-alanine (BMAA) is an important non-protein amino acid linked to neurodegenerative diseases, specifically amyotrophic lateral sclerosis (ALS). Because it can be transferred and bioaccumulated higher up the food chain, it poses significant public health concerns; thus, improved detection methods are of prime importance for the identification and management of these toxins. Here, we report the successful use of N-hydroxysuccinimide ester of N-butylnicotinic acid (C-4-NA-NHS) for the efficient separation of BMAA from its isomers and higher sensitivity in detecting BMAA compared to the current method of choice using 6-aminoquinolyl-N-hydroxysuccinimidyl carbamate (AQC) derivatization. Implementation of this efficient method allowed localization of BMAA in the non-visceral tissues of blue mussels, suggesting that more efficient depuration may be required to remove this toxin prior to consumption. This is a crucial method in establishing the absence or presence of the neurotoxic amino acid BMAA in food, environmental or biomedical samples.

Place, publisher, year, edition, pages
2015. Vol. 407, no 13, p. 3743-3750
Keywords [en]
BMAA, Isomers, Neurotoxin, LC-MS/MS, Improved derivatization, Quaternary ammonium
National Category
Biochemistry and Molecular Biology Analytical Chemistry
Research subject
Analytical Chemistry
Identifiers
URN: urn:nbn:se:su:diva-117428DOI: 10.1007/s00216-015-8597-2ISI: 000353230400019PubMedID: 25821115OAI: oai:DiVA.org:su-117428DiVA, id: diva2:813474
Note

AuthorCount:6;

Available from: 2015-05-22 Created: 2015-05-19 Last updated: 2019-01-11Bibliographically approved
In thesis
1. Amino acids with relevance to health, climate and the environment: Development of mass spectrometric methods
Open this publication in new window or tab >>Amino acids with relevance to health, climate and the environment: Development of mass spectrometric methods
2018 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Amino acids play vital roles in health, either in their native form or chemically modified. Some studies have linked certain non-proteinogenic amino acids to neurodegenerative diseases, such as in the case of β-methylaminoalanine (BMAA). Various environmental pollutants, including carcinogenic polycyclic aromatic compounds, are able to react forming adducts with blood proteins. Amino acids may also be essential in chemical ecology as constituents of flower nectar, potentially used by common feeders as butterflies to synthesize pheromones. Additionally, proteinaceous materials have been detected in aerosols with an apparent potential to influence climate, possibly having a role in cloud formation.

The determination of amino acids presents many challenges, due to the fact that they are most often constituents of complex sample matrices that contain a high level of chemical interferences. In this respect, mass spectrometry (MS) is a selective and sensitive analytical tool that can be used to measure amino acids in biological samples.

In this work, several analytical methods based on MS were developed. (i) First, derivatization with a permanently charged N-hydroxysuccinimide ester of N-butylnicotinic acid (C4-NA-NHS) was used to increase the sensitivity and selectivity for amino acids. This strategy was applied to localize BMAA in both visceral and non-visceral parts of blue mussels. (ii) Moreover, a method was developed to separate and determine L- and D- BMAA in cycad seeds by derivatization with a chiral reagent, (+)-1-(9-fluorenyl) ethyl chloroformate (FLEC). Together with L-BMAA, appreciable amounts of D-BMAA (50.13 ± 0.05 and 4.08 ± 0.04 µg BMAA/g Cycas micronesica, wet weight, respectively) were detected for the first time after enzymatic digestion, suggesting D-BMAA may be bound to proteins or may be a conjugate and released only after hydrolysis. (iii) Derivatization with C4-NA-NHS was applied as well for the determination of amino acids in nectar of Bunias orientalis. The presence of tryptophan and phenylalanine, purportedly used to synthesize anti-aphrodisiac pheromones by nectar feeders (adult male butterflies), could then be observed. (iv) Furthermore, the profiling of amino acids in Arctic aerosols was carried out and was used to measure the contribution of free and polyamino acids in aerosol formation. Levels detected were in the range of 0.02-2914 pmol/m3 sampled air. For the first time the measurement of polyamino acids in the Arctic atmosphere was reported. Additionally, possible anthropogenic and marine sources were suggested. The results support the hypothesis that proteinaceous materials act as cloud condensation nuclei over the Arctic. (v) Finally, a method was developed employing selective chromatography/high-resolution MS to identify histidine and lysine adducts in serum albumin of mice exposed to the carcinogen benzo(a)pyrene, as well as in human samples in vivo. Adduct isomers from diol epoxide metabolites could be detected in serum albumin from human samples at attomole/mg levels. This work shows the possibility of future exposure measurements from these compounds in different groups of the population.

This thesis presents the development of improved analytical methodologies for detecting and identifying trace levels of amino acids, to investigate their relevance in health, climate and the environment.

Place, publisher, year, edition, pages
Stockholm: Department of Environmental Science and Analytical Chemistry, Stockholm University, 2018. p. 53
Keywords
amino acids, LC/MS, fixed-charge derivatization, BMAA, chiral separation, pheromones, arctic aerosols, serum albumin adducts, benzo[a]pyrene diol epoxides, high-resolution MS
National Category
Analytical Chemistry
Research subject
Analytical Chemistry
Identifiers
urn:nbn:se:su:diva-158985 (URN)978-91-7797-390-4 (ISBN)978-91-7797-391-1 (ISBN)
Public defence
2018-12-05, Nordenskiöldsalen, Geovetenskapens hus, Svante Arrhenius väg 12, Stockholm, 13:00 (English)
Opponent
Supervisors
Note

At the time of the doctoral defense, the following papers were unpublished and had a status as follows: Paper 2: Manuscript. Paper 3: Manuscript. Paper 5: Manuscript.

Available from: 2018-11-12 Created: 2018-08-20 Last updated: 2018-11-12Bibliographically approved
2. Mass-spectrometry based survey of BMAA sources, distribution and transfer
Open this publication in new window or tab >>Mass-spectrometry based survey of BMAA sources, distribution and transfer
2019 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

β-methylaminoalanine (BMAA) is a neurotoxic non-protein amino acid first isolated from cycad seeds in 1967. It is believed to be connected to neurodegenerative diseases such as Parkinson’s, Alzheimer’s and amyotrophic lateral sclerosis (ALS) and is a ubiquitous compound produced by cyanobacteria, diatoms and dinoflagellates. Consequently, elucidating natural production, distribution and routes for human exposure of BMAA are of particular importance. However, the natural function of BMAA and its mechanisms of toxicity have not been fully established yet. The contradictory results about BMAA presence in cyanobacterial cultures and food webs have been reported by different scientific groups, which required the development of more sensitive and reliable analytical methods. 

This thesis is focused on the analytical chemistry dimension of BMAA research: covering both new method development and novel applications. New analytical methods for BMAA detection and quantification were developed, focusing on improving sensitivity, since BMAA is normally found in natural samples at low concentrations. In Paper I, a new derivatization technique was implemented, which increased sensitivity and selectivity in the analysis of BMAA and its isomers. Subsequently, this developed method was applied to determine the presence of BMAA in fat and oil matrices in Paper II, which is a step towards discovering BMAA forms other than the documented free and protein-bound BMAA species. In Paper III, a method for separation and quantification of L- and D-BMAA stereoisomers in complex biological matrix was developed and applied to determine the enantiomeric composition of BMAA in cycad seed. Studying environmental distribution of BMAA is important to evaluate potential exposure routes and health risks for humans. Part of the work was devoted to broaden assessment on environmental occurrence of BMAA by applying existing robust methodology to new samples, such as commercial seafood in Paper IV and Baltic Sea biota in Paper V. Some of the “overlooked” aspects in the existing BMAA literature (i.e., BMAA chiral analysis, possible BMAA presence in dietary oil supplements and defined food webs) were successfully addressed. 

Overall, the thesis presents important analytical developments, which can help to further elucidate sources, distribution and transfer of BMAA.

Place, publisher, year, edition, pages
Stockholm: Department of Environmental Science and Analytical Chemistry, Stockholm University, 2019. p. 60
Keywords
BMAA, LC-MS/MS, chiral analysis, seafood, toxins, Baltic Sea, derivatization
National Category
Analytical Chemistry
Research subject
Analytical Chemistry
Identifiers
urn:nbn:se:su:diva-164088 (URN)978-91-7797-544-1 (ISBN)978-91-7797-545-8 (ISBN)
Public defence
2019-02-28, Nordenskiöldsalen, Geovetenskapens hus, Svante Arrhenius väg 12, Stockholm, 10:00 (English)
Opponent
Supervisors
Note

At the time of the doctoral defense, the following papers were unpublished and had a status as follows: Paper 2: Manuscript. Paper 5: Manuscript.

Available from: 2019-02-05 Created: 2019-01-11 Last updated: 2019-01-22Bibliographically approved

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