CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf
Mass-spectrometry based survey of BMAA sources, distribution and transfer
Stockholm University, Faculty of Science, Department of Environmental Science and Analytical Chemistry.ORCID iD: 0000-0002-6946-6832
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 [en]
BMAA, LC-MS/MS, chiral analysis, seafood, toxins, Baltic Sea, derivatization
National Category
Analytical Chemistry
Research subject
Analytical Chemistry
Identifiers
URN: urn:nbn:se:su:diva-164088ISBN: 978-91-7797-544-1 (print)ISBN: 978-91-7797-545-8 (electronic)OAI: oai:DiVA.org:su-164088DiVA, id: diva2:1278106
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
List of papers
1. 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)
Open this publication in new window or tab >>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)
Show others...
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.

Keywords
BMAA, Isomers, Neurotoxin, LC-MS/MS, Improved derivatization, Quaternary ammonium
National Category
Biochemistry and Molecular Biology Analytical Chemistry
Research subject
Analytical Chemistry
Identifiers
urn:nbn:se:su:diva-117428 (URN)10.1007/s00216-015-8597-2 (DOI)000353230400019 ()25821115 (PubMedID)
Note

AuthorCount:6;

Available from: 2015-05-22 Created: 2015-05-19 Last updated: 2019-01-11Bibliographically approved
2. Analysis of BMAA in fish oil and its vegan alternatives
Open this publication in new window or tab >>Analysis of BMAA in fish oil and its vegan alternatives
(English)Manuscript (preprint) (Other academic)
National Category
Analytical Chemistry
Research subject
Analytical Chemistry
Identifiers
urn:nbn:se:su:diva-164084 (URN)
Available from: 2019-01-11 Created: 2019-01-11 Last updated: 2019-01-15Bibliographically approved
3. Chiral separation of beta-Methylamino-alanine (BMAA) enantiomers after (+)-1-(9-fluorenyl)-ethyl chloroformate (FLEC) derivatization and LC-MS/MS
Open this publication in new window or tab >>Chiral separation of beta-Methylamino-alanine (BMAA) enantiomers after (+)-1-(9-fluorenyl)-ethyl chloroformate (FLEC) derivatization and LC-MS/MS
Show others...
2019 (English)In: Analytical Methods, ISSN 1759-9660, E-ISSN 1759-9679, Vol. 11, p. 432-442Article in journal (Refereed) Published
Abstract [en]

β-Methylamino-L-alanine, a neurotoxin first isolated from the seeds of cycad tree Cycas circinalis, is widely spread in a variety of environments. New sensitive techniques and robust methodologies are needed to detect its presence in complex biological samples and to further understand its biochemical properties. In this context, the determination of the enantiomeric composition of natural BMAA is of great importance. In this study, a simple and easily implemented LC-ESI-MS/MS method was developed to determine the presence of both D- and L-BMAA enantiomers in samples of cycad seed (Cycas micronesica). The samples were subjected to enzymatic hydrolysis to avoid racemization that occurs during strong acid hydrolysis. Derivatization with (+)-1-(9-fluorenyl)-ethyl chloroformate (FLEC) was performed prior to LC-ESI-MS/MS to produce chromatographically separable derivatives of D- and L-BMAA. Together with the retention time, two MRM transitions and their peak area ratios were used to identify the compounds. The LOQ obtained was 0.3 μg BMAA per g wet weight for each enantiomer. Method repeatability was within 3 RSD% both intraday and interday and accuracy was 98–108%. An accurate enantiomeric composition was obtained from the samples of cycad seed, where L- and D-BMAA were detected at 50.13 ± 0.05 and 4.08 ± 0.04 μg BMAA per g wet weight respectively (n = 3).

National Category
Analytical Chemistry
Research subject
Analytical Chemistry
Identifiers
urn:nbn:se:su:diva-164087 (URN)10.1039/C8AY02287A (DOI)000457360700016 ()
Available from: 2019-01-11 Created: 2019-01-11 Last updated: 2019-03-04Bibliographically approved
4. Quantification of neurotoxin BMAA (beta-N-methylamino-L-alanine) in seafood from Swedish markets
Open this publication in new window or tab >>Quantification of neurotoxin BMAA (beta-N-methylamino-L-alanine) in seafood from Swedish markets
2014 (English)In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 4, article id 6931Article in journal (Refereed) Published
Abstract [en]

The neurotoxin beta-N-methylamino-L-alanine (BMAA) produced naturally by cyanobacteria, diatoms and dinoflagellates can be transferred and accumulated up the food chain, and may be a risk factor for neurodegenerative diseases. This study provides the first systematic screening of BMAA exposure of a large population through the consumption of seafood sold in metropolitan markets. BMAA was distinguished from known isomers by liquid chromatography tandem mass spectrometry after acidic hydrolysis and derivatization. Using deuterium-labeled internal standard, BMAA was quantified as 0.01-0.90 mu g/g wet weight of tissues in blue mussel, oyster, shrimp, plaice, char and herring, but was undetectable (<0.01 mu g/g) in other samples (salmon, cod, perch and crayfish). Provided that the content of BMAA detected is relevant for intake calculations, the data presented may be used for a first estimation of BMAA exposure through seafood from Swedish markets, and to refine the design of future toxicological experiments and assessments.

National Category
Analytical Chemistry
Research subject
Analytical Chemistry
Identifiers
urn:nbn:se:su:diva-110174 (URN)10.1038/srep06931 (DOI)000344315200003 ()
Note

AuthorCount:4;

Available from: 2015-02-09 Created: 2014-12-08 Last updated: 2019-01-15Bibliographically approved
5. Is there BMAA transfer in the pelagic and benthic food webs in the Baltic Sea?
Open this publication in new window or tab >>Is there BMAA transfer in the pelagic and benthic food webs in the Baltic Sea?
Show others...
(English)Manuscript (preprint) (Other academic)
National Category
Analytical Chemistry
Research subject
Analytical Chemistry
Identifiers
urn:nbn:se:su:diva-164086 (URN)
Available from: 2019-01-11 Created: 2019-01-11 Last updated: 2019-01-15Bibliographically approved

Open Access in DiVA

Mass-spectrometry based survey of BMAA sources, distribution and transfer(1940 kB)121 downloads
File information
File name FULLTEXT01.pdfFile size 1940 kBChecksum SHA-512
b3fa6e600f98ac5486f43e14a46c19ac362bc012e7627a21ff98d48fbd2d341c4c00a039e58f05b04f501853fa85a561e080b57a2d0573ad2cb23e5e0dcd3650
Type fulltextMimetype application/pdf

Search in DiVA

By author/editor
Zguna, Nadezda
By organisation
Department of Environmental Science and Analytical Chemistry
Analytical Chemistry

Search outside of DiVA

GoogleGoogle Scholar
Total: 121 downloads
The number of downloads is the sum of all downloads of full texts. It may include eg previous versions that are now no longer available

isbn
urn-nbn

Altmetric score

isbn
urn-nbn
Total: 350 hits
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf