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Amino acids with relevance to health, climate and the environment: Development of mass spectrometric methods
Stockholm University, Faculty of Science, Department of Environmental Science and Analytical Chemistry.ORCID iD: 0000-0003-2561-6875
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 [en]
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: urn:nbn:se:su:diva-158985ISBN: 978-91-7797-390-4 (print)ISBN: 978-91-7797-391-1 (electronic)OAI: oai:DiVA.org:su-158985DiVA, id: diva2:1240260
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
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)
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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.

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: 2018-08-22Bibliographically approved
2. LC-MS/MS for chiral separation of β-Methylamino-L-alanine (BMAA) enantiomers after (+)-1-(9-fluorenyl)-ethyl chloroformate (FLEC) derivatization
Open this publication in new window or tab >>LC-MS/MS for chiral separation of β-Methylamino-L-alanine (BMAA) enantiomers after (+)-1-(9-fluorenyl)-ethyl chloroformate (FLEC) derivatization
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(English)Manuscript (preprint) (Other academic)
National Category
Analytical Chemistry
Research subject
Analytical Chemistry
Identifiers
urn:nbn:se:su:diva-159094 (URN)
Available from: 2018-08-21 Created: 2018-08-21 Last updated: 2018-08-22Bibliographically approved
3. Anti-aphrodisiac pheromone, a renewable signal in adult butterflies
Open this publication in new window or tab >>Anti-aphrodisiac pheromone, a renewable signal in adult butterflies
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(English)Manuscript (preprint) (Other academic)
National Category
Analytical Chemistry
Research subject
Analytical Chemistry
Identifiers
urn:nbn:se:su:diva-159095 (URN)
Available from: 2018-08-21 Created: 2018-08-21 Last updated: 2018-08-22Bibliographically approved
4. Measurements of Atmospheric Proteinaceous Aerosol in the Arctic Using a Selective UHPLC/ESI-MS/MS Strategy
Open this publication in new window or tab >>Measurements of Atmospheric Proteinaceous Aerosol in the Arctic Using a Selective UHPLC/ESI-MS/MS Strategy
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2018 (English)In: Journal of the American Society for Mass Spectrometry, ISSN 1044-0305, E-ISSN 1879-1123Article in journal (Refereed) Epub ahead of print
Abstract [en]

In this article, an analytical methodology to investigate the proteinaceous content in atmospheric size-resolved aerosols collected at the Zeppelin observatory (79 °N, 12 °E) at Ny Ålesund, Svalbard, from September to December 2015, is proposed. Quantitative determination was performed after acidic hydrolysis using ultrahigh-performance liquid chromatography in reversed-phase mode coupled to electrospray ionization tandem mass spectrometry. Chromatographic separation, as well as specificity in the identification, was achieved by derivatization of the amino acids with N-butyl nicotinic acid N-hydroxysuccinimide ester prior to the analysis. The chromatographic run was performed within 11 min and instrumental levels of detection (LODs) were between 0.2 and 8.1 pg injected on the column, except for arginine which exhibited an LOD of 37 pg. Corresponding method LODs were between 0.01 and 1.9 fmol/m3, based on the average air sampling volume of 57 m3. The sum of free amino acids and hydrolyzed polyamino acids was shown to vary within 6–2914 and 0.02–1417 pmol/m3 for particles in sizes < 2 and 2–10 μm in equivalent aerodynamic diameter, respectively. Leucine, alanine, and valine were the most abundant among the amino acids in both aerosol size fractions. In an attempt to elucidate source areas of the collected aerosols, 5- to 10-day 3D backward trajectories reaching the sampling station were calculated. Overall, the method described here provides a first time estimate of the proteinaceous content, that is, the sum of free and polyamino acids, in size-resolved aerosols collected in the Arctic.

Keywords
Proteins, Amino acids, Arctic aerosols, LC/MS, Fixed-charge derivatization
National Category
Analytical Chemistry Meteorology and Atmospheric Sciences
Research subject
Analytical Chemistry
Identifiers
urn:nbn:se:su:diva-155614 (URN)10.1007/s13361-018-2009-8 (DOI)
Available from: 2018-04-25 Created: 2018-04-25 Last updated: 2018-11-27
5. Detection of benzo[a]pyrene diol epoxide adducts to histidine and lysine in serum albumin in vivo by high-resolution-tandem mass spectrometry
Open this publication in new window or tab >>Detection of benzo[a]pyrene diol epoxide adducts to histidine and lysine in serum albumin in vivo by high-resolution-tandem mass spectrometry
Show others...
(English)Manuscript (preprint) (Other academic)
National Category
Analytical Chemistry
Research subject
Analytical Chemistry
Identifiers
urn:nbn:se:su:diva-159093 (URN)
Available from: 2018-08-21 Created: 2018-08-21 Last updated: 2018-08-22Bibliographically approved

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