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Arsenic-Containing Phosphatidylcholines Discovered in Herring Caviar

(16.04.2016)


Background:
Arsenic-containing lipids, so-called arsenolipids, are natural constituents of marine organisms already observed in the late 70s. The first arsenolipid to be rigorously identified was an arsenosugar lipid which was isolated from a brown alga. Since this lipid was related to the major water-soluble arsenic compounds found in marine algae, it seemed plausible to understand  its biosynthesis as part of an arsenic detoxification process.


structures of an arsenic-containing fatty acid (C15-FA) and an As-containing hydrocarbon (C15-HC)











Figure 1: Examples of an arsenic-containing fatty acid (C15-FA)
and an As-containing hydrocarbon (C15-HC)


However, more recent research has revealed several new groups of naturally occurring arsenolipids, including arsenic-containing fatty acids (AsFA) and hydrocarbons (AsHC; Figure 1), which clearly have a biosynthetic origin different from that of the arsenosugar lipids.

Also, an initial conclusion that the presence of most of these lipids in fish oils does not appear to raise toxicity problems when they are consumed by mammals may now have to be challenged.

The new study:
In a recent study of a fish oil, researchers had observed the presence of an unidentified group of arsenolipids.  Because they could be base-hydrolysed to known arsenic fatty acids, they were thought to be conjugates of arsenic fatty acids. Unfortunately the low concentration of these compounds in fish oil hindered their identification by ESI-MS. Since the researchers came up with the idea that this group of arsenolipids might be related to phosphatidyl compounds integral to membrane chemistry, they investigated fish eggs as a richer source of cell membrane compounds.

Freeze-dried herring caviar originating from the Norwegian Sea was extracted with dichloromethane/methanol. Washing the extract with water yielded an organic layer containing approximately 80% of the initial arsenic of about 0.8 µg/g dry mass. After removal of the solvent, the residue was re-dissolved in absolute ethanol and analysed by reversed-phase HPLC coupled to an elemental mass spectrometer (inductively coupled plasma mass spectrometry, ICP-MS). Arsenic speciation analysis by HPLC-ICP-MS  revealed the presence of several known arsenic fatty acids and arsenic hydrocarbons, in addition to a cluster of later-eluting arsenolipids.

In order to identify these species, further mass spectrometric analyses were performed by using HPLC coupled via an electrospray ionization source (operated in positive mode) to a high-accuracy mass spectrometer with collision induced-dissociation capability. During the elution, a large number (approximately 700) of distinct ions were isolated and fragmented, yielding more than 18 000 MS/MS spectra in each run. Searching the fragmentation spectra for the fragments of dimethylarsinoyl group resulted in a multitude of precursor ions, from which six already known arsenic fatty acids and five known arsenic hydrocarbons could be identified. In the later part of the HPLC-ESI-MS chromatogram five arsenic containing phosphatidylcholines were identified (one example shown in figure 2).


Figure 2: Proposed structures for one of the five AsPCs found in herring caviar.


Phosphatidylcholines form a major lipid class comprising many compounds varying only in their fatty acid composition. The researchers therefore believe that the cluster of unresolved arsenic compounds observed late within the HPLC-ICP-MS chromatograms, which collectively constitute roughly 50% of the total arsenic, belong predominantly to the new group of arsenic phosphatidylcholines. This study identified five of those compounds, and opens the door to discovering many more of these complex arsenic natural products.



The cited study:

Sandra A. Viczek, Kenneth B. Jensen, Kevin A. Francesconi, Arsenic-Containing Phosphatidylcholines: A New Group of Arsenolipids Discovered in Herring Caviar, Angew. Chem., 128/17 (2016) 5345–5348. DOI: 10.1002/ange.201512031



Related studies (newest first):

S. Meyer, G. Raber, F. Ebert, L. Leffers, S.M. Müller, M.S. Taleshi, K.A. Francesconi, T. Schwerdtle, In vitro toxicological characterisation of arsenic-containing fatty acids and three of their metabolites, Toxicol. Res., 4 (2015) 1289-1296. DOI: 10.1039/c5tx00122f

Mojtaba S. Taleshi, Georg Raber, John S. Edmonds, Kenneth B. Jensen, Kevin A. Francesconi, Arsenolipids in oil from blue whiting Micromesistius poutassou – evidence for arsenic-containing esters, Sci. Rep., 4 (2015) 7492. DOI: 10.1038/srep07492

Mojtaba S. Taleshi, Rune K. Seidler-Egdal, Kenneth B. Jensen, Tanja Schwerdtle, Kevin A. Francesconi, Synthesis and Characterization of Arsenolipids: Naturally Occurring Arsenic Compounds in Fish and Algae, Organometallics, 33 (2014) 1397-1403. DOI: 10.1021/om4011092

S. Meyer, M. Matissek, S.M. Müller, M.S. Taleshi, F. Ebert, K.A. Francesconi, T. Schwerdtle, In vitro toxicological characterisation of three arsenic-containing hydrocarbons, Metallomics, 6 (2014) 1023-1033. DOI: 10.1039/c4mt00061g

Kenneth O. Amayo, Andrea Raab, Eva M. Krupp, Talke Marschall, Michael Horsfall, Jorg Feldmann, Arsenolipids show different profiles in muscle tissues of four commercial fish species, J. Trace Elem. Med. Biology, 28 (2014) 131–137. DOI: 10.1016/j.jtemb.2013.11.004 

Ronald A. Glabonjat, Georg Raber, Kenneth B. Jensen, Josef Ehgartner, Kevin A. Francesconi, Quantification of Arsenolipids in the Certified Reference Material NMIJ 7405.a (Hijiki) using HPLC/Mass Spectrometry after Chemical Derivatization, Anal. Chem., 86 (2014) 10282-10287. DOI: 10.1021/ac502488f

Veronika Sele, Jens J. Sloth, Bjarte Holmelid, Stig Valdersnes, Kasper Skov, Heidi Amlund, Arsenic-containing fatty acids and hydrocarbons in marine oils – determination using reversed-phase HPLC–ICP-MS and HPLC–qTOF-MS, Talanta, 121(2014) 89–96. DOI: 10.1016/j.talanta.2013.12.049

S. Lischka, U. Arroyo-Abad, J. Mattusch, A. Kühn, Ch. Piechotta, The high diversity of arsenolipids in herring fillet (Clupea harengus), Talanta, 110 (2013) 144-152. doi: 10.1016/j.talanta.2013.02.051

Uriel Arroyo-Abad, Susanne Lischka, Christian Piechotta, Jürgen Mattusch, Thorsten Reemtsma, Determination and identification of hydrophilic and hydrophobic arsenic species in methanol extract of fresh cod liver by RP-HPLC with simultaneous ICP-MS and ESI-Q-TOF-MS detection, Food Chem., 141/3 (2013) 3093-3102. doi: 10.1016/j.foodchem.2013.05.152

Veronika Sele, Heidi Amlund, Marc H.G. Berntssen, Jannicke A. Berntsen, Kasper Skov, Jens J. Sloth, Detection of arsenic-containing hydrocarbons in a range of commercial fish oils by GC-ICPMS analysis, Anal. Bioanal. Chem., 405 (2013) 5179–5190. DOI: 10.1007/s00216-013-6925-y

Kenneth O. Amayo, Andrea Raab, Eva M. Krupp, Helga Gunnlaugsdottir, Jörg Feldmann, Novel Identification of Arsenolipids Using Chemical Derivatizations in Conjunction with RP-HPLC-ICPMS/ESMS, Anal. Chem., 85 (2013) 9321-9327. DOI: 10.1021/ac4020935

Andrea Raab, Chris Newcombe, Dominik Pitton, Rainer Ebel, Jörg Feldmann, Comprehensive Analysis of Lipophilic Arsenic Species in a Brown Alga (Saccharina latissima), Anal. Chem., 85 (2013) 2817-2824. DOI: 10.1021/ac303340t  

Sara García-Salgado, Georg Raber, Reingard Raml, Christoph Magnes, Kevin A. Francesconi, Arsenosugar phospholipids and arsenic hydrocarbons in two species of brown macroalgae, Environ. Chem., 9 (2012) 63–66. DOI: 10.1071/EN11164 

Maria Jose Ruiz-Chancho, Mojtaba S. Taleshi, Walter Goessler, Kevin A. Francesconi, A method for screening arsenolipids in fish oils by HPLC-ICPMS, J. Anal. At. Spectrom., 27 (2012) 501-504. DOI: 10.1039/c1ja10260e

Veronika Sele, Jens J. Sloth, Anne-Katrine Lundebye, Erik H. Larsen, Marc H.G. Berntssen, Heidi Amlund, Arsenolipids in marine oils and fats: A review of occurrence, chemistry and future research needs, Food Chem. , 133 (2012) 618–630. doi: 10.1016/j.foodchem.2012.02.004

Kenneth O. Amayo, Asta Petursdottir, Chris Newcombe, Helga Gunnlaugsdottir, Andrea Raab, Eva M. Krupp, Jörg Feldmann, Identification and Quantification of Arsenolipids Using Reversed-Phase HPLC Coupled Simultaneously to High-Resolution ICPMS and High-Resolution Electrospray MS without Species-Specific Standards, Anal. Chem., 83 (2011) 3589–3595. doi: 10.1021/ac2005873

Uriel Arroyo-Abada, Jürgen Mattusch, Sibylle Mothes, Monika Moder, Rainer Wennrich, Maria P. Elizalde-Gonzalez, Frank-Michael Matysik, Detection of arsenic-containing hydrocarbons in canned cod liver tissue, Talanta, 82 (2010) 38–43. doi: 10.1016/j.talanta.2010.03.054

M.S. Taleshi, J.S. Edmonds,  W. Goessler, G. Raber, Kenneth B. Jensen, K.A. Francesconi, Arsenic-Containing Lipids Are Natural Constituents of Sashimi Tuna, Environ. Sci. Technol., 44 (2010) 1478–1483. doi: 10.1021/es9030358

Georg Raber, Reingard Raml, Walter Goessler and Kevin A. Francesconi, Quantitative speciation of arsenic compounds when using organic solvent gradients in HPLC-ICPMS, J. Anal. At. Spectrom., 25 (2010) 570–576. DOI: 10.1039/b921881e

Alice Rumpler, John S. Edmonds, Mariko Katsu, Kenneth B. Jensen, Walter Goessler, Georg Raber, Helga Gunnlaugsdottir, Kevin A. Francesconi, Arsenic-Containing Long-Chain Fatty Acids in Cod-Liver Oil: A Result of Biosynthetic Infidelity?, Angew. Chem., Int. Ed. Engl., 47/14 (2008) 2665-2667. doi: 10.1002/anie.200705405

Mojtaba S. Taleshi, Kenneth B. Jensen, Georg Raber, John S. Edmonds, Helga Gunnlaugsdottir, Kevin A. Francesconi, Arsenic-containing hydrocarbons: natural compounds in oil from the fish capelin, Mallotus villosus, Chem. Commun., 39 (2008) 4706–4707. DOI: 10.1039/b808049f

Ernst Schmeisser, Walter Goessler, Kevin A. Francesconi, Human metabolism of arsenolipids present in cod liver, Anal. Bioanal. Chem., 385/2 (2006) 367-376. DOI: 10.1007/s00216-006-0401-x

E. Schmeisser, A. Rumpler, M. Kollroser, G. Rechberger, W. Goessler, Kevin A. Francesconi, Arsenic fatty acids are human urinary metabolites of arsenolipids present in cod liver, Angew. Chem., Int. Ed. Engl., 45 (2006) 150-154. doi: 10.1002/anie.200502706

Ernst Schmeisser, Walter Goessler, Norbert Kienzl, Kevin A. Francesconi, Direct measurement of lipid-soluble arsenic species in biological samples with HPLC-ICPMS, Analyst (London), 130/6 (2005) 948-955. doi: 10.1039/b502445e

Valery M. Dembitsky, Dmitrii O. Levitsky, Arsenolipids,  Prog. Lipid Res., 43/5 (2004) 403-448. doi: 10.1016/j.plipres.2004.07.001

Mariko Miyajima, Noriaki Hamada, Etsuro Yoshimura, Akira Okubo, Sunao Yamazaki, Shozo Toda, Lipophilic arsenic compound(s) in the liver of a tiger shark (Galeocerdo cuvier), Appl. Organomet. Chem., 2 (1988) 377-384. doi: 10.1002/aoc.590020416

Masatoshi Morita, Yasuyuki Shibata, Isolation and Identification of Arseno-lipid from a Brown Alga, Undaria Pinnatifida (Wakame), Chemosphere, 17/6 (1988) 1147-1152. DOI: 10.1016/0045-6535(88)90180-4

G. Lunde, Analysis of Arsenic in Marine Oils by Neutron Activation. Evidence of Arseno Organic Compounds, J. Am. Oil Chem. Soc., 45 (1968) 331-332. DOI: 10.1007/BF02667103



Related EVISA Resources

Brief summary: Speciation and Toxicity
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Link database: Human exposure from arsenic in the diet
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Link Page: All about food science
Material Database: Materials for Arsenic speciation analysis



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