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Arsenolipids



A wide range of organic compounds that contain atoms of arsenic have been found in marine organisms, and these include lipids, although they are usually present at low levels. Some authors take a rather wide view of what constitutes an arsenolipid and thus define compounds such as trimethylarsine and its metabolites as lipids, simply on the basis of their solubility in organic solvents. Here, only those lipids that have been characterized sufficiently to be certain that they contain long aliphatic chains and arsenic atoms somewhere in the molecule are considered.


1.  Hydrocarbons and Fatty Acids containing Arsenic Atoms

Long-chain hydrocarbons with a terminal dimethylarsinoyl moiety were first isolated and characterized from capelin, Mallotus villosus, as recently as 2008, and they have since been detected in other fish species and in brown algae. The main isomer is 1-dimethylarsinoylpentadecane, found together with C17 and C19 analogues as well as one thought to be 1-dimethylarsinoyl all-cis-4,7,10,13,16,19-docosahexaene, if a biosynthetic relationship to docosahexaenoic acid is assumed. In one organism, traces of even-numbered species were found, and further species with one to five double bonds have now been identified. Indeed, an arsenohydrocarbon with seven double bonds has been detected in oils from cod and blue whiting (C35H56AsO).

Formula of 1-dimethylarsinoylpentadecane

Similarly, a series of saturated fatty acids with a terminal dimethylarsinoyl moiety and with 15 to 19 carbon atoms was detected initially in cod-liver oil, i.e. the dimethylarsinoyl group appears to replace the terminal methyl group of conventional even-numbered fatty acids. In addition, unsaturated fatty acids, which are related structurally to oleic, docosapentaenoic and docosahexaenoic fatty acids, were detected, although only one fatty acid with an even-number of carbon atoms was found, i.e. C24H38AsO3. However, an even wider range of such fatty acids has been detected in further studies, and more will no doubt be reported in future. The two fatty acids illustrated below are presumably related biosynthetically to hexadecanoic and docosapentaenoic acids. All fish oils examined appear to contain a similar range of hydrocarbons and fatty acids of this type, with the proportions varying somewhat among species and at overall concentrations of 4.3 to 10.5 mg per kg.

Formulae of arseno-fatty acids

In some species, arsinoyl fatty acids were not found to be linked to the complex lipids, but in herring roe, mass spectrometry established that highly unsaturated fatty acids of this type were esterified in phosphatidylcholine, while in salmon roe, an analogous C30 fatty acid with eight double bonds was detected in the phosphatidylethanolamine fraction. In addition, evidence has been obtained for their presence in triacylglycerols from blue whiting.

The mechanism for the biosynthesis of these compounds is a matter for speculation at present, and it has been suggested that dimethylarsinoylpropionic acid might be the primer molecule for a fatty acid synthase, for example. Similarly, it is only possible to speculate where these compounds arise in the marine food-chain, but brown algae are one potential source.

One further type of arsenolipid with a long alkyl chain to have been discovered consists of cationic trimethylarsenio fatty alcohols of which two molecular species have so far been detected in fish oils.

A cationic trimethylarsenio fatty alcohol


2.  Glycerolipids containing Arsenic Atoms in the Polar Head Group

The presence of a number of arsenic-containing complex lipids has been inferred from degradative studies of marine lipids in which arsenical compounds have been isolated from hydrolysates. These include analogues of phosphatidylcholine and sphingomyelin, but they are present at such low levels that it has not been possible to isolate them in pure form for definitive characterization. For example, based simply on the isolation and identification of glycerophosphorylarsenocholine after alkaline hydrolysis of lipid extracts, it appears certain that phosphatidylarsenocholine is a minor component of the lipids of mullet, lobster and other marine species.

Formula of phosphatidylarsenocholine

Similarly, it has been known for some time from studies of lipid hydrolysates that a complex arsenic-containing glycophospholipid is present in fish and other marine organisms, i.e. diacylglycerophospho-2-hydroxypropyl-5-deoxy-5-(dimethylarsinoyl)-β-ribofuranoside, and this has now been characterized definitively from several species of multicellular brown algae (seaweeds) by modern mass spectrometric methods.

Formula of arsenic-containing glycophospholipid

In the brown alga Saccharina latissima, the main fatty acids in this lipid are saturated (C15 to C20) with 16:0 predominating, although small amounts of unsaturated fatty acids are also present (16:1 to 18:3); much of the palmitic acid is in position sn-2 of the glycerol moiety. The more conventional phospholipids in the organism had very different fatty acid compositions. The fresh water cyanobacterium Synechocystis sp. PCC 6803 also contains this lipid, and it requires exogenous trimethylarsine for biosynthesis of the presumed arsenosugar precursor. In contrast, Nostoc sp. PCC 7120, a typical filamentous cyanobacterium ubiquitous in aquatic systems, is able both to methylate inorganic arsenic and to produce arsenosugars and thence the arsenosugar phospholipid with C17 saturated and unsaturated fatty acid components; it does not produce arsenohydrocarbons. A mono-acyl (lyso) form of the lipid has been found in the brown alga Saccharina japonica.


3.  Toxicity

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. When arsenolipids are absorbed from the gastrointestinal tract of mice and humans, much of the arsenic was believed to be excreted rapidly in the form of organic water-soluble metabolites, mainly compounds containing dimethylarsine oxide moieties and arsenobetaine. However, arsenic-containing hydrocarbons were recently reported to be highly toxic in tests with cultured cells from human bladder and liver and in studies with Drosophila melanogaster. Further, although arsenic-containing fatty acids were less toxic in comparison to arsenic-containing hydrocarbons and arsenite, significant effects were observable at µM concentrations in human liver cells. In experiments with a model intestinal barrier system, both lipid classes were reportedly able to diffuse passively into the intestinal cells, although the arsenic-containing fatty acids were largely metabolized before crossing into the blood stream. However, arsenic-containing hydrocarbons and fatty acids have both been detected in human milk albeit at very low levels.


4.  Analysis

The main difficulty in the analysis of arsenolipids is the low levels at which they occur naturally. The dimethylarsinoyl group imparts considerable additional polarity to arsenolipids, but a new procedure in which the extracts are reacted with hydrogen sulfide to convert oxo-arsenolipids to thio compounds permits sharper peaks on chromatography with improvements in resolution and quantification by mass spectrometry.


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Lipid listings Credits/disclaimer Updated: October 7th, 2017 Author: William W. Christie LipidWeb icon