Miscellaneous Sulfur-Containing Lipids

1.   Chlorosulfolipids

The phytoflagellate Ochromonas danica (a chrysophyte alga) contains a number of linear alkanes (C22 and C24) substituted with sulfate groups and with both sulfate groups and chlorine, i.e. chlorosulfolipids, the discovery and exploration of which are largely associated with Thomas H. Haines. Generally, there are two sulfate groups in the 1 and 14 positions of the C22 alkyl chain (positions 1 and 15 of the C24 compounds), and there can be one to six chlorine atoms in various positions. They constitute approximately 15% of the total lipids, but 90% of the polar lipids of the flagella. Eight chlorosulfolipids have now been characterized from this organism, and some representative examples are illustrated. The stereochemistry of the of the substituents in the major component, 'danicalipin A' (the last illustrated), has been determined.

Structures of some chlorosulfolipids of Ochromonas danica

Many aspects of the biosynthesis of these unusual lipids remain to be confirmed, but it is believed that docosanoic acid is hydroxylated at C14, before reduction to the 1,14-diol and sulfation. Chlorine atoms are presumed to be inserted into the saturated alkyl chain of the 1,14-diol sulfate in a stepwise fashion by a free radical process involving chlorinases, which have yet to be characterized. The two endpoints of the biosynthetic process are 2,2,11,13,15,16-hexachloro-1,14-docosanediol disulfate and 2,2,12,14,16,17-hexachloro-1,15-tetracosanediol disulfate. O. danica is unable to remove the sulfate groups, so the lipids are remarkably inert metabolically.

Such a high proportion of chlorosulfolipids (and an absence of phospholipids) in the flagella of O. danica implies that they must be the major constituents of the membranes of this organelle, which must be differentiated in some manner from the contiguous exterior surface membranes. At first glance, it is not easy to understand how such lipids, which are highly soluble in water and carry a polar substituent in the centre of the hydrocarbon chain, can form a membrane bilayer. This can only be possible if there are some positively charged ions buried deep in the hydrocarbon layer that shield the negative sulfate groups. Haines has postulated that an as yet unidentified molecule, possibly a divalent metal ion or protein bearing charged residues, offsets the negative charge of the sulfate group at the physiological pH. The anionic lipid head groups may serve as a proton-conducting pathway along the surface of membranes.

Since the initial studies, a range of further chloro- and bromosulfolipids have been found in algae and other organisms, and as toxins affecting shellfish. Many of the chlorosulfolipids found in freshwater algae are the same as the analogous lipids of O. danica, but others have some distinctive features, including a chlorovinylsulfate group. Complex undecachlorosulfolipids, isolated from the digestive glands of toxic mussels, are causative agents of diarrhetic shellfish poisonings, which tend to be associated with marine algal blooms.

 

2.   Other Lipid Sulfates

Sphingolipid sulfates are extremely important for the function of the brain and kidney, amongst other tissues, and they have their own web page here. Similarly, seminolipid and cholesterol sulfate are important sulfur-containing lipids, which are discussed on other web pages on this site for reasons of their relevance to other topics. However, there remain some interesting lipid sulfates, which are of crucial importance to the organisms that produce them.

The only sulfated fatty acids to have been identified to date are the 'caeliferins', which were found in the oral secretions of a species of grasshopper. They are believed to elicit the release of volatile organic compounds as a defence response when the insects graze upon plants.

Structure of caeliferin A

The membranes of Mycobacterium tuberculosis contain sulfolipids consisting of a sulfated trehalose moiety to which up to four fatty acids are linked including three of the very-long-chain multibranched acids (hepta- and octamethyl phthioceranic and hydroxyphthioceranic acids), i.e. 2,3,6,6′-tetraacyl-α-α’-trehalose-2′-sulfates (see also our web page on mycolic acids and trehalose-containing lipids).

Sulfolipid from mycobacterium tuberculosis

 

3.   Taurolipids

A number of lipids have been found that are conjugated to taurine (ethanolaminesulfonic acid), of which the best known are certain bile acids, which are discussed elsewhere on this site as are N-acyltaurines of mammalian origin. Taurine itself is synthesised from cysteine via oxidation and decarboxylation reactions. It is very rare in plants but is plentiful in animal tissues, especially the brain. Aside from the bile acids, the first taurolipids to be recognized were novel C18 hydroxy acids (3, 4 or 5 hydroxyl groups) with an amide link to taurine, which were isolated from the ciliated protozoan Tetrahymena. The hydroxyl on carbon 3 is acylated with normal fatty acids (approx. 30% 16:0), and in one variant, carbon 7 is similarly acylated. The deacylated backbone has been termed ‘lipotaurine’.

Formula of a taurolipid
TaurolipidR1R2R3R4
taurolipid A OH OH H H
7-acyltaurolipid A CH3(CH2)14COO OH H H
taurolipid B OH OH OH H
taurolipid C OH OH OH OH
 

 

Biosynthesis is believed to involve conjugation of stearic acid with taurine, with subsequent sequential insertion of hydroxyl groups.

Recently, a biologically active taurine-containing lipid, termed 'irciniasulfonic acid B', was isolated from a marine sponge, Ircinia sp. This comprised 3-methyl-8-hydroxy-dec-2-enoic acid conjugated to taurine, with various unusual fatty acids linked to the hydroxyl group. In addition, a tauroglycolipid, 1,2-diacyl-3-glucuronopyranosyl-sn-glycerol taurineamide, was isolated from a seawater bacterium Hyphomonas jannaschiana, which has the further unusual feature of an absence of phospholipids. The main fatty acyl chains are saturated and monoenoic (C16 to C20).

Formulae of complex sulfonolipids

An unusual ganglioside, taurine-conjugated GM2, was isolated from brain samples from patients with Tay-Sachs disease, a well-known glycosphingolipid (GSL) storage disease. In this unusual lipid, the carboxyl group of N-acetylneuraminic acid is amidated by taurine. As this lipid is not present in normal brains, it seems probable that it is associated with the pathogenesis of the disease, possibly as a means of removing the excess of GM2 from the tissue.

 

4.   Other Sulfonolipids

The best known and most abundant of the sulfonolipids is sulfoquinovosyldiacylglycerol or 1,2-di-O-acyl-3-O-(6'-deoxy-6'-sulfo-α-D-glucopyranosyl)-sn-glycerol, which is a key component of the photosynthetic mechanism of higher plants and other photosynthetic organisms. Because of its biosynthetic and functional relationship to the mono- and digalactosyldiacylglycerols, it is discussed in those web pages.

In 1978, the marine diatom, Nitzschia alba, was found to contain a number of interesting sulfolipids as membrane constituents, i.e. 24-methylene-cholesterol sulfate, 1-deoxyceramide-1-sulfonate and phosphatidylsulfocholine (a sulfonium analogue of phosphatidylcholine), in addition to sulfoquinovosyldiacylglycerol. The last is present in an amount comparable to that in higher plants, although the organism is not photosynthetic.

Formulae of 1-deoxyceramide-1-sulfonate and phosphatidylsulfocholine

1-Deoxyceramide-1-sulfonate consists of a long-chain base, analogous to sphingosine but with a sulfonate moiety attached to carbon 1. The predominant fatty acid (64%) is trans-3-hexadecenoic acid, which is normally associated with the phosphatidylglycerol of plant chloroplasts. Experiments with 35S-cysteine or cystine labelled the deoxyceramide sulfonate and phosphatidylsulfocholine, but not the sterol sulfate nor the sulfoquinovosyldiacylglycerol. The illustration show negatively charged molecules but there will of course be balancing cations under natural conditions.

Phosphatidylsulfocholine, with two methyl groups attached to the sulfur atom as opposed to three attached to nitrogen, completely replaces phosphatidylcholine in Nitzschia alba. However, it has subsequently been found in other marine diatoms and algae that also contain phosphatidylcholine. Experiments with isotopically labelled substrates in Nitzschia alba confirmed that both methyl groups and the sulfur atom were derived from methionine.

Subsequently, a sulfonic acid derivative of ceramide, N-fatty acyl capnine or capnoid, was described as a major lipid component of gliding bacteria of the genera Cytophaga, Capnocytophaga, Sporocytophaga, and Flexibacter. These are organisms that are able to move over solid surfaces, but not through liquids, although they do not appear to have flagella or other organs of propulsion. Capnine is 2-amino-3-hydroxy-15-methylhexadecane-1-sulfonic acid and occurs in the organisms both in the free form and as N-acylated derivatives, though up to 20% of other homologues can occur, depending on species. The fatty acids are much more heterogeneous and vary from C14 to C16 in chain length, a high proportion with iso- or anteiso-methyl branches and hydroxyl groups in positions 2 and 3. Related compounds, termed sulfobacins A and B, i.e. (2R,3R)-3-hydroxy-2-[(R)-3-hydroxy-15-methylhexadecanamido]-15-methylhexadecanesulfonic acid and (2R,3R)-3-hydroxy-15-methyl-2-[13-methyltetradecanamido]-hexadecanesulfonic acid, respectively, have been found in Chryseobacterium sp. Similar lipids have been found in the gram-negative, seawater bacterium Cyclobacterium marinus.

capnine and halocapnine - formulae

Recently, a new sulfonolipid with some structural affinity to the capnoids has been isolated from the halophilic bacteria Salinibacter ruber and Salisaeta longa. It has the structure 2-carboxy-2-amino-3,4-hydroxy-17-methyloctadec-5-ene-1-sulfonic acid for which the trivial name halocapnine is suggested. As its 3-O-acyl derivative (and not N-acyl), it represents about 10% of the total cellular lipids of the former.

The experimental evidence suggests that biosynthesis of capnine occurs by the condensation of 13-methylmyristoyl-coenzyme A with cysteic acid, in a manner analogous to the condensation of palmitoyl-coenzyme A with serine during the biosynthesis of sphingoid bases. The function of capnoids is obscure, but there are suggestions that they may have a role in the motility of the organisms.

 

Recommended Reading

  • Anderson, R., Kates, M. and Volcani, B.E. Identification of the sulfolipids in the non-photosynthetic diatom Nitzschia alba. Biochim. Biophys. Acta, 528, 89-106 (1978) (DOI: 10.1016/0005-2760(78)90055-3).
  • Bedke, D.K. and Vanderwal, C.D. Chlorosulfolipids: Structure, synthesis, and biological relevance. Nat. Prod. Rep., 28, 15-25 (2011) (DOI: 10.1039/C0NP00044B).
  • Bisseret, P., Ito, S., Tremblay, P.A., Volcani, B.E., Dessort, D. and Kates, M. Occurrence of phosphatidylsulfocholine, the sulfonium analog of phosphatidylcholine in some diatoms and algae. Biochim. Biophys. Acta, 796, 320-327 (1984) (DOI: 10.1016/0005-2760(84)90133-4).
  • Corcelli, A., Lattanzio, V.M.T., Mascolo, G., Babudri, F., Oren, A. and Kates, M. Novel sulfonolipid in the extremely halophilic bacterium Salinibacter ruber. Appl. Env. Microbiol., 70, 6678-6685 (2004) (DOI: 10.1128/AEM.70.11.6678-6685.2004).
  • Godchaux, W. and Leadbetter, E.R. Sulfonolipids of gliding bacteria. Structure of the N-acylaminosulfonates. J. Biol. Chem., 259, 2982-2990 (1984).
  • Haines, T.H. Anionic lipid headgroups as a proton-conducting pathway along the surface of membranes: A hypothesis. Proc. Natl Acad. Sci. USA, 80, 160-164 (1983).
  • Kaya, K. Chemistry and biochemistry of taurolipids. Prog. Lipid Res., 31, 87-108 (1992) (DOI: 10.1016/0163-7827(92)90017-D).
  • Li, Y.T., Maskos, K., Chou, C.W., Cole, R.B. and Li, S.C. Presence of an unusual GM2 derivative, taurine-conjugated GM2, in Tay-Sachs brain. J. Biol. Chem., 278, 35286-35291 (2003) (DOI: 10.1074/jbc.M306126200).

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Updated March 4, 2013