The Lipid Library

MISCELLANEOUS SULFO- AND SULFONOLIPIDS

STRUCTURE, OCCURRENCE AND BIOCHEMISTRY

1.   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 sulfolipids, which are discussed on other webpages on this site for reasons of their relevance to other topics. However, there remain a number of interesting lipid sulfates, which are of crucial importance to the organisms that produce them.

For example, 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 is 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 6 chlorine atoms in various positions. They constitute approximately 15% of the total lipids, but 90% of the polar lipids of the flagella. A considerable number of such compounds have been characterized from this organism, and some representative examples are illustrated. The relative stereochemistry of the major component, 'danicalipin A' (the last illustrated), has been determined.

Many aspects of the biosynthesis of unusual lipids remain to be confirmed, but it is believed that oleate is hydroxylated at C10, and then undergoes two C₂ additions via fatty acid elongases 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 by chlorinases. 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 suggests that two internal sulfate moieties share a single proton via a hydrogen bond. 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 related chloro- and bromosulfolipids have been found in algae and other organisms, and as toxins affecting shellfish.

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 defense response when the insects graze upon plants.

2.   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 non-photosynthetic.

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 labeled 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 from 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, sea-water bacterium Cyclobacterium marinus.

The experimental evidence suggests that biosynthesis of capnine in these bacteria 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.

Recently, a new sulfonolipid with some structural affinity to the capnoids, has been isolated from a halophilic aerobic bacterium, Salinibacter ruber. It has the structure 2-carboxy-2-amino-3-O-(13'-methyltetradecanoyl)-4-hydroxy-18-methylnonadec-5-ene-1-sulfonic acid, and represents about 10% of the total cellular lipids.

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. 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 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’.

Taurolipid	R1	R2	R3	R4
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).

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.

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).
• 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).
• 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).
• 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. Sulfolipids and halosulfolipids. In: Lipids and Biomembranes of Eukaryotic Organisms. pp. 197-232 (Ed. J.A. Erwin, Academic Press, N.Y.) (1973).
• 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).
• 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).

	Scottish Crop Research Institute (and MRS Lipid Analysis Unit), Invergowrie, Dundee (DD2 5DA), Scotland.		Right click on the icon to open in a new window
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