Glycosyldiacylglycerols & Related Lipids from Animals

1.  Mono- and Diglycosyldiacylglycerols

Following the discovery of mono- and digalactosyldiacylglycerols in plants, a search began for similar lipids in animal tissues (for the formulae, see our web pages on plant glycoglycerolipids). They are now known to be ubiquitous if minor components of brain and other nervous tissues, usually amounting to only 0.1 to 0.6% of the total lipids, and they can occur in trace amounts in other tissues. However, they are often overlooked in studies of animal glycolipids, as they are minor components relative to the glycosphingolipids, and can be inadvertently destroyed during some of the isolation procedures for the latter.

They exist in both diacyl and alkyl acyl forms, and contain mainly saturated and monoenoic fatty acid components, with 16:0, 18:0 and 18:1 comprising 90% or more of the total. The alkyl moieties consist of 70% or more of 16:0. The monogalactosyldiacylglycerol of mammalian brain is similar to that of plants, i.e. it is 1,2-di-O-acyl-3-O-β-D-galactopyranosyl-sn-glycerol (and the 1-alkyl,2-acyl form).

Structural formula of a monogalactosyldiacylglycerol

In fish brain, only the diacyl form is found, and it can be accompanied by related lipids in which the position 6 of the galactose unit is acylated, or in which an aldehyde is linked to the carbohydrate moiety via an acetal linkage. In contrast, little was known until recently of the digalactosyl equivalent. It has now been properly characterized (from a human carcinoma), and was found to be distinctive in having a Galα1-4Gal linkage rather than Galα1-6Gal as in plants, i.e. it is 1-O-alkyl-2-O-acyl-3-O-(β-galactosyl(1-4)α-galactosyl)-sn-glycerol.

Subsequently, related lipids but with glucose rather than galactose were found in saliva, bronchial fluid and gastric secretions. The lipid portion is 1-O-alkyl-2-O-acyl-sn-glycerol, with the fatty acid and alkyl constituents again being predominantly saturated. The carbohydrate moiety can consist of up to eight glucose units, with six being the most abundant. Although present at low levels only in absolute terms, these can comprise as much as 20% of the total lipids in saliva.

The biosynthesis of the galactosyldiacylglycerols has been studied in vitro with the microsomal fraction from brain tissue, but limited information only is available. There appear to be some similarities to the mechanism in plants in that there is an enzyme that catalyses the transfer of galactose from UDP-galactose to diacylglycerol.

The function of such galactolipids is still a matter for conjecture. They probably have a role in myelination, and may also have a function in cell differentiation and intracellular signalling. The glucolipids in saliva and related secretions may be involved in a defense mechanism against microbial attack.

 

2.  Seminolipid

As the name suggests, seminolipid or sulfogalactosylglycerolipid or 1-O-hexadecyl-2-O-hexadecanoyl-3-O-β-D-(3'-sulfo)-galactopyranosyl-sn-glycerol was first found in mammalian spermatozoa and testes, where it can amount to 3% of the total lipids and 90% of the glycolipids, and where it is located primarily in the outer leaflet of the plasma membrane. It is unusual in this tissue in a number of ways, not least in that it exists largely as a single molecular species, it is fully saturated, and it co-exists with other phospholipids that are highly unsaturated. It is now known to be present at low levels in many other animal tissues, especially those rich in glycolipids such as myelin and other nervous tissues.

Structural formula of seminolipid

However, there may then be some variation in the acyl and alkyl moieties. For example, the lipid portion can contain alkylacyl-, diacyl- and dialkylglycerol moieties, and the relative proportions and compositions can change somewhat with aging. In the mouse at least, different molecular species are located in different regions of the spermatogenesis apparatus, i.e. the major species (16:0-alkyl-16:0-acyl) is in tubules, while 16:0-alkyl-14:0-acyl and 14:0-alkyl-16:0-acyl species are in spermatocytes mainly, with the 17:0-alkyl-16:0-acyl species in spermatids and spermatozoa. There can be some limited variation in the chain lengths of the aliphatic components, but they are usually saturated. Fish brain is an exception, where the diacyl form predominates with 16:0 and 18:1 fatty acids.

The polar head group is identical to that of the cerebroside sulfate in myelin, and many other parallels can be drawn between the biosynthesis, metabolism and function of seminolipid and sphingolipid sulfates. Seminolipid is synthesised by sulfation of its precursor, galactosylalkylacylglycerol, by the action of 3-phosphoadenylylsulfate:cerebroside 3-sulfotransferase, i.e. the same enzyme that is involved in the synthesis of the analogous sphingolipid (3'-sulfo-galactosylceramide). Indeed, the precursor is also synthesised by a sphingolipid enzyme - ceramide galactosyltransferase. The process of sulfation is reversed by arylsulfatase A, the enzyme missing in patients suffering from metachromatic leukodystrophy.

There is abundant evidence from experiments with genetically modified animals that seminolipid is essential for germ cell function and spermatogenesis in the testis. It participates in the formation of lipid rafts in the sperm head, and is involved in sperm-egg binding at the plasma membrane.

 

3.  Glycosylglycerol Lipids from Sponges

A number of novel and interesting glycosylglycerol derivatives have been isolated from primitive members of the animal kingdom, such as sponges and corals. For example, new glycolipid analogues in which the sugar moiety is replaced by an unusual five-membered cyclitol were first found in the sponge Pseudoceratina crassa and termed ‘crasserides’. They are now known to occur more widely in sponges.

A crasseride

A branched-chain alkyl moiety is ether-linked to position 1 of the glycerol moiety, while position 2 can contain one of several fatty acids. They are believed to be natural deterrents against fish predation.

Even more unusual glycolipids containing sugar moieties linked to both positions sn-2 and -3 of glycerol together with an O-alkyl ether chain at position sn-1 were isolated from the sponge Myrmekioderma sp. and named ’myrmekiosides’. A similar lipid with two xylose units linked to glycerol and a vinyl ether linked alkyl group was found in the sponge Trikentrion loeve. In addition, ether-linked glycolipids with a sugar moiety in position sn-2, i.e. (2R)-1-hydroxy-3-hexadecyloxy-propyl-β-D-arabinopyranoside, were characterized in a soft coral Lobophytum crassum.

 

4.  Analysis

Glycosyldiacylglycerols tend to be present in animal tissues at such low levels that isolation and analysis present particular problems. Indeed, they have often been ignored by scientists with an interest in glycosphingolipids, because the methodology used for the latter can be destructive to O-acyl lipids. Azure A, a cationic dye that reacts with anionic lipids, is often employed to quantify seminolipid in reproductive tissues, though it lacks sensitivity and specificity. Electrospray-ionization tandem mass spectrometry now appears to hold particular promise for structural analyses.

 

Suggested Reading

  • Ishizuka, I. Chemistry and functional distribution of sulfoglycolipids. Prog. Lipid Res., 36, 245-319 (1997) (DOI: 10.1016/S0163-7827(97)00011-8).
  • Kongmanas, K., Xu, H.B., Yaghoubian, A., Franchini, L., Panza, L., Ronchetti, F., Faull, K. and Tanphaichitr, N. Quantification of seminolipid by LC-ESI-MS/MS-multiple reaction monitoring: compensatory levels in Cgt+/- mice. J. Lipid Res., 51, 3548-3558 (2010) (DOI: 10.1194/jlr.D010116).
  • Murray, R.K. and Narasimhan, R. Glycoglycerolipids of animal tissues. In: Handbook of Lipid Research 6. Glycolipids, Phosphoglycolipids and Sulfoglycolipids, pp. 321-361 (1990) (ed. M. Kates, Plenum Press, NY).
  • Pahlsson, P., Spitalnik, S.L., Spitalnik, P.F., Fantini, J., Rakotonirainy, O., Ghardashkhani, S., Lindberg, J., Konradsson, P. and Larson, G. Characterization of galactosyl glycerolipids in the HT29 human colon carcinoma cell line. Arch. Biochem. Biophys., 396, 187-198 (2001).
  • Slomiany, B.L., Murty, V.L.N., Liau, Y.H. and Slomiany, A. Animal glycoglycerolipids. Prog. Lipid Res., 26, 29-51 (1987).
  • Tamai, Y., Nakamura, K., Takayama-Abe, K., Uchida, K., Kasama, T. and Kobatake, H. Less polar glycolipids in Alaskan pollack brain: isolation and characterization of acyl galactosyl diacylglycerol, acyl galactosyl ceramide, and acyl glucosyl ceramide. J. Lipid Res., 34, 601-608 (1993).
  • Zhang, Y., Hayashi, Y., Cheng, X., Watanabe, T., Wang, X., Taniguchi, N. and Honke, K. Testis-specific sulfoglycolipid, seminolipid, is essential for germ cell function in spermatogenesis. Glycobiology, 15, 649-654 (2005) (DOI: 10.1093/glycob/cwi043).

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Updated December 21, 2011