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Glycosyldiacylglycerols: 2. Animal Tissues



Following the discovery of mono- and digalactosyldiacylglycerols in plants, a search began for similar lipids in animal tissues. It soon became apparent that they were present at trace levels in most tissues, but especially brain, while more complex oligoglycosyldiacylglycerols are significant components of intestinal membranes. However, little appears to have been published in recent years on animal glycosyldiacylglycerols other than seminolipid discussed below. Many of the unusual glycosyldiacylglycerols reported from primitive animals such as sponges are now known to be products of symbiotic bacteria.


1.  Mono- and Diglycosyldiacylglycerols

Mono- and digalactosyldiacylglycerols 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 analysis of 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, relatively little is known of the digalactosyl equivalent, although it has been fully characterized (from a human carcinoma) and is 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.

Oligoglucosyldiacylglycerols: Related lipids but with glucose rather than galactose have been characterized from 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 8 glucose units, with six being the most abundant. Although present at low levels only in absolute terms, they 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 glycolipids 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 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

This lipid in male reproductive tissues is unusual in a number of ways, not least in that it exists largely as a single molecular species, i.e. with an ether-linked C16 alkyl group in position sn-1 and palmitic acid in position sn-2. Thus, it is fully saturated and co-exists with other phospholipids that are highly unsaturated. However, there can be some limited variation in the acyl and alkyl moieties depending on the tissue and species. 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-phosphoadenosine-5'-phosphosulfate:cerebroside 3-sulfotransferase, i.e. the same enzyme and sulfate donor that are involved in the synthesis of the analogous sphingolipid (3'-sulfo-galactosylceramide). Indeed, the glycolipid precursor is also synthesised by a sphingolipid enzyme - ceramide galactosyltransferase. The process of sulfation is reversed by the corresponding sphingolipid enzyme also, i.e. 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 testes. It participates in the formation of lipid rafts in the sperm head and contributes to the shape and stability of sperm cell membranes. In addition, it is involved in sperm-egg binding at the plasma membrane, and many proteins with an affinity to seminolipid have been identified. While it is evident that cell surface seminolipid molecules are important functionally in germ cell differentiation and in interactions with other cell types, little detailed information appears to be available.


3.  Glycosylglycerolipids 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'. These and related lipids occur more widely in sponges, but they are now known to be the product of symbiotic bacteria and not of the animals per se (some sponges can contain more bacterial than animal cells).

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, and similar lipids have been isolated from soft corals. It is possible that these also are of bacterial rather than animal origin, but this has yet to be investigated.


4.  Analysis

Glycosyldiacylglycerols tend to be present in animal tissues at such low levels that isolation and analysis presents real difficulties. Indeed, they are usually ignored by scientists with an interest in glycosphingolipids, because the methodology used to concentrate 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, although it lacks sensitivity and specificity. Electrospray-ionization tandem mass spectrometry now appears to hold particular promise for structural analyses.


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Lipid listings Credits/disclaimer Updated: May 2nd, 2017 Author: William W. Christie LipidWeb icon