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Betaine Lipids



Structure of betaineGlycerolipids containing an ether-linked betaine moiety occur naturally in lower eukaryotic organisms such as algae, bryophytes, fungi and some primitive protozoa, and in photosynthetic bacteria. They are not found in flowering plants, but have been detected in some spore-producing plants, such as ferns and species belonging to the Equisetophyta and related genera. In these lipids, the polar betaine group is linked by an ether bond at the sn-3 position of the glycerol moiety, with the fatty acids esterified in the sn-1 and sn-2 positions. There is no phosphorus or carbohydrate group, and some might prefer to classify such lipids with the complex lipoamino acids, but they are treated separately here because of their distinctive occurrence and function. The term "betaine" was originally applied to trimethylglycine (illustrated), first isolated from sugar beet, but it is now used generically for other N-trimethylated amino acids.

Three related lipids of this type have been described with differing trimethylated hydroxyamino acids linked to diacylglycerols through the ether bond. They have a positively charged trimethylammonium group and a negatively charged carboxyl group, and they are therefore zwitterionic at neutral pH. The three types of betaine lipid are 1,2-diacylglyceryl-3-O-4'-(N,N,N-trimethyl)-homoserine (sometimes abbreviated to DGTS), 1,2-diacylglyceryl-3-O-2'-(hydroxymethyl)-(N,N,N-trimethyl)-β-alanine and 1,2-diacylglyceryl-3-O-carboxy-(hydroxymethyl)-choline. Of these, the first is by far the most common in nature, and taxonomic studies suggest that it may have been the first lipid of this type to be formed during evolution. The alanine-derived lipid takes the place of DGTS in brown algae, e.g. Ochromonas danica, but is not found in green algae, while the third of these lipids is found in marine algae of the genus Haptophyceae, e.g. Pavlova lutheri. The fungus Heterospora chenopodii contains a monoacylglyceryltrimethylhomoserine in which the acyl moiety is a novel 3-keto fatty acid.

Formulae of the three main betaine lipids

In the diacylglyceryltrimethylhomoserine of most algae studied, the fatty acids in position sn-1 of the glycerol moiety tend to be saturated (mainly 14:0 and 16:0), while those in position 2 are C18 unsaturated (predominantly 18:2(n-6) and 18:3(n-3)). However, marine algae can contain high proportions of polyunsaturated fatty acids (e.g. 20:5(n-3)) in both positions. The fatty acid compositions and positional distributions within the glycerol moiety can be somewhat different from those in other glycerolipids such as phosphatidylcholine, as can be seen from the results in Table 1 for a Chlorella species, although this is dependent on the particular organism. Of the fatty acids in DGTS of Acanthamoeba castellanii, 87% is oleate (9-18:1).

Table 1. Stereospecific distribution of acyl moieties of phosphatidylcholine (PC) and DGTS between positions sn-1 and 2 of the glycerol backbone in a Chlorella species.
Lipid
class
Position Fatty acid composition (Mol %)
16:0 16:1 16:2 16:3 18:0 18:1 18:2 18:3 other
 
PC sn-1 14 2 2 1 2 60 8 9 2
sn-2 2 5 trace 4 trace 52 20 15 2
 
DGTS sn-1 46 5 trace 1 1 36 5 3 3
sn-2 14 3 7 6 3 34 17 14 2
Adapted from Weber, N. et al. J. Lipid Mediators, 1, 37-48 (1989).

There is an obvious similarity between the structures of betaine lipids and that of the zwitterionic glycerophospholipid phosphatidylcholine. Although the phase transition temperature for DGTS is slightly higher than that of phosphatidylcholine with an identical fatty acid composition, the physical phase behaviour of both lipids in mixtures with water is in general similar. There is appreciable evidence for an inverse relationship between the presence of betaine lipids and phosphatidylcholine in the membranes of some algae, phytoplankton, fungi and bacteria (but not in all), indicating that they can substitute for each other to a substantial extent, certainly in relation to membrane functions. This has been demonstrated in a variety of organisms, especially when phosphorus is a limiting nutrient. In the plant pathogen Agrobacterium tumefaciens, the increased formation of DGTS in this circumstance is accompanied by increases in the concentration of cyclopropyl fatty acid constituents in all lipids. The yeast Saccharomyces cerevisiae, in which the enzymes for DGTS biosynthesis are absent, has been genetically engineered so that phosphatidylcholine is completely replaced by DGTS although essential functions continue. Some data for the bacterial species Mesorhizobium loti (Rhizobiales) grown in phosphorus-replete and phosphorus-depleted conditions are listed in Table 2.

Table 2. Polar lipid composition (%) of Mesorhizobium loti grown under phosphate-replete (+P) and phosphate-depleted (-P) conditions
 Lipid class +P -P
 
 Glycosyldiacylglycerols - 10
 Diacylglycerol-trimethylhomoserine - 24
 Ornithine lipid 11 16
 Cardiolipin (+ unknown) 5 11
 Phosphatidylcholine 30 15
 Phosphatidylglycerol 17 14
 Mono- and dimethyl-phosphatidylethanolamine 38 10
Adapted from Devers, E.A. et al. J. Bacteriol., 193, 1377-1384 (2011);   DOI.

The biosynthesis of diacylglyceryl-N,N,N-trimethylhomoserine was first studied in phosphate-starved cells of the purple bacterium Rhodobacter sphaeroides. Two enzyme systems were identified as essential to the process, with the first (BtaA) transferring the 3-amino-3-carboxypropyl group of S-adenosylmethionine to the 3-hydroxyl of a 1,2-diacyl-sn-glycerol to form the intermediate diacylglycerylhomoserine. The second enzyme system (BtaB) transfers methyl groups from S-adenosylmethionine in three successive steps to form the final product diacylglyceryl-N,N,N-trimethylhomoserine. However, in the algal model Chlamydomonas reinhardtii, which produces DGTS to the exclusion of phosphatidylcholine regardless of phosphorus availability, a single bifunctional enzyme can carry out the complete synthesis.

Biosynthesis of betaine lipids

The ether bond linking the head group to the diacylglycerol moiety in betaine lipids is much stronger than the phosphoryl ester bond in phosphatidylcholine and is impervious to the phospholipases C and D, so it is unclear whether betaine lipids have any metabolic role in addition to their function in membranes, for example as a source of diacylglycerols. No enzyme that cleaves the ether bond has yet been identified, although presumably one must exist. On the other hand, there is evidence from experiments with algae that the betaine lipids are involved in the transfer of fatty acids from the cytoplasm to the chloroplast, and that they may be the primary acceptor of fatty acids formed de novo before they are processed and redistributed to other lipids. During nitrogen starvation, the acyl groups of betaine lipids may be utilized for triacylglycerol synthesis in the algae Phaeodactylum tricornutum. In C. reinhardtii, oleic acid esterified to DGTS can be desaturated to linoleic and linolenic acids (c.f. the same process in phosphatidylcholine of higher plants).

Like the choline-containing lipids, betaine lipids display a blue coloration when sprayed with Dragendorff reagent. However, they are not stained by the typical reagents used to detect lipid-bound phosphorus. They are usually identified by this means on examination by thin-layer chromatography. Modern mass spectrometric methods greatly facilitate analysis.


Related Lipids

A similar type of lipid but in which lysine is linked to 1,2-diacyl-sn-glycerol via an ester rather than an ether bond, i.e. lysyl-diacylglycerol, has been isolated from Mycobacterium phlei strain IST, with palmitic and tuberculostearic acids as the fatty acid constituents.

Figure 4. Formula of lysyl-diacylglycerol


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Lipid listings Credits/disclaimer Updated: May 23rd, 2017 Author: William W. Christie LipidWeb icon