These lipids (known also as diglycerides) are
fatty acid diesters of glycerol and occur in two isomeric forms:
R and R' are saturated or
unsaturated hydrocarbon chains.
Diacylglycerols are generated mainly during digestion in the stomach and in the duodenal
part of the intestine. In man, the lingual lipase preferentially hydrolyzes the ester bond
in the sn-3 position of the triacylglycerols, thus generating sn-1,2-diacylglycerols.
These molecules are isomerized in acidic solution with generation of
sn-1,3-diacylglycerols which again are hydrolyzed in monoacylglycerols commonly found in
the stomach content. In the duodenum as in the test tube, the lipase hydrolyzes easily the
triacylglycerol ester bonds at the sn-1 and sn-3 positions giving a mixture of sn-2,3 and
sn-1,2-diacylglycerols which again undergo chemical isomerization. In vitro, the
isomerization is subject to both acid and base catalysis, and is particularly
troublesome in the preparation of 1,2-diacylglycerols.
This process is used to do stereospecific analyses of triacylglycerols. More accurately, a
non specific procedure is now used to generate diacylglycerols: the reaction with the
Grignard reagent ethyl magnesium bromide which give all the possible combinations of
diacylglycerols.
In cell biology, diacylglycerols are generated from phospholipids, the acyl chains being
in the sn-1 and 2 positions. In lipid extracts, sn-1,3-diacylglycerols are always present,
even in lower amounts than the other form, because of an artefactual isomerisation during
isolation and purification. In cell extracts, diacylglycerol molecules have generally two
different fatty acid chains, the most unsaturated being found at the sn-2 position.
Diacylglycerols are important intermediates in the biosynthesis of triacylglycerols and
phospholipids and play a fundamental role in the cellular signalling. They are able to
activate cellular mechanisms directly via protein activation or indirectly via the
liberation of fatty acids which may be metabolized in agonist molecules (eicosanoids). The most famous molecular species of
diacylglycerol generated by phospholipase C from phosphatidyl inositol is
1-stearoyl-2-arachidonoyl-sn-glycerol. Diacylglycerols are recognized by a well
conserved protein motif, the C1 domain. It was observed for the first time in
protein kinases C but is present also in many other enzyme proteins.
Furthermore, diacylglycerols are able to modulate the biophysical properties of
biomembranes (Gomez-
Fernandez JC et al., Chem Phys Lipids 2007, 148, 1).
Diacylglycerols are the main components
of new cooking oils (ex: Econa, Kao
corp.). These oils are proposed to slow the increase of postprandial blood triglycerides
to help prevent the accumulation of body fat and high blood cholesterol levels
by increasing energy expenditure (review in Yanai
H et al., Nutr J 2007, 6:43).
Cyclic glycerol esters (tethered lipids) have been isolated from the
fruits of the Mediterranean plant Thapsia garganica (Apiaceae) (Liu
H et al., J Nat Prod 2004, 67,1439). These diacylglycerols have two of the
oxygens of glycerol included in a macrocyclic ring "macrocyclic
lipids", the cyclic chain having 18 carbon atoms.
These tethered lipids
are unprecedented in the plant kingdom.
Several terpenoic diacylglycerols have been isolated from nudibranch mollusks.
Thus, in Archidoris montereyensis, diacylglycerols with the structure of the terpenoic
monoglycerides, also described in these animals, but with acetylation of one
of the free hydroxyl groups of the glycerol molecule (Gustafson K et al.,
Tetrahedron 1985, 41, 1101) . Similar acetylated compounds, but with the double bond
confined in the B-ring between the carbon 5 and 6, were isolated in Archidoris
verrucosa (Cimino G et al.,
Tetrahedron 1988, 44, 2301). These compounds, which were named verrucosin A
and B, may contribute to the survival of the
nudibranch in predator-rich areas as they are highly ichthyotoxic, others having
feeding-deterrent properties.
Verrucosin A (R1=H, R2=COCH3)
and B (R1=COCH3, R2=H)
An unusual diacylglycerol, archidorin, has been isolated from the mantle of Archidoris tuberculata (Cimino G et al., J Nat Prod 1993, 56, 1642). Glycerol is esterified with tiglic acid (2-methylbut-2-enoic acid) and a diterpenoid clerodane acid at positions sn-1 and sn-2, respectively. Further studies on the Antarctic nudibranch (Austrodoris kerguelenensis) have characterized similar structures but with a diterpenoid moiety (of the clerodane or halimane type) at C-2 of glycerol and linked to an acetyl group at C-1 or C-3 (Gavagnin M et al., Tetrahedron 2003, 59, 5579).
In vegetals, phenolic diacylglycerols have been described. Thus, 1,3-diferulylglycerols have been described in the fruits of Aegilops, a Gramineae which is considered as the ancestors of the cultivated wheat (Cooper R et al., Phytochemistry 1978, 17, 1673). In one form, the two ferulic groups are methylated (see figure below), in the other, only one ferulic group is methylated.
1,3-Diferulylglycerol
While eubacteria, plants and animals contain largely
diacylglycerol-derived lipids, unusual dialkylglycerols are found in the membranes
of many thermophilic bacteria.
Non-isoprenoid dialkyl glycerol tetraether have been detected in peats but their
biological origin is as yet unknown (JS Sinninge Damste et al., 2000, Chem
Commun 1683). Similar structures have been described in the genus Thermotoga,
thermophillic bacteria of the order Thermotogales (Sinninghe Damste JS
et al., Arch Microbiol 2007, 188, 629). These bacteria are commonly found in
solfatara springs and in deep-sea marine hydrothermal systems. These lipids
consist of two glycerol units connected by two (C32) dimethyl chains derived
from diabolic acid
(15,16-dimethyltriacontanedioic acid), this acid being also present in these
bacteria.
Dialkyl
glycerol tetraether
Other
parent compounds are also present in Thermotogales, they have one to
three ester bonds instead of ether bonds. As these bacteria appeared early
during the evolution of life on Earth, it may be hypothesized that ether and
ester glycerol membrane lipids developed relatively early during evolution.
It must be emphasized that the stereochemistry of the glycerol backbone is
1,2-di-O-alkyl-sn-glycerol.
More branched lipids have been described in Archaea
(previously Archaebacteria), organisms living in extremely halophilic conditions or in hot
and acid springs in deep oceanic waters (Kates M Prog Chem Fats Lipids 1978, 15, 301;
Kates M et al., The biochemistry of archaea, Elsevier 1993). These
lipids consist of derivatives of a C20,C20-isopranyl glycerol diether (diphytanylglycerol
diether) and its dimer (dibiphytanyldiglycerol tetraether). The O-alkyl chains have a
branched structure deriving from phytanic
acid. In contrast with the structures observed in bacteria, the
stereochemistry of the glycerol backbone in Archaea is 2,3-di-O-alkyl-sn-glycerol.
The simplest structure (diphytanylglycerol diether) is now called archaeol.
This molecule structure, discovered in extremely halophilic bacteria (Kates M, Prog
Chem Fats other Lipids 1978, 15, 301), is found either free or in phospholipid-bound
forms.
The more complex tetraether structures (dibiphytanyldiglycerol tetraether) known as caldarchaeol, have been found in membranes from thermoacidophiles and methanogenic bacteria (Langworthy TA, Biochim Biophys Acta 1977, 487, 37).
This structure may also contain one to four
cyclopentane rings in each of the C40 biphytanyl groups. These tetraethers
(crenarchaeols) are present in marine crenarchaeota, an ubiquitous and abundant
component of plankton. It has been shown that the number of cyclopentane rings
is linearly correlated to the water temperature (Schouten S et al., Earth
Planet Sci Lett 2002, 204, 265)..
It is noticeable that extreme halophiles contain only archaeol-derived lipids, the
methanogens bacteria contain both archaeol- and caldarchaeol-derived lipids, and the
thermoacidophiles contain largely caldarchaeol-derived lipids.
Unsaturated terpenoid chains were found in Thermococcus hydrothermalis, an Archaea
living in deep-sea hydrothermal vents (Lattuati A et al., Lipids 1998, 33, 319).
These lipids have been discovered in peat bogs and soils and a survey of their
distribution in various locations has shown that they can be used in
palaeoenvironmental studies to estimate annual mean air temperature and soil pH
(Weijers J et al., Geochem Cosmochim Acta 2007, 71, 703).
