This group consists of phosphorus-containing sphingolipids (mainly sphingomyelin) but containing a ceramide
linked to a phosphate group, itself esterified to a small polar
head group (choline, ethanolamine, glycerol). The simplest form, ceramide
phosphate, is an important bioactive molecule. The ceramide part is formed by a long-chain fatty acid
linked to the amino group (i.e. N-acyl or amide) of a long-chain base. Those containing also a glycoside moiety are considered elsewhere.
A group of analogues with a C-P bond instead of a C-O-P bond, the phosphonolipids,
are present in protozoa and invertebrates.
Ceramide-1-phosphate was first shown to be produced form sphingomyelin by
the sphingomyelinase D found in spider venom (Kurpiewski
G et al., Biochem Biophys Acta 1981, 678, 467). It was suggested that
the spider-induced dermonecrosis near the injection could result from an induced
platelet aggregation. Ceramide-1-phosphate was shown to be present for the first
time in human leukemia cells (30 pmol/106 cells) and metabolic
studies have demonstrated that he was produced by phosphorylation of ceramide by
a specific ceramide kinase (Dressler K et
al., J Biol Chem 1990, 265, 14917).
Later, ceramide-1-phosphate was shown to be a specific and potent inducer of
arachidonic acid and prostanoid synthesis in cells (Pettus
BJ et al., J Biol Chem 2003, 278, 38206) through the translocation and
activation of the cytoplasmic phospholipase A2 (cPLA2) (Pettus
BJ et al., J Biol Chem 2004, 279, 11320). Furthermore, it has been suggested that ceramide-1-phosphate and sphingosine-1-phosphate
may act in concert to regulate the production of eicosanoids,
the important inflammatory mediators (Chalfant
CE et al., J Cell Biol 2005, 118, 4605).
In sphingomyelin the
long-chain base is sphingosine, dihydrosphingosine (in animals) or phytosphingosine (in
plants). About two-thirds of the fatty acids found in grey matter sphingomyelin consist of
stearic acid while this proportion is formed by lignoceric (24:0) and nervonic (24:1)
acids in white matter of the brain. This phospholipid occurs in appreciable quantities in
brain (more than 10% of the total phospholipids), but in lesser quantities in other
tissues. An exception is the bovine erythrocyte where sphingomyelin forms about 50% of
total phospholipids.
Sphingomyelin
containing polyenic very-long chain fatty acids are present in testes and
spermatozoa of mammals. The composition of sphingomyelin differs between animal
types. Human spermatozoa contained n-6 fatty acids with 2 to 4 double bonds and
carbon chain lengths up to 32. In ram and bull testes and spermatozoa, n-3 and
n-6 fatty acids with 4, 5 and 6 double bonds with carbon chain lengths up to 34
are found. In rat and boar, the fatty acids are mainly of the n-6 series with 3
to 5 double bonds and carbon chain lengths up to 34. In the latter two animal
species, sphingomyelin may contain 2-hydroxylated fatty acids with 4 to 6 double
bonds and carbon chain lengths up to 34 (Robinson
BS et al., J Biol Chem 1992, 267, 1746). It has been determined
that in bull and ram spermatozoa, the very long-chain polyunsaturated fatty
acids were the major acyl groups (about 70%) of sphingomyelins and ceramides (Furland
NE et al., J Biol Chem 2007, 282, 18151). Experiments on cryptorchid rat
testes have shown that these lipids lost their characteristic long-chain and
very long-chain fatty acids, notably 22:5n-6 and 28:4n-6, which suggests that
these species are linked to the membranes of germ cells (Furland
NE et al., Biol Reprod 2007, 77, 181).
Until recently,
sphingomyelin has been thought to be an inert constituent of cell membranes, but current
studies suggest that metabolites of sphingomyelin are involved in the signal transduction
pathway. The turnover of sphingomyelin involves removal of the polar head,
phosphorylcholine, by various sphingomyelinases (phospholipase C-like), generating
ceramides or ceramide phosphates.
A sphingolipid analogue of phosphatidylethanolamine, ceramide
phosphorylethanolamine, has been reported for the first time in the
housefly, Musca domestica (Crone HD et al., Biochem J 1963, 89, 11).
The initial finding of this lipid in bacteria was made in Bacteroides ruminicola
(Kunsman JE et al., Abst Amer Chem Soc 1966, 152nd meeting, C-255).
Shortly later, its correct composition was described and evidence was reported
that this sphingolipid represented a significant proportion of the lipids (about
half of phospholipids) in another anaerobe, Bacteroides melanogenicus
(now Prevotella melaninogenica) (LaBach JP et al., J Lipid Res 1969,
10, 528). Their base appears to have branched or normal saturated carbon
chains of 17, 18, or 19 atoms, their fatty acid having a high percentage of
14:0, 17:0, or 18:0 acid. That analogue of phosphatidylethanolamine was
reported for the first time in rumen protozoa in 1967 (Dawson RM et
al., Biochem J 1967, 105, 837).
This sphingolipid was reported to be also present in snails, marine bivalves (Itasaka O et al., J Biochem 1973, 73,
191), insects (Malgat et al., J Lipid
Res 1986, 27, 251) but also in chicken and rat liver (Muehlenberg BH et
al., Can J Biochem 1972, 73, 191). It was recently identified in some pathogen fungi (Oomycetes)
where its
structure was ascertained by mass spectrometry and NMR spectrometry (Moreau RA et al., Lipids
1998, 33, 307). The most abundant molecular species contained a 16-carbon di-OH sphingoid
base and erucic acid (22:1 n-9) as the amide-linked fatty acid. Other fatty acids were
found: 16:0, 18:0, and 22:0. In another fungi, the long-chain base was determined to be an
unusual 19-carbon branched tri-unsaturated sphingoid. It was also extensively
studied in lipid extracts from several species of Sphingobacterium (Naka
T et al., Biochim Biophys Acta 2003, 1635, 83)
ceramide
phosphorylethanolamine
Ceramide phosphorylglycerol
has been isolated from lipid extracts of an anaerobic bacterium Bacteroides
melaninogenicus (LaBach JP et al., J Lipid Res 1969, 10, 528). The
long-chain bases appear to have branched (17:0 and 18:0) and normal (18:0)
saturated carbon chains while the amide-linked fatty acids have a high
percentage of 14:0, 17:0 and 18:0. The presence of this rare lipid, similar to phosphatidylglycerol
found extensively in bacteria, has been confirmed later in other Bacteroides
species (Kato M et al., Anareobe 1995, 1, 135).
Phosphono analogs of ceramide phosphorylethanolamine have been described
particularly in marine invertebrates such as molluscs and medusa. The first
evidence for the occurrence of a phosphonolipid in living materials was that of
a ceramide aminoethylphosphonate extracted from a sea anemone, Anthropleura
elegantissima (Rouser G et al., JAOCS 1963, 40, 425).
The main phosphono compounds that have been found are ceramide aminoethylphosphonate and its methylated analog ceramide N-methylaminoethylphosphonate.
The most abundant fatty acid bound to the amino group is C14 or C16.
N-(tetradecanoyl)-sphing-4-enine-1-(2-aminoethylphosphonate)
The distribution of these lipids in
lower animals may be an important indicator in the phylogenetic field (Hori T
et al., Prog Lipid Res 1993, 32, 25). Sphingophosphonolipids have been found
in Pelagia noctiluca (Kariotoglou DM et al., Comp Biochem Phys B 2003,
136, 27) and in Aurelia aurita (Kariotoglou DM et al., Lipids
2001, 36, 1255). However, these reports did not provide any detailed
information on their structure. The structure of one ceramide aminoethylphosphonate found in the medusa Phyllorhiza punctata has been described (de
Souza LM et al., Chem Phys Lipids 2007, 145, 85).
A metabolite of sphingomyelin, sphingosylphosphorylcholine, has been shown to be a
potentially important lipid mediator in several tissues and immune system. The
first description of a remarkably potent mitogenic activity was demonstrated in
1991 (Desai
NN et al., Biochem Biophys Res Comm 1991, 481, 361).
Sphingosylphosphorylcholine
Research has demonstrated that this lyso-phospholipid has no specific receptor but, likely via the sphingosine-1-phosphate receptor, can act as a mitogen and may be also a pro-inflammatory mediator (Nixon GF et al., Prog Lipid Res 2008, 47, 62).
