Inositol-containing lipids have been reported as early as 1930 in
Tuberculosis bacilli (Anderson RJ, J Am Chem Soc 1930, 52, 1607) and later in
soybean lipids (Klenk E et al., Z Physiol Chem 1939, 258, 33). Folch
(J Biol Chem 1942, 146, 35) reported fort the first time the existence of an
inositol containing phospholipid in an animal tissue, the brain. This compound in a very
crude form was isolated from the "cephalin"
fraction of brain phospholipids thanks to its lower solubility in ethanol than
phosphatidylethanolamine and phosphatidylserine. Its structure was elucidated later (Pizer
et al., J Am Chem Soc 1959, 81, 915). Soon after, the occurrence of higher
phosphorylated parent compounds was reported. Now, three major inositol-containing
phospholipids are known in mammalian cells.
The basic phosphatidylinositol (Ptd Ins) is
1,2-diacyl-sn-glycero-3-phospho-1-D-myo-inositol (formerly monophosphoinositide).
The later is also found with an additional phosphate esterified to the 4
position of the inositol. This compound is known as phosphatidylinositol 4-phosphate or
PtdIns(4)P (formerly diphosphoinositide)
P
on the inositol ring is for -PO3H2
Another phosphatidylinositol monophosphate has been described in
plants, phosphatidylinositol 5-phosphate or
PtdIns (5)P (Meijer
HJ et al., Biochem
J. 2001, 360, 491). PtdIns(5)P is considered now as a general plant
lipid that represents a significant proportion of the phosphatidylinositol pool.
The increase of its concentration in cells to hyperosmotic stress suggests a
role in osmotic-stress signaling.
Evidence also indicates a role for PtdIns(5)P in regulating cellular
phosphatidylinositol PtdIns(3,4,5)P levels. PtdIns(5)P might activate the PI
3-kinase pathway (Carricaburu
V et al., Proc Natl Acad Sci U S A 2003, 100, 9867). A
new role for PtdIns(5)P in the regulation of membrane transport from late
endosomal compartments to the plasma membrane was also proposed (Lecompte
O et al., Trends Biochem Sci 2008, 33, 453).
PtdIns(4)P can be also esterified at the position 5 of the inositol by an
additional phosphate group. This compound is known as phosphatidylinositol
4,5-bisphosphate or
PtdIns(4,5)P2 (formerly triphosphoinositide).
This
phospholipid is of major importance since, after phospholipase C hydrolysis, a water
soluble molecule (inositol 1,4,5-P) is formed which plays a fundamental role in cell
signaling. The other part of the molecule, the diacylglycerol, is also involved directly
in the activation of protein kinase C and indirectly in the eicosanoid cascade by the
liberation of arachidonic acid (major fatty acid present at position 2 in all
phosphatidylinositols and liberated by phospholipase A2 action).
Phosphatidylinositol 4,5-bisphosphate may be also considered a signaling
molecule in its own right since the demonstration of its involvement in the
regulation of sodium/calcium exchangers and potassium channels (Hilgemann
DW, J
Physiol 2007, 582, 903).
Because of their acidic nature, all the inositol phospholipids occur as
salt associations with Na, K and Ca and need acidic conditions during their extraction to
prevent trapping in the protein matrix.
Recently, identification of other inositol phospholipids was reported. These derivatives
have a different phosphorylation pattern since they are defined as PtdIns(3)P, PtdIns(3,4)P2 and PtdIns(3,4,5)P3. While present at very low concentrations, they appear to
have important functions in cell biology.
A graphical chart of the biosynthesis of inositol phospholipids may be found on
the BioCarta
web site.
A new phosphatidylinositol was
characterized in the opportunistic pathogen Corynebacterium amycolatum. It was
identified as acyl-phosphatidylinositol containing a saturated fatty acyl chain
(mainly C16:0) on the inositol moiety (as 3-O-acyl) (Valero-Guillen
PL et al., Chem Phys Lipids 2005, 133, 17). This acylation position of
the inositol appears identical to that described in the other complex
inositol-containing molecules (acyl-phosphatidylinositol mannosides) found in mycobacteria.
Dialkyl phosphatidylinositols have been described for the first time in a
myxobacterium, Stigmatella aurantiaca (Caillon
E et al., J Bacteriol 1983, 153, 1348) and later in a protozoan parasite
of man, Leishmania mexicana (Singh
BN et al., Biochem Biophys Res Comm 1988, 157, 1239).
