PHOSPHATIDYLINOSITOL: STRUCTURE, FORMATION, FUNCTIONS - BIOLOGY - 2025

The phosphatidylinositol is a phospholipid family of glycerophospholipids or phosphoglycerides, which are present in biological membranes. It makes up about 10% of the total phospholipid content in an average cell.

It is common on the inside of the plasma membrane of many eukaryotes and prokaryotes. In mammals and other vertebrates, it especially enriches the membranes of brain cells; and it was in these tissues that it was first observed by Folch and Wooley in 1942.

Classical representation of phosphatidylinositol (Source: NEUROtiker via Wikimedia Commons)

Its chemical structure, as well as that of some of its phosphorylated derivatives, was determined by Ballou's research group between 1959 and 1961.

It has important structural functions, related to its abundance in the membranes, but it is also an important source of second messengers that have important implications in cellular signaling processes that are triggered by numerous and diverse special stimuli.

Its glycosylated form participates in the covalent modification of proteins that allows them to bind to membranes through lipid structures called GPI (glycosylphosphatidylinositol) “anchors”.

Structure

Like most membrane lipids, phosphatidylinositol is an amphipathic molecule, that is, it is a molecule with a hydrophilic polar end and a hydrophobic non-polar end.

Its general structure is based on a 1,2-diacyl glycerol 3-phosphate backbone, where the two fatty acid chains esterified at the carbons at positions 1 and 2 represent the apolar tails, and the phosphate group, attached to the group " head ”, represents the polar region.

Head group: inositol

An inositol molecule attached via a phosphodiester bond to the phosphate group at the carbon at position 3 of the glycerol molecule represents the "head" group of this phospholipid.

Inositol is a derivative of cyclohexane that has all its carbon atoms (6) each linked to a hydroxyl group. It can come from foods consumed in the diet, from the de novo synthesis route, or from its own recycling. Brain cells, as well as other tissues to a lesser extent, produce it from glucose 6-phosphate.

The structure of many of the phosphatidylinositol derivatives is nothing more than a phosphatidylinositol molecule to which phosphate groups have been added in some of the hydroxyl groups of the inositol portion.

Apolar tails

The hydrocarbon chains of the apolar tails can have varying lengths from 16 to plus or minus 24 carbon atoms, depending on the organism in question.

These chains can be saturated (carbon-carbon single bonds) or unsaturated (carbon-carbon double bonds; monounsaturated or polyunsaturated) and, like other phospholipids derived from phosphatidic acid, that of the fatty acid in the C2 position of glycerol 3-phosphate it is usually unsaturated.

These lipids usually have fatty acid chains corresponding to stearic acid and arachidonic acid, of 18 and 20 carbon atoms, one saturated and the other unsaturated, respectively.

Training

Phosphatidylinositol, like other phospholipids, is formed from phosphatidic acid, a simple phospholipid whose structure is characterized by two apolar tails and a polar head composed only of the phosphate group attached to the carbon at position 3 of glycerol.

De novo synthesis

For the de novo formation of phosphatidylinositol, phosphatidic acid reacts with CTP (cytidine triphosphate), a high-energy molecule analogous to ATP, and forms CDP-diacylglycerol, which is a common precursor in the phosphatidylinositol pathway and its derivatives, of phosphatidylglycerol and diphosphatidylglycerol or cardiolipin.

The reaction in question is catalyzed by the enzyme CDP-diacylglycerol synthase, which has a dual subcellular location that involves the microsomal fraction and the inner mitochondrial membrane.

Phosphatidylinositol subsequently arises from a condensation reaction between an inositol molecule and a CDP-diacylglycerol molecule resulting from the previous step.

This step is catalyzed by a phosphatidylinositol synthase (CDP-diacylglycerol: myoinositol 3-phosphatidyl transferase), an enzyme associated with the membrane of the endoplasmic reticulum of mammalian cells.

The reaction that represents the limiting step of this process is actually the formation of inositol from glucose 6-phosphate, which must occur "upstream" of the biosynthetic pathway.

Synthesis of its derivatives

The phosphorylated derivatives of phosphatidylinositol are produced by a group of enzymes called phosphatidylinositol kinases, which are responsible for attaching phosphate groups to the hydroxyl groups of the inositol portion of the parent lipid.

Features

Structural

Like phosphatidylserine and phosphatidylglycerol, phosphatidylinositol serves multiple functions. It has important structural implications, since it is part of the lipid bilayers that make up the different and multifunctional biological membranes.

Many proteins "bind" to cell membranes through what are called "GPI anchors", which are nothing more than glycosylated derivatives of phosphatidylinositol that provide proteins with a hydrophobic "anchor" that supports them on the surface of the cell. membrane.

Some proteins of the cytoskeleton bind to phosphorylated derivatives of phosphatidylinositol, and this type of lipid also serves as a nucleus for the formation of protein complexes involved in exocytosis.

In cell signaling

Its derivatives, for example, are second messengers in many hormone-related signaling processes in mammals.

Two of the most important secondary messengers that derive from what has been called "the hormone-sensitive phosphatidylinositol system" are inositol 1,4,5-triphosphate (IP3 or inositol triphosphate) and diacylglycerol, which fulfill various functions. down ”on the waterfall.

IP3 is involved in the hormone signaling cascade used by second messenger systems such as adrenaline.

Inositol is a soluble messenger that performs its functions in the cytosol, while diacylglycerol is fat-soluble and remains bound in the membrane, where it also functions as a messenger.

In the same way, in plants it has been determined that phosphorylated derivatives of phosphatidylinositol also have important functions in cell signaling cascades.

References

1. Antonsson, B. (1997). Phosphatidylinositol synthase from mammalian tissues. Biochimica et Biophysica Acta.
2. Luckey, M. (2008). Membrane structural biology: with biochemical and biophysical foundations. Cambridge University Press.
3. Murray, R., Bender, D., Botham, K., Kennelly, P., Rodwell, V., & Weil, P. (2009). Harper's Illustrated Biochemistry (28th ed.). McGraw-Hill Medical.
4. Nelson, DL, & Cox, MM (2009). Lehninger Principles of Biochemistry. Omega Editions (5th ed.).
5. Vance, JE, & Vance, DE (2008). Biochemistry of lipids, lipoproteins and membranes. In New Comprehensive Biochemistry Vol. 36 (4th ed.). Elsevier.