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Phosphatidylinositol or inositol phospholipid is a biomolecule. It was initially called "inosite" when it was discovered by Léon Maquenne and Johann Joseph von Scherer in the late 19th century. It was discovered in bacteria but later also found in eukaryotes, and was found to be a signaling molecule.
The biomolecule can exist in 9 different isomers. It is a lipid which contains a phosphate group, two fatty acid chains, and one inositol sugar molecule. Typically, the phosphate group has a negative charge (at physiological pH values). As a result, the molecule is amphiphilic.
The production of the molecule is limited to the endoplasmic reticulum.
The esterified presence of inositol in lipids, particularly PI, was first observed in bacteria and later confirmed in eukaryotic organisms by researchers like Clinton Ballou and Dan Brown. Their pioneering work established the structure of PI and its phosphorylated forms, shedding light on their roles as signaling molecules. Despite the complexity of inositol nomenclature and isomerism, modern research has greatly advanced the understanding of their diverse functions in cellular physiology and signaling pathways.
The discovery of PI and its derivatives, along with their intricate roles in cellular signaling, marks a significant chapter in the field of biochemistry. From early investigations into inositol's structure to the identification of its various isomers and their physiological functions, the study of inositol compounds continues to uncover new insights into cellular processes.
PI can exist in nine different forms, myo-, scyllo-, muco-, epi-, neo-, allo-, D-chiro-, L-chiro-, and cis-inositol. These Isomer are common in biology and have many functions, for example taste sensory, regulating phosphate levels, metabolic flux, transcription, mRNA export and translation, insulin signaling, embryonic development and stress response. Cis-inositol is the only isomer not found naturally in nature.
PI exhibits an Amphiphile nature, with both polar and non-polar regions, due to its glycerophospholipid structure containing a glycerol backbone, two non-polar fatty acid tails, and a phosphate group substituted with an inositol polar head group.
All seven variations of the following phosphoinositides have been found in animals:
Phosphatidylinositol monophosphates:
Phosphatidylinositol bisphosphates:
Phosphatidylinositol trisphosphate:
These phosphoinositides are also found in plant cells, with the exception of PIP3.
The biosynthesis and phosphorylation of PI is mainly confined to the Cytosol facing surface of organelles by already residential Kinase, but not at the ER specifically. De novo PI synthesis of PI starts with an Acylation process of Glyceraldehyde-3-phosphate (G-3-P) by GPAT enzymes at the sn-1 acyl chain position. The process is then followed by a second acylation with LPAAT1, LPAAT2 and LPAAT3, LPAAT enzymes, at the sn-2 acyl chain position. This double step process acylates G-3-P to phosphatidic acid (PA).
PA is converted into the intermediate CDP-diacylglycerol (CDP-DAG) by an enzyme called CDP-diacylglycerol synthase. Two genes, CDS1 and CDS2, encode different isoforms of CDP-diacylglycerol synthase. In the final enzymatic process, CDP-DAG and inositol are used as substrates by the enzyme CDIPT and converted into PI and cytidine monophosphate (CMP).
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