Phosphatidylinositol

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Phosphatidylinositol

Depicting the Phosphatidylinisitol molecule with an overview of different segregated components; Inositol, Phosphate, Glycerol-backbone, sn-1 acyl chain, sn-2 acyl chain. Made by Mathias Sollie Sandsdalen in BioRender.com, modified from N.J. Blunsom and S. Cockcroft.[1]
Names
IUPAC name [(2R)-3-[hydroxy-[(5R)-2,3,4,5,6-pentahydroxycyclohexyl]oxyphosphoryl]oxy-2-octadecanoyloxypropyl] (8Z,11Z,14Z,17Z)-icosa-8,11,14,17-tetraenoate
Other names PI PtdIns
Identifiers
ChEBI	CHEBI:28874
DrugBank	DB02144
Properties
Chemical formula	C47H83O13P
Molar mass	887,104 g/mol, neutral with fatty acid composition - 18:0, 20:4
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa). Y verify (what is YN ?) Infobox references

Phosphatidylinositol or inositol phospholipid is a

The biomolecule can exist in 9 different isomers. It is a

The production of the molecule is limited to the endoplasmic reticulum.

History of phospatidylinositol

Phosphatidylinositol (PI) and its derivatives have a rich history dating back to their discovery by Johann Joseph von Scherer

The esterified presence of

The discovery of PI and its derivatives, along with their intricate roles in cellular signaling, marks a significant chapter in the field of

Phosphatidylinositol (PI), also known as inositol phospholipid, is a lipid composed of a phosphate group, two fatty acid chains, and one inositol molecule. It belongs to the class of phosphatidylglycerides and is typically found as a minor component on the cytosolic side of eukaryotic cell membranes. The phosphate group imparts a negative charge to the molecules at physiological pH.^[13]

PI can exist in nine different forms, myo-, scyllo-, muco-, epi-, neo-, allo-, D-chiro-, L-chiro-, and cis-inositol. These isomers 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.^[14]

PI exhibits an amphiphilic 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.^[15]

Phosphoinositides

Phosphorylated forms of phosphatidylinositol (PI) are called phosphoinositides and play important roles in

• Phosphatidylinositol 3-phosphate, also known as PtdIns3P or PI(3)P
• Phosphatidylinositol 4-phosphate, also known as PtdIns4P or PI(4)P
• Phosphatidylinositol 5-phosphate, also known as PtdIns5P or PI(5)P

Phosphatidylinositol bisphosphates:

• Phosphatidylinositol 3,4-bisphosphate, also known as PtdIns(3,4)P₂ or PI(3,4)P₂
• Phosphatidylinositol 3,5-bisphosphate, also known as PtdIns(3,5)P₂ or PI(3,5)P₂
• Phosphatidylinositol 4,5-bisphosphate, also known as PtdIns(4,5)P₂, PI(4,5)P₂ or often simply referred to as PIP₂

Phosphatidylinositol trisphosphate:

• Phosphatidylinositol 3,4,5-trisphosphate
  , also known as PtdIns(3,4,5)P₃ or PI(3,4,5)P₃

These phosphoinositides are also found in plant cells, with the exception of PIP₃.^[17][18][19]

Hydrolysis

The significance of phosphatidylinositol (PI) metabolism lies in its role as a potential transducing mechanism, evident from studies showing hormone and neurotransmitter-induced hydrolysis of PI. The hydrolysis starts with the enzyme PI 4-kinase alpha (PI4Kα) converting PI into PI 4-phosphate (PI4P), which is then converted into PI (4,5) biphosphate (PI(4,5)P₂) by the enzyme PI 4-phosphate-5-kinase (PI4P5K). PI(4,5)P₂ is then hydrolysed by phospholipase C (PLC) and forms the second messengers, inositol (1,4,5) triphosphate (IP₃) and diacylglycerol (DG). DG is then phosphyrylated to phosphatidic acid (PA) by DG kinase (DGK). PA is also directly produced from phosphatidylcholine (PC) by phospholipase D (PLD). Lipid transfer proteins facilitate the exchange of PI and PA between membranes, ensuring its availability for receptor mechanisms on the plasma membrane, even in organelles like mitochondria incapable of PI synthesis.^[20][21][22]

Biosynthesis

The synthesis of Phosphatidylinositol (PI) is limited to the Endoplasmatic Reticulum (ER), which is the largest membrane componement of the cell.^[23] This site also contributes the synthesis to the majority of phospholipids, namely phosphatidylcholine (PC), phosphatidylethanolamine (PE), phosphatidylserine (PS) and triacylglycerol (TG).^[24] The synthesis involves a series of enzymatic reactions.

The biosynthesis and phosphorylation of PI is mainly confined to the cytosolic facing surface of organelles by already residential kinases, but not at the ER spesifically. De novo PI synthesis of PI starts with an acylated process of Glyceraldehyde-3-phosphate (G-3-P) by GPAT enzymes at the sn-1 acyl chain position.^[25] The process is then followed by a second acylation with LPAAT1, LPAAT2 and LPAAT3, LPAAT enzymes, at the sn-2 acyl chain position.^[26] This double step process acylates G-3-P to phosphatidic acid (PA).

PA is converted into the intermediate CDP- diacylglycerol (CDP-DG) by a process called CDP-diaglycerol synthase. This synthesis is catalyzed by the use of CDS1 and CDS2, CDS- enzymes. In the final enzymatic process, CDP-DG and inositol are catalyzed by the enzyme PI synthase (PIS) and synthesised into PI.^[27][28]

References