Inositol phosphate

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Inositol Inositol structure.png
Inositol
Phosphate group Phosphate Group.svg
Phosphate group

Inositol phosphates are a group of mono- to hexaphosphorylated inositols. Each form of inositol phosphate is distinguished by the number and position of the phosphate group on the inositol ring.

Contents

A series of phosphorylation and dephosphorylation reactions are carried out by at least 19 phosphoinositide kinases and 28 phosphoinositide phosphatase enzymes [1] allowing for the inter-conversion between the inositol phosphate compounds based on cellular demand.

Inositol phosphates play a crucial role in various signal transduction pathways responsible for cell growth and differentiation, apoptosis, DNA repair, RNA export, regeneration of ATP and more.

Functions

Inositol trisphosphate

inositol-phospholipid signaling pathway IP3 veikimas.png
inositol-phospholipid signaling pathway

The inositol-phospholipid signaling pathway is responsible for the generation of IP3 through the cleavage of Phosphatidylinositol 4,5-bisphosphate (PIP2) found in the lipid bi-layer of the plasma membrane by phospholipase C in response to either receptor tyrosine kinase or Gq alpha subunit-G protein-coupled receptor signaling. Soluble inositol trisphosphate (IP3) is able to rapidly diffuse into the cytosol and bind to the inositol trisphosphate receptor (InsP3Rs) calcium channels located in the endoplasmic reticulum. This releases calcium into the cytosol, serving as a rapid and potent signal for various cellular processes. [1]

Further reading: Function of calcium in humans

Other

Inositol tetra-, penta-, and hexa-phosphates have been implicated in gene expression. [2] [3]

Inositol hexaphosphate

Inositol hexaphosphate (IP6) is the most abundant inositol phosphate isomer found. IP6 is solely involved in various biological activities such as neurotransmission, immune response, regulation of kinase and phosphatase proteins as well as activation of calcium channels. [1] IP6 is also involved in ATP regeneration seen in plants as well as insulin exocytosis in pancreatic β cells.

Inositol hexaphosphate also facilitates the formation of the six-helix bundle and assembly of the immature HIV-1 Gag lattice. IP6 makes ionic contacts with two rings of lysine residues at the centre of the Gag hexamer. Proteolytic cleavage then unmasks an alternative binding site, where IP6 interaction promotes the assembly of the mature capsid lattice. These studies identify IP6 as a naturally occurring small molecule that promotes both assembly and maturation of HIV-1. [4]

Related Research Articles

Inositol trisphosphate or inositol 1,4,5-trisphosphate abbreviated InsP3 or Ins3P or IP3 is an inositol phosphate signaling molecule. It is made by hydrolysis of phosphatidylinositol 4,5-bisphosphate (PIP2), a phospholipid that is located in the plasma membrane, by phospholipase C (PLC). Together with diacylglycerol (DAG), IP3 is a second messenger molecule used in signal transduction in biological cells. While DAG stays inside the membrane, IP3 is soluble and diffuses through the cell, where it binds to its receptor, which is a calcium channel located in the endoplasmic reticulum. When IP3 binds its receptor, calcium is released into the cytosol, thereby activating various calcium regulated intracellular signals.

<span class="mw-page-title-main">Inositol</span> Carbocyclic sugar

Inositol, primarily the isomer myo-inositol, is a carbocyclic sugar that is abundant in the brain and other mammalian tissues; it mediates cell signal transduction in response to a variety of hormones, neurotransmitters, and growth factors and participates in osmoregulation. Concerning regulation of osmosis, in most mammalian cells the intracellular concentrations of myo-inositol are 5 to 500 times greater than the extracellular concentrations.

<span class="mw-page-title-main">Phosphatidylinositol</span> Signaling molecule

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.

<span class="mw-page-title-main">Phytic acid</span> Chemical compound

Phytic acid is a six-fold dihydrogenphosphate ester of inositol, also called inositol hexaphosphate, inositol hexakisphosphate (IP6) or inositol polyphosphate. At physiological pH, the phosphates are partially ionized, resulting in the phytate anion.

Second messengers are intracellular signaling molecules released by the cell in response to exposure to extracellular signaling molecules—the first messengers. Second messengers trigger physiological changes at cellular level such as proliferation, differentiation, migration, survival, apoptosis and depolarization.

<span class="mw-page-title-main">Phosphoinositide phospholipase C</span>

Phosphoinositide phospholipase C is a family of eukaryotic intracellular enzymes that play an important role in signal transduction processes. These enzymes belong to a larger superfamily of Phospholipase C. Other families of phospholipase C enzymes have been identified in bacteria and trypanosomes. Phospholipases C are phosphodiesterases.

<span class="mw-page-title-main">Phosphatidylinositol (3,4,5)-trisphosphate</span> Chemical compound

Phosphatidylinositol (3,4,5)-trisphosphate (PtdIns(3,4,5)P3), abbreviated PIP3, is the product of the class I phosphoinositide 3-kinases' (PI 3-kinases) phosphorylation of phosphatidylinositol (4,5)-bisphosphate (PIP2). It is a phospholipid that resides on the plasma membrane.

<span class="mw-page-title-main">Phosphatidylinositol 4,5-bisphosphate</span> Chemical compound

Phosphatidylinositol 4,5-bisphosphate or PtdIns(4,5)P2, also known simply as PIP2 or PI(4,5)P2, is a minor phospholipid component of cell membranes. PtdIns(4,5)P2 is enriched at the plasma membrane where it is a substrate for a number of important signaling proteins. PIP2 also forms lipid clusters that sort proteins.

<span class="mw-page-title-main">Phosphatidylinositol 3,4-bisphosphate</span>

Phosphatidylinositol (3,4)-bisphosphate is a minor phospholipid component of cell membranes, yet an important second messenger. The generation of PtdIns(3,4)P2 at the plasma membrane activates a number of important cell signaling pathways.

<span class="mw-page-title-main">ITPKB</span> Protein-coding gene in the species Homo sapiens

Inositol-trisphosphate 3-kinase B is an enzyme that in humans is encoded by the ITPKB gene.

The enzyme inositol-1,4-bisphosphate 1-phosphatase (EC 3.1.3.57) catalyzes the reaction

<span class="mw-page-title-main">Inositol-phosphate phosphatase</span> Class of enzymes

The enzyme Inositol phosphate-phosphatase is of the phosphodiesterase family of enzymes. It is involved in the phosphophatidylinositol signaling pathway, which affects a wide array of cell functions, including but not limited to, cell growth, apoptosis, secretion, and information processing. Inhibition of inositol monophosphatase may be key in the action of lithium in treating bipolar disorder, specifically manic depression.

The enzyme phosphoinositide 5-phosphatase (EC 3.1.3.36) catalyzes the reaction

<span class="mw-page-title-main">Inositol-trisphosphate 3-kinase</span> Class of enzymes

Inositol (1,4,5) trisphosphate 3-kinase (EC 2.7.1.127), abbreviated here as ITP3K, is an enzyme that facilitates a phospho-group transfer from adenosine triphosphate to 1D-myo-inositol 1,4,5-trisphosphate. This enzyme belongs to the family of transferases, specifically those transferring phosphorus-containing groups (phosphotransferases) with an alcohol group as acceptor. The systematic name of this enzyme class is ATP:1D-myo-inositol-1,4,5-trisphosphate 3-phosphotransferase. ITP3K catalyzes the transfer of the gamma-phosphate from ATP to the 3-position of inositol 1,4,5-trisphosphate to form inositol 1,3,4,5-tetrakisphosphate. ITP3K is highly specific for the 1,4,5-isomer of IP3, and it exclusively phosphorylates the 3-OH position, producing Ins(1,3,4,5)P4, also known as inositol tetrakisphosphate or IP4.

In enzymology, a phosphatidylinositol-4,5-bisphosphate 3-kinase is an enzyme that catalyzes the chemical reaction:

<span class="mw-page-title-main">INPP5D</span> Protein-coding gene in the species Homo sapiens

Src homology 2 (SH2) domain containing inositol polyphosphate 5-phosphatase 1(SHIP1) is an enzyme with phosphatase activity. SHIP1 is structured by multiple domain and is encoded by the INPP5D gene in humans. SHIP1 is expressed predominantly by hematopoietic cells but also, for example, by osteoblasts and endothelial cells. This phosphatase is important for the regulation of cellular activation. Not only catalytic but also adaptor activities of this protein are involved in this process. Its movement from the cytosol to the cytoplasmic membrane, where predominantly performs its function, is mediated by tyrosine phosphorylation of the intracellular chains of cell surface receptors that SHIP1 binds. Insufficient regulation of SHIP1 leads to different pathologies.

<span class="mw-page-title-main">Phospholipase C</span> Class of enzymes

Phospholipase C (PLC) is a class of membrane-associated enzymes that cleave phospholipids just before the phosphate group (see figure). It is most commonly taken to be synonymous with the human forms of this enzyme, which play an important role in eukaryotic cell physiology, in particular signal transduction pathways. Phospholipase C's role in signal transduction is its cleavage of phosphatidylinositol 4,5-bisphosphate (PIP2) into diacyl glycerol (DAG) and inositol 1,4,5-trisphosphate (IP3), which serve as second messengers. Activators of each PLC vary, but typically include heterotrimeric G protein subunits, protein tyrosine kinases, small G proteins, Ca2+, and phospholipids.

<span class="mw-page-title-main">INPP4A</span> Protein-coding gene in the species Homo sapiens

Type I inositol-3,4-bisphosphate 4-phosphatase is an enzyme that in humans is encoded by the INPP4A gene.

The enzyme Inositol-polyphosphate 5-phosphatase (EC 3.1.3.56, systematic name 1D-myo-inositol-1,4,5-trisphosphate 5-phosphohydrolase; other names type I inositol-polyphosphate phosphatase, inositol trisphosphate phosphomonoesterase, InsP3/Ins(1,3,4,5)P4 5-phosphatase, inosine triphosphatase, D-myo-inositol 1,4,5-triphosphate 5-phosphatase, D-myo-inositol 1,4,5-trisphosphate 5-phosphatase, L-myo-inositol 1,4,5-trisphosphate-monoesterase, inositol phosphate 5-phosphomonoesterase, inositol-1,4,5-trisphosphate/1,3,4,5-tetrakisphosphate 5-phosphatase, Ins(1,4,5)P3 5-phosphataseD-myo-inositol(1,4,5)/(1,3,4,5)-polyphosphate 5-phosphatase, inositol 1,4,5-trisphosphate phosphatase, inositol polyphosphate-5-phosphatase, myo-inositol-1,4,5-trisphosphate 5-phosphatase, inositol-1,4,5-trisphosphate 5-phosphatase) catalyses the following reaction

<span class="mw-page-title-main">Inositol polyphosphate kinase</span> Enzyme family

Inositol polyphosphate kinase (IPK) is a family of enzymes that have a similar 3-dimensional structure. All members of the family catalyze the transfer of phosphate groups from ATP to various inositol phosphates. Members of the family include inositol-polyphosphate multikinases, inositol-hexakisphosphate kinases, inositol-trisphosphate 3-kinases, and inositol-pentakisphosphate 2-kinase, which is more distantly related to the others

References

  1. 1 2 3 Shamsuddin AK, Yang GY (2015-03-04). "Safety of Inositol and Inositol Phosphates". In Shamsuddin A, Yang GY (eds.). Inositol & its Phosphates: Basic Science to Practical Applications. Bentham Science Publishers. pp. 275–282. doi:10.2174/9781681080079115010024. ISBN   9781681080079.
  2. Shen X, Xiao H, Ranallo R, Wu WH, Wu C (January 2003). "Modulation of ATP-dependent chromatin-remodeling complexes by inositol polyphosphates". Science. 299 (5603): 112–114. doi: 10.1126/science.1078068 . PMID   12434013. S2CID   8381889.
  3. Steger DJ, Haswell ES, Miller AL, Wente SR, O'Shea EK (January 2003). "Regulation of chromatin remodeling by inositol polyphosphates". Science. 299 (5603): 114–116. doi:10.1126/science.1078062. PMC   1458531 . PMID   12434012.
  4. Dick RA, Zadrozny KK, Xu C, Schur FK, Lyddon TD, Ricana CL, et al. (August 2018). "Inositol phosphates are assembly co-factors for HIV-1". Nature. 560 (7719): 509–512. Bibcode:2018Natur.560..509D. doi:10.1038/s41586-018-0396-4. PMC   6242333 . PMID   30069050.