Inositol phosphate

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.

Inositol
Phosphate group

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 can either be soluble or insoluble depending on their chemical structure. Insoluble inositol phosphates are often referred to as phosphoinositides or PtdInsP and can be found associated with sub-cellular membranes or in nuclear subdomains. PIP2 (also known as PtdIns(4,5)P2) is found to be hydrophobic in nature and thus remains attached to the plasma membrane in the cell. Soluble inositol phosphates such as IP3 (Ins(1,4,5)P3) are able to dissolve in the cytoplasm of cells contributing to its crucial role as a secondary messenger in signal transduction pathways.[2]

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 triphosphate
Main article: Inositol triphosphate
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 via G proteins (Gq) and phospholipase C-β. Soluble IP3 is able to rapidly diffuse into the cytosol and bind to the inositol triphosphate receptor (InsP3Rs) located in the endoplasmic reticulum. High concentrations of calcium will be released from the endoplasmic reticulum as a result, serving as a rapid and potent signal for various cellular processes. Here, IP3 is functioning as a secondary messenger responsible for activating the InsP3Rs which serve as a connection point for multiple signal transduction pathways.[1]

Further reading: Function of calcium in humans

Other

Inositol tetra-, penta-, and hexa-phosphates have been implicated in gene expression.[3][4]

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.[5]

References
  1. Shamsuddin AK, Yang GY (2015-03-04). "Safety of Inositol and Inositol Phosphates". In Shamsuddin A, Yang G (eds.). Inositol & its Phosphates: Basic Science to Practical Applications. Bentham Science Publishers. pp. 275–282. doi:10.2174/9781681080079115010024. ISBN 9781681080079.
  2. Tu-Sekine B, Kim SF (June 2022). "The Inositol Phosphate System-A Coordinator of Metabolic Adaptability". International Journal of Molecular Sciences. 23 (12): 6747. doi:10.3390/ijms23126747. PMC 9223660. PMID 35743190.
  3. 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.
  4. 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.
  5. 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.
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