Inositol phosphate explained

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.

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

See main article: Inositol trisphosphate. 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.

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. 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]

References

  1. Book: Safety of Inositol and Inositol Phosphates . 2015-03-04 . 10.2174/9781681080079115010024 . Inositol & its Phosphates: Basic Science to Practical Applications . 275–282 . Shamsuddin AK, Yang GY . A.K.M. . Guang-Yu . Shamsuddin . Yang . Bentham Science Publishers . 9781681080079 .
  2. Shen X, Xiao H, Ranallo R, Wu WH, Wu C . Modulation of ATP-dependent chromatin-remodeling complexes by inositol polyphosphates . Science . 299 . 5603 . 112–114 . January 2003 . 12434013 . 10.1126/science.1078068 . 8381889 . free .
  3. Steger DJ, Haswell ES, Miller AL, Wente SR, O'Shea EK . Regulation of chromatin remodeling by inositol polyphosphates . Science . 299 . 5603 . 114–116 . January 2003 . 12434012 . 1458531 . 10.1126/science.1078062 .
  4. Dick RA, Zadrozny KK, Xu C, Schur FK, Lyddon TD, Ricana CL, Wagner JM, Perilla JR, Ganser-Pornillos BK, Johnson MC, Pornillos O, Vogt VM . 6 . Inositol phosphates are assembly co-factors for HIV-1 . Nature . 560 . 7719 . 509–512 . August 2018 . 30069050 . 6242333 . 10.1038/s41586-018-0396-4 . 2018Natur.560..509D .