title: Inositol pyrophosphates: why so many phosphates?
abstract: The inositol pyrophosphates (PP-InsPs) are a specialized group of "energetic" signaling molecules found in yeasts, plants and animals. PP-InsPs boast the most crowded three dimensional phosphate arrays found in Nature; multiple phosphates and diphosphates are crammed around the six-carbon, inositol ring. Yet, phosphate esters are also a major energy currency in cells. So the synthesis of PP-InsPs, and the maintenance of their levels in the face of a high rate of ongoing turnover, all requires significant bioenergetic input. What are the particular properties of PP-InsPs that repay this investment of cellular energy? Potential answers to that question are discussed here, against the backdrop of a recent hypothesis that signaling by PP-InsPs is evolutionarily ancient. The latter idea is extended herein, with the proposal that the primordial origins of PP-InsPs is reflected in the apparent lack of isomeric specificity of certain of their actions. Nevertheless, there are other aspects of signaling by these polyphosphates that are more selective for a particular PP-InsP isomer. Consideration of the nature of both specific and non-specific effects of PP-InsPs can help rationalize why such molecules possess so many phosphates.
authors.affiliation: Inositol Signaling Group, Laboratory of Signal Transduction, National Institute of Environmental Health Sciences, NIH, DHHS, PO Box 12233, Research Triangle Park, NC 27709, USA. Electronic address: Shears@niehs.nih.gov.
authors.forename: Stephen B
authors.initials: SB
authors.lastname: Shears
mesh_terms: D000818:Animals; D004734:Energy Metabolism / Q000502:physiology*; D019143:Evolution, Molecular; D006801:Humans; D007295:Inositol Phosphates / Q000502:physiology*; D010944:Plants; D015398:Signal Transduction / Q000502:physiology*; D015003:Yeasts
chemical_list: D007295:Inositol Phosphates
keywords: Analogs; Cell-signaling; Diphosphoinositol polyphosphates; Inositol pyrophosphates; Kinase; Phosphorylation; Structure