The Inositol Phosphate System—A Coordinator of Metabolic Adaptability

Abstract

All cells rely on nutrients to supply energy and carbon building blocks to support cellular processes. Over time, eukaryotes have developed increasingly complex systems to integrate information about available nutrients with the internal state of energy stores to activate the necessary processes to meet the immediate and ongoing needs of the cell. One such system is the network of soluble and membrane-associated inositol phosphates that coordinate the cellular responses to nutrient uptake and utilization from growth factor signaling to energy homeostasis. In this review, we discuss the coordinated interactions of the inositol polyphosphates, inositol pyrophosphates, and phosphoinositides in major metabolic signaling pathways to illustrate the central importance of the inositol phosphate signaling network in nutrient responses.

Obesity and Overweight: Probing Causes, Consequences, and Novel Therapeutic Approaches Through the American Heart Association's Strategically Focused Research Network

“…Note that a full list of the articles supported through this center is included within the reference section. 15 , 16 , 17 , 18 , 19 , 20 , 21 , 22 , 23 , 24 , 25 Figure 2 summarizes the center's key accomplishments.…”

Pools of independently cycling inositol phosphates revealed by pulse labeling with18O-water

“…It will help us to create metabolic models of inositol phosphate-based signaling pathways and to better understand effects exerted by kinase inhibitors on cellular inositol phosphate fluxes, an area of growing interest in e.g. metabolic diseases (Tu-Sekine & Kim, 2022).…”

Expedient synthesis and luminescence sensing of the inositol pyrophosphate cellular messenger 5-PP-InsP5

“…Aer methanolysis, the product was dried thoroughly on a vacuum line. Phosphorylation of the deprotected 5-position phosphate was achieved using benzyl-protected phosphoramidite and 5-phenyl-1H-tetrazole to generate the mixed P(III)-P(V) anhydride that was subsequently oxidised using mCPBA to form the protected pyrophosphate (9). Importantly, an excess of 5-phenyl-1H-tetrazole was required during this phosphorylation to suppress competing cyclisation reactions.…”

“…8 5-PP-InsP 5 is thus a G-protein coupled receptor (GPCR) second messenger that is able to regulate synaptotagmin-7 (Syt7) dependent insulin release. 9 As a result of such emerging important functions as above, expedient synthetic routes to generate inositol pyrophosphates and analogues, 10 as well as tools to monitor their levels that could lead to the development of high throughput in vitro screening methods, are becoming more urgent and relevant. The ability to track the intracellular activity of 5-PP-InsP 5 quantitatively would be extremely useful for developing an accurate understanding of its cellular function.…”