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Inositol pyrophosphates as multifaceted metabolites in the regulation of mammalian signaling networks
Authors:Seung Ju Park  Seulgi Lee  Seung Eun Park
Institution:Department of Biological Sciences, Korea Advanced Institute of Science and Technology (KAIST), Daejeon, Republic of Korea
Abstract:Inositol pyrophosphates (PP-IPs) such as 5-diphosphoinositol pentakisphosphate (5-IP7) are inositol metabolites with high-energy phosphoanhydride bonds. The formation of PP-IPs is catalyzed by two groups of enzymes, the IP6 kinases and the PPIP5 kinases, which both phosphorylate inositol hexakisphosphate (IP6). In mammals, PP-IPs are implicated in diverse biological phenomena including cellular growth, vesicular trafficking, apoptosis, and metabolic homeostasis. Mechanistically, all the diverse actions of PP-IPs proceed in one of two ways: the PP-IPs modulate the activity of their target proteins either through allosteric binding or protein pyrophosphorylation. In this review, we highlight recent advances in our understanding of the pleiotropic functions of the mammalian PP-IPs and the metabolic enzymes that produce them. We also discuss some future challenges in the exploration of areas where PP-IPs play important but unknown roles in physiology and disease.
Keywords:Metabolism  inositol pyrophosphate  IP6K  PPIP5K  cell signaling
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