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Biomolecules
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Inositol Phosphates in Health and Disease, 2nd Edition
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Inositol Phosphates in Health and Disease, 2nd Edition

A special issue of Biomolecules (ISSN 2218-273X). This special issue belongs to the section "Molecular Medicine".

Deadline for manuscript submissions: 30 June 2025 | Viewed by 12715

Special Issue Editors

Dr. Ivana Vucenik

E-Mail Website
Guest Editor
School of Medicine, University of Maryland, 100 Penn Street, Baltimore, MD 21201, USA
Interests: IP6; myo-inositol; other cyclitols: methods and determination; biological role; health-promoting activities; cancer; insulin resistance; pathological calcification
Special Issues, Collections and Topics in MDPI journals
Prof. Dr. Abulkalam M. Shamsuddin

E-Mail Website
Guest Editor
1. OncoVue, Inc. Columbia, MD, USA
2. IP-6 Research, Inc., Baltimore, MD, USA
3. Department of Natural Sciences, Coppin State University, Baltimore, MD, USA
Interests: carcinogenesis; markers of precancer and cancer; cancer screening tests; cancer prevention; regulation of cell growth and differentiation; inositol phosphates
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Inositol phosphates are a group of mono- to hexaphosphorylated inositols, including InsP1, InsP2, InsP3, InsP4, InsP5, InsP6, and inositol pyrophosphates. As a huge and complex family of biomolecules, inositol phosphates are important in regulating vital cellular functions, signal transduction, energy transmission, and ion channel physiology and serving as structural components of cell membranes.

Inositol phosphates are an important group of biomolecules present in eukaryotic cells. The most abundant member of this family in nature is InsP(6), usually known as phytate. As an important component of seeds, legumes, nuts, and whole grains, it has been proven to be beneficial to human health in a variety of diseases, including cancer, PCOS, metabolic diseases, pathological calcification, and neuropsychiatric diseases. Despite all the recent advances, many aspects of inositol phosphates are still not clear, so more research is needed.

This Special Issue of Biomolecules is dedicated to covering recent advances in our understanding and perspectives on inositol phosphates. Our aim is to compile a Special Issue describing recent advances in inositol phosphates in health and disease.

Dr. Ivana Vucenik
Prof. Dr. Abulkalam M. Shamsuddin
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Biomolecules is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2700 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • inositol polyphosphates (IPs)
  • IP6
  • inositol pyrophosphate (PP-Ips)
  • signal transduction
  • energy metabolism
  • anticancer activity
  • PCOS
  • metabolic diseases
  • pathological calcification
  • neuropsychiatric disease

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Related Special Issue

Published Papers (6 papers)

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Review

22 pages, 1950 KiB  
Review
Inositol and PIP2/PIP3 Ratio: At the Crossroad of the Biodynamic Interface Between Cells and Their Microenvironment
by Guglielmo Lentini, Alessandro Querqui, Alessandro Giuliani, Roberto Verna and Mariano Bizzarri
Biomolecules 2025, 15(3), 451; https://doi.org/10.3390/biom15030451 - 20 Mar 2025
Viewed by 422
Abstract
Plasma membrane plays a pivotal role in orchestrating motility and invasive processes, as well as mitosis and genome expression. Indeed, specialized regions of the plasma membrane enriched in phosphoinositides—namely PIP2 and PIP3—can accommodate the requirements of the dynamic interface, which mediates the interplay [...] Read more.
Plasma membrane plays a pivotal role in orchestrating motility and invasive processes, as well as mitosis and genome expression. Indeed, specialized regions of the plasma membrane enriched in phosphoinositides—namely PIP2 and PIP3—can accommodate the requirements of the dynamic interface, which mediates the interplay between cells and their microenvironment. The fine-tuned balance between the two phosphoinositides is instrumental in regulating cytoskeleton organization, motility, ion channel activation, and membrane traffic. The balanced expression of PIP2/PIP3 fulfills these functions by activating pathways through several transporter and receptor proteins. These dynamic interactions modulate the interplay with the extracellular environment by decreasing/increasing their exposure on the cell surface. In this way, lipid structures can rapidly either dismiss or recruit specific proteins, eventually favoring their cooperation with membrane receptors and ion channels. Particularly, exposure of proteins can be managed through the internalization of plasma membrane segments, while receptor signaling can be desensitized by their removal from the cell surface. Notably, the equilibrium between PIP2 and PIP3 is largely dependent on inositol availability, as inositol addition enhances PIP2 content while reducing PIP3 via PI3K inhibition. Pharmacological modulation of PIP2/PIP3 balance promises to be an interesting target in different clinical settings. Full article
(This article belongs to the Special Issue Inositol Phosphates in Health and Disease, 2nd Edition)
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14 pages, 1731 KiB  
Review
Inositol Phosphates and Synthesizing Enzymes: Implications in Neurodegenerative Disorders
by Chisom J. Onu, Michael Adu, Mohamed Chakkour, Vikalp Kumar and Miriam L. Greenberg
Biomolecules 2025, 15(2), 225; https://doi.org/10.3390/biom15020225 - 4 Feb 2025
Viewed by 1651
Abstract
Inositol is a vital sugar molecule involved in numerous signaling pathways required for cellular homeostasis and cell survival. Myo-inositol and its phospho-derivatives, inositol phosphates (IPs), are the most prevalent forms of inositol found in living cells. They are involved in regulating ion channels, [...] Read more.
Inositol is a vital sugar molecule involved in numerous signaling pathways required for cellular homeostasis and cell survival. Myo-inositol and its phospho-derivatives, inositol phosphates (IPs), are the most prevalent forms of inositol found in living cells. They are involved in regulating ion channels, metabolic flux, stress response, and other key biological processes. While emerging research has highlighted the significant roles of inositol phosphates in immunity, cancer, and metabolic diseases, there is a lack of comprehensive reviews on their roles in psychiatric and neurological disorders. This review aims to fill that gap by analyzing the existing literature on the importance of inositol phosphates in severe psychiatric and neurological conditions such as Parkinson’s disease, Alzheimer’s disease, bipolar disorder, amyotrophic lateral sclerosis, schizophrenia, and Huntington’s disease, underscoring the potential to pave the way for new treatment regimens for these debilitating disorders targeting inositol pathways. Full article
(This article belongs to the Special Issue Inositol Phosphates in Health and Disease, 2nd Edition)
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19 pages, 552 KiB  
Review
Inositol Hexaphosphate in Bone Health and Disease
by Yuji Yoshiko and Ivana Vucenik
Biomolecules 2024, 14(9), 1072; https://doi.org/10.3390/biom14091072 - 27 Aug 2024
Viewed by 2381
Abstract
Dietary phytic acid/phytate/myo-inositol hexaphosphate (IP6), a phosphate reservoir in plants, was viewed as antinutrient, caused by an influence on the bioavailability of minerals through its chelating activity. However, there is a growing body of evidence indicating that IP6 has beneficial (e.g., antiinflammatory, antibacterial, [...] Read more.
Dietary phytic acid/phytate/myo-inositol hexaphosphate (IP6), a phosphate reservoir in plants, was viewed as antinutrient, caused by an influence on the bioavailability of minerals through its chelating activity. However, there is a growing body of evidence indicating that IP6 has beneficial (e.g., antiinflammatory, antibacterial, and anticancer) effects on multiple biological processes. Also, IP6 and its metabolites are known to exist in mammalian cells, including human cells, and the role of IP6 as a functional molecule is attracting attention. IP6 can bind to the growth sites of hydroxy-apatite (HA) and calcium oxalate crystals to prevent their growth and hence inhibit pathological calcification. SNF472, hexasodium IP6, is currently being evaluated in clinical studies as a treatment for vascular calcification and calciphylaxis. However, since HA crystal growth within bone matrix is an essential process in bone formation, it is possible that IP6 intake may inhibit physiological mineralization and bone formation, although currently more published studies suggest that IP6 may contribute to bone health rather than inhibit bone formation. Given that IP6 and its metabolites are thought to have diverse activities and many health benefits, it remains important to consider the range of effects of IP6 on bone. Full article
(This article belongs to the Special Issue Inositol Phosphates in Health and Disease, 2nd Edition)
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15 pages, 2200 KiB  
Review
The Role of Inositols in Endocrine and Neuroendocrine Tumors
by Marilda Mormando, Giulia Puliani, Marta Bianchini, Rosa Lauretta and Marialuisa Appetecchia
Biomolecules 2024, 14(8), 1004; https://doi.org/10.3390/biom14081004 - 14 Aug 2024
Viewed by 1751
Abstract
Inositols have demonstrated a role in cancer prevention and treatment in many kinds of neoplasms. Their molecular mechanisms vary from the regulation of survival and proliferative pathways to the modulation of immunity and oxidative stress. The dysregulation of many pathways and mechanisms regulated [...] Read more.
Inositols have demonstrated a role in cancer prevention and treatment in many kinds of neoplasms. Their molecular mechanisms vary from the regulation of survival and proliferative pathways to the modulation of immunity and oxidative stress. The dysregulation of many pathways and mechanisms regulated by inositols has been demonstrated in endocrine and neuroendocrine tumors but the role of inositol supplementation in this context has not been clarified. The aim of this review is to summarize the molecular basis of the possible role of inositols in endocrine and neuroendocrine tumors, proposing it as an adjuvant therapy. Full article
(This article belongs to the Special Issue Inositol Phosphates in Health and Disease, 2nd Edition)
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17 pages, 1473 KiB  
Review
Kcs1 and Vip1: The Key Enzymes behind Inositol Pyrophosphate Signaling in Saccharomyces cerevisiae
by Larisa Ioana Gogianu, Lavinia Liliana Ruta and Ileana Cornelia Farcasanu
Biomolecules 2024, 14(2), 152; https://doi.org/10.3390/biom14020152 - 26 Jan 2024
Cited by 2 | Viewed by 2563
Abstract
The inositol pyrophosphate pathway, a complex cell signaling network, plays a pivotal role in orchestrating vital cellular processes in the budding yeast, where it regulates cell cycle progression, growth, endocytosis, exocytosis, apoptosis, telomere elongation, ribosome biogenesis, and stress responses. This pathway has gained [...] Read more.
The inositol pyrophosphate pathway, a complex cell signaling network, plays a pivotal role in orchestrating vital cellular processes in the budding yeast, where it regulates cell cycle progression, growth, endocytosis, exocytosis, apoptosis, telomere elongation, ribosome biogenesis, and stress responses. This pathway has gained significant attention in pharmacology and medicine due to its role in generating inositol pyrophosphates, which serve as crucial signaling molecules not only in yeast, but also in higher eukaryotes. As targets for therapeutic development, genetic modifications within this pathway hold promise for disease treatment strategies, offering practical applications in biotechnology. The model organism Saccharomyces cerevisiae, renowned for its genetic tractability, has been instrumental in various studies related to the inositol pyrophosphate pathway. This review is focused on the Kcs1 and Vip1, the two enzymes involved in the biosynthesis of inositol pyrophosphate in S. cerevisiae, highlighting their roles in various cell processes, and providing an up-to-date overview of their relationship with phosphate homeostasis. Moreover, the review underscores the potential applications of these findings in the realms of medicine and biotechnology, highlighting the profound implications of comprehending this intricate signaling network. Full article
(This article belongs to the Special Issue Inositol Phosphates in Health and Disease, 2nd Edition)
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19 pages, 3096 KiB  
Review
The Role of Inositol Hexakisphosphate Kinase in the Central Nervous System
by Tyler Heitmann and James C. Barrow
Biomolecules 2023, 13(9), 1317; https://doi.org/10.3390/biom13091317 - 28 Aug 2023
Cited by 5 | Viewed by 2802
Abstract
Inositol is a unique biological small molecule that can be phosphorylated or even further pyrophosphorylated on each of its six hydroxyl groups. These numerous phosphorylation states of inositol along with the kinases and phosphatases that interconvert them comprise the inositol phosphate signaling pathway. [...] Read more.
Inositol is a unique biological small molecule that can be phosphorylated or even further pyrophosphorylated on each of its six hydroxyl groups. These numerous phosphorylation states of inositol along with the kinases and phosphatases that interconvert them comprise the inositol phosphate signaling pathway. Inositol hexakisphosphate kinases, or IP6Ks, convert the fully mono-phosphorylated inositol to the pyrophosphate 5-IP7 (also denoted IP7). There are three isoforms of IP6K: IP6K1, 2, and 3. Decades of work have established a central role for IP6Ks in cell signaling. Genetic and pharmacologic manipulation of IP6Ks in vivo and in vitro has shown their importance in metabolic disease, chronic kidney disease, insulin signaling, phosphate homeostasis, and numerous other cellular and physiologic processes. In addition to these peripheral processes, a growing body of literature has shown the role of IP6Ks in the central nervous system (CNS). IP6Ks have a key role in synaptic vesicle regulation, Akt/GSK3 signaling, neuronal migration, cell death, autophagy, nuclear translocation, and phosphate homeostasis. IP6Ks’ regulation of these cellular processes has functional implications in vivo in behavior and CNS anatomy. Full article
(This article belongs to the Special Issue Inositol Phosphates in Health and Disease, 2nd Edition)
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