# Novel Mechanisms of Regulation of Inositol Biosynthesis

> **NIH NIH R01** · WAYNE STATE UNIVERSITY · 2020 · $333,874

## Abstract

PROJECT SUMMARY
 Inositol is a ubiquitous six-carbon cyclitol that is essential for viability of eukaryotic cells.
Inositol compounds play pivotal roles in cell signaling and metabolism, and regulate virtually
every aspect of cellular physiology. Consistent with its importance, perturbation of inositol
metabolism is associated with pathologies as diverse as neurological and psychiatric illnesses,
myopathies, cancer, and diabetes. In this light, it is striking that almost nothing is known about
how inositol synthesis is regulated in mammalian cells. The goal of the proposed research is
to elucidate the molecular mechanisms that regulate inositol synthesis. To this end, we
have exploited yeast genetics to identify novel mechanisms of regulation of inositol synthesis,
and mammalian cells to test hypotheses generated by the yeast studies. Using this approach,
we identified three novel mechanisms of regulation of inositol synthesis, which are the focus of
this proposal. Aim 1 will elucidate the mechanism whereby phosphorylation regulates myo-
inositol-3-phosphate synthase (MIPS), which catalyzes the rate-limiting step in inositol de novo
synthesis. Aim 2 will test our hypothesis that MIPS is regulated by metabolic channeling of the
common intermediate, glucose-6-phosphate, and that down-regulation of inositol synthesis is
triggered by increased demand for glycolysis. Aim 3 will determine the physiological
significance of transcriptional control of mammalian INO1 expression by inositol pyrophosphate
synthase (IP6K1). We expect these studies to generate the first molecular model of regulation of
inositol synthesis in mammalian cells. The model will suggest a new paradigm with which to
understand how cross talk between glycolysis and inositol synthesis regulates these essential
metabolic pathways. The outcome of these studies will contribute to our understanding of
essential cellular processes that require inositol, and open the door to the development of new
therapeutics for the treatment of bipolar disorder, epilepsy, and other illnesses in which inositol
homeostasis is perturbed.

## Key facts

- **NIH application ID:** 9993540
- **Project number:** 5R01GM125082-08
- **Recipient organization:** WAYNE STATE UNIVERSITY
- **Principal Investigator:** Miriam L Greenberg
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $333,874
- **Award type:** 5
- **Project period:** 2009-05-01 → 2022-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9993540

## Citation

> US National Institutes of Health, RePORTER application 9993540, Novel Mechanisms of Regulation of Inositol Biosynthesis (5R01GM125082-08). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9993540. Licensed CC0.

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