# Elucidating the mechanism behind oscillation between glycolysis and gluconeogenesis

> **NIH NIH R35** · UNIVERSITY OF CALIFORNIA LOS ANGELES · 2022 · $370,415

## Abstract

Project Summary
The overarching research goal of the Park lab is to gain systems-level understanding of
metabolism (including its regulation) and rationally engineer mammalian and microbial
metabolism for biotechnology and medicine. We are a team of open-minded and hardworking
researchers who employ core analytical techniques and ceaselessly innovate (and adopt) new
technologies to solve challenging problems associated with various diseases and organisms.
Our current research is twofold: microbial conversion of carbon dioxide into value-add products
for economic and environmental benefits; and elucidation of thermodynamic and kinetic mode of
metabolic control in mammalian gluconeogenesis. One of our goals over the next five years is to
develop key technologies to mathematically reconstruct human central carbon metabolism in
thermodynamic and kinetic terms. Until recently, characterization of metabolism has relied
mainly on comparison of relative metabolite and enzyme levels between control and
experimental groups. We will go beyond measuring just the “levels” and quantify rates and
energies, which are direct representation of metabolism in action yet difficult to measure
because they are substantive yet intangible. To this end, we will employ state-of-the-art liquid
chromatography-mass spectrometry, mathematical modeling, and novel isotope tracers that can
yield the most thermodynamic and kinetic information in cellular metabolism. We aim to apply
these techniques to investigating the two central metabolic pathways: glycolysis and
gluconeogenesis. The two pathways largely share a common enzyme set, yet the former
converts glucose into cellular energy and biomass precursors while the latter converts non-
carbohydrate substrates into glucose. These functionally opposite metabolic pathways support
systemic glucose homeostasis in humans and, in microbes, various bioproduct synthesis from a
wide range of carbon substrates with varying degrees of oxidation. This project will map kinetic
and thermodynamic bottlenecks of the two pathways in mammalian cells and elucidate
regulatory mechanisms that enable seamless transitions and coordination between them. As
dysregulation of these pathways are implicated in type II diabetes and cancer, we envision that
this research program will lead to effective metabolic control and engineering strategies to
remedy defective carbon metabolism in diseases. The upshot of successfully completing the
proposed research will contribute to advancing therapeutic development for diabetes and
cancer.

## Key facts

- **NIH application ID:** 10436979
- **Project number:** 5R35GM143127-02
- **Recipient organization:** UNIVERSITY OF CALIFORNIA LOS ANGELES
- **Principal Investigator:** Junyoung O. Park
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $370,415
- **Award type:** 5
- **Project period:** 2021-07-01 → 2026-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10436979

## Citation

> US National Institutes of Health, RePORTER application 10436979, Elucidating the mechanism behind oscillation between glycolysis and gluconeogenesis (5R35GM143127-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10436979. Licensed CC0.

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