Size-Specific Modulation of a Multienzyme Glucosome Assembly during the Cell Cycle
Miji Jeon1, Danielle L Schmitt1, Minjoung Kyoung1,2
1Department of Chemistry and Biochemistry, University of Maryland Baltimore County (UMBC); 1000 Hilltop Circle, Baltimore, Maryland 21250, United States.
Human cells regulate glucose metabolism via size-changing enzyme assemblies called glucosomes. Glucosome size modulation during the cell cycle impacts glucose flux, linking metabolism to cell progression.
Area of Science:
- Cell Biology
- Biochemistry
- Metabolic Regulation
Background:
- Enzymes in glucose metabolism are crucial for cell cycle progression.
- Measuring enzyme activity in living human cells during the cell cycle is challenging.
- Subcellular regulation of glucose metabolism to meet cell cycle demands remains unclear.
Purpose of the Study:
- To investigate the association between glucose metabolism and cell cycle progression in human cells.
- To explore how human cells regulate glucose metabolism at a subcellular level during the cell cycle.
- To characterize the role of multienzyme metabolic assemblies (glucosomes) in regulating glucose flux.
Main Methods:
- Cell synchronization and flow cytometry were used to monitor glucose metabolism.
- Enhanced green fluorescent protein-tagged phosphofructokinase served as an intracellular biomarker.
- Fluorescence single-cell imaging was employed to analyze glucosome size dynamics.
Main Results:
- Phosphofructokinase activity effectively tracks glucose metabolism state during the cell cycle.
- Glucosome size distribution significantly changes throughout the cell cycle in Hs578T cells.
- Medium-sized glucosomes are elevated in the G1 phase, while small-sized glucosomes show drastic changes.
Conclusions:
- Glucosome size modulation is a key mechanism regulating glucose flux between glycolysis and biosynthesis.
- Size-specific modulation of glucosomes links glucose metabolism to cell cycle progression.
- This provides insight into the metabolic significance of glucose metabolism in human cell biology.
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