Related Experiment Video
Updated: Oct 3, 2026

Measurement of Insulin- and Contraction-Stimulated Glucose Uptake in Isolated and Incubated Mature Skeletal Muscle from Mice
Published on: May 16, 2021
Control of glycolysis in contracting skeletal muscle. II. Turning it off
Gregory J Crowther1, William F Kemper, Michael F Carey
1Department of Physiology and Biophysics, University of Washington Medical Center, Seattle, Washington 98195-7115, USA.
Abstract:
Glycolytic flux in muscle declines rapidly after exercise stops, indicating that muscle activation is a key controller of glycolysis. The mechanism underlying this control could be 1) a Ca(2+)-mediated modulation of glycogenolysis, which supplies substrate (hexose phosphates, HP) to the glycolytic pathway, or 2) a direct effect on glycolytic enzymes. To distinguish between these possibilities, HP levels were raised by voluntary 1-Hz exercise, and glycolytic flux was measured after the exercise ceased. Glycolytic H(+) and ATP production were quantified from changes in muscle pH, phosphocreatine concentration, and P(i) concentration as measured by 31P magnetic resonance spectroscopy. Substrate (HP) and metabolite (P(i), ADP, and AMP) levels remained high when exercise stopped because of the occlusion of blood flow with a pressure cuff. Glycolytic flux declined to basal levels within approximately 20 s of the end of exercise despite elevated levels of HP and metabolites. Therefore, this flux does not subside because of insufficient HP substrate; rather, glycolysis is controlled independently of glycogenolytic HP production. We conclude that the inactivation of glycolysis after exercise reflects the cessation of contractile activity and is mediated within the glycolytic pathway rather than via the control of glycogen breakdown.
Insights
Muscle activation controls glycolysis, not substrate availability. After exercise, glycolytic flux rapidly declines despite high substrate levels, indicating direct regulation within the glycolytic pathway itself.
Area of Science:
- Exercise Physiology
- Muscle Metabolism
- Biochemistry
Background:
- Muscle activation is a key regulator of glycolysis.
- The precise mechanism of this control remains unclear, with possibilities including calcium-mediated glycogenolysis or direct enzyme modulation.
Purpose of the Study:
- To distinguish between substrate availability and direct enzymatic control of muscle glycolysis after exercise cessation.
- To investigate the role of glycogenolysis in supplying substrate (hexose phosphates) to glycolysis post-exercise.
Main Methods:
- Voluntary 1-Hz exercise was used to elevate hexose phosphate (HP) levels in muscle.
- Muscle pH, phosphocreatine, and inorganic phosphate (Pi) were measured using 31P magnetic resonance spectroscopy to quantify glycolytic flux, H+, and ATP production.
- Blood flow occlusion was employed to maintain elevated substrate and metabolite levels after exercise.
Main Results:
- Glycolytic flux rapidly declined to basal levels within 20 seconds after exercise ceased.
- Elevated levels of hexose phosphates (HP) and key metabolites (Pi, ADP, AMP) persisted post-exercise due to blood flow occlusion.
- The decline in glycolytic flux occurred independently of substrate (HP) availability.
Conclusions:
- Muscle glycolysis is primarily controlled by factors within the glycolytic pathway, not by the rate of glycogen breakdown.
- The cessation of contractile activity directly mediates the inactivation of glycolysis post-exercise.
- Glycolysis regulation is independent of glycogenolytic substrate production.
Related Concept Videos
What is Glycolysis?
Cells make energy by breaking down macromolecules. Cellular respiration is the biochemical process that converts "food energy" (from the chemical bonds of macromolecules) into chemical energy in the form of adenosine triphosphate (ATP). The first step of this tightly regulated and intricate process is glycolysis. The word glycolysis originates from the Latin glyco (sugar) and lysis (breakdown). Glycolysis serves two main intracellular functions: generating ATP and generating...
Energy Supply for Muscle Contraction
Muscle Recovery and Fatigue
Cross-bridge Cycle
Other Glycolytic Pathways
Outcomes of Glycolysis
Cellular respiration can occur aerobically (with oxygen) or anaerobically (without oxygen). In the presence of oxygen, cellular respiration starts with glycolysis and continues with pyruvate oxidation, the...

