ArticlePLoS computational biology2020
ADP is the dominant controller of AMP-activated protein kinase activity dynamics in skeletal muscle during exercise.
Article in PLoS computational biology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers, 1 of them a synthesis that pooled it.
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Who cites it
16 citing papers in PubMed, 1 synthesis or guideline pooled it, 29 citations in OpenAlex.
- Factors Influencing AMPK Activation During Cycling Exercise: A Pooled Analysis and Meta-Regression.Sports medicine (Auckland, N.Z.) · 2022Pooled it
- Mechanochemical modeling of exercise-induced skeletal muscle hypertrophy.PLoS computational biology · 2026Article
- Systems modelling of mitochondrial dynamics in different exercise regimes.The Journal of physiology · 2026Article
- The oncogenic CCDC6-RET fusion protein is a dual ATP- and ADP-dependent kinase.Nature communications · 2026Article
- AMPK/mTOR balance during exercise: implications for insulin resistance in aging muscle.Molecular and cellular biochemistry · 2025Review
- Systems modeling and uncertainty quantification of AMP-activated protein kinase signaling.NPJ systems biology and applications · 2025Article
- AMPK in Intestinal Health and Disease: A Multifaceted Therapeutic Target for Metabolic and Inflammatory Disorders.Drug design, development and therapy · 2025Review
- Synergistic Effects of Omega-3 Fatty Acids and Physical Activity on Oxidative Stress Markers and Antioxidant Mechanisms in Aged Rats.Nutrients · 2024Article
- Short-term starvation activates AMPK and restores mitochondrial inorganic polyphosphate, but fails to reverse associated neuronal senescence.Aging cell · 2024Article
- Network model of skeletal muscle cell signalling predicts differential responses to endurance and resistance exercise training.Experimental physiology · 2024Article
- Review
- The Molecular Signature of High-intensity Training in the Human Body.International journal of sports medicine · 2022Review
- Sensing local energetics to acutely regulate mitophagy in skeletal muscle.Frontiers in cell and developmental biology · 2022Review
- Adenosine monophosphate activated protein kinase contributes to skeletal muscle health through the control of mitochondrial function.Frontiers in pharmacology · 2022Review
- Article
- Combination of Metformin and Exercise in Management of Metabolic Abnormalities Observed in Type 2 Diabetes Mellitus.Diabetes, metabolic syndrome and obesity : targets and therapy · 2021Review
Corrections and comments
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Exercise training elicits profound metabolic adaptations in skeletal muscle cells. A key molecule in coordinating these adaptations is AMP-activated protein kinase (AMPK), whose activity increases in response to cellular energy demand. AMPK activity dynamics are primarily controlled by the adenine nucleotides ADP and AMP, but how each contributes to its control in skeletal muscle during exercise is unclear. We developed and validated a mathematical model of AMPK signaling dynamics, and then applied global parameter sensitivity analyses with data-informed constraints to predict that AMPK activity dynamics are determined principally by ADP and not AMP. We then used the model to predict the effects of two additional direct-binding activators of AMPK, ZMP and Compound 991, further validating the model and demonstrating its applicability to understanding AMPK pharmacology. The relative effects of direct-binding activators can be understood in terms of four properties, namely their concentrations, binding affinities for AMPK, abilities to enhance AMPK phosphorylation, and the magnitudes of their allosteric activation of AMPK. Despite AMP's favorable values in three of these four properties, ADP is the dominant controller of AMPK activity dynamics in skeletal muscle during exercise by virtue of its higher concentration compared to that of AMP.
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