ArticleJournal of the Royal Society, Interface2021
Metabolic buffer analysis reveals the simultaneous, independent control of ATP and adenylate energy ratios.
Article in Journal of the Royal Society, Interface, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.
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Who cites it
4 citing papers in PubMed, 7 citations in OpenAlex.
- Loss of adenylosuccinate synthetase 1 in mice recapitulates features of ADSS1 myopathy.Human molecular genetics · 2026Article
- The first report of AMP-deaminase activity in skeletal muscles of Lates calcarifer and its stunning adaptation to ammonia poisoning.Fish physiology and biochemistry · 2025Article
- What can ATP content tell us about Barth syndrome muscle phenotypes?Journal of translational genetics and genomics · 2025Article
- Stabilization of antithetic control via molecular buffering.Journal of the Royal Society, Interface · 2022Article
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Authors and funding
3 authors at 2 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Determining the underlying principles behind biological regulation is important for understanding the principles of life, treating complex diseases and creating de novo synthetic biology. Buffering-the use of reservoirs of molecules to maintain molecular concentrations-is a widespread and important mechanism for biological regulation. However, a lack of theory has limited our understanding of its roles and quantified effects. Here, we study buffering in energy metabolism using control theory and novel buffer analysis. We find that buffering can enable the simultaneous, independent control of multiple coupled outputs. In metabolism, adenylate kinase and AMP deaminase enable simultaneous control of ATP and adenylate energy ratios, while feedback on metabolic pathways is fundamentally limited to controlling one of these outputs. We also quantify the regulatory effects of the phosphagen system-the above buffers and creatine kinase-revealing which mechanisms regulate which outputs. The results are supported by human muscle and mouse adipocyte data. Together, these results illustrate the synergy of feedback and buffering in molecular biology to simultaneously control multiple outputs.
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