ArticleProceedings of the National Academy of Sciences of the United States of America2024
Brain energy metabolism is optimized to minimize the cost of enzyme synthesis and transport.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.
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Who cites it
8 citing papers in PubMed, 11 citations in OpenAlex.
- A scoping review of computational models on human glucose cerebral metabolism.Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism · 2026Review
- Frequency-specific photobiomodulation at theta and gamma enhances cognitive networks and mitigates age-related decline.GeroScience · 2026Article
- From energy metabolism to mood regulation: The rise of lactate as a therapeutic target.Journal of advanced research · 2026Review
- Direct energy consumption by inhibitory GABAFrontiers in neuroscience · 2026Article
- Neurovascular Signaling at the Gliovascular Interface: From Flow Regulation to Cognitive Energy Coupling.International journal of molecular sciences · 2025Review
- The Energetic Collapse of the Alzheimer's Brain: Metabolic Inflexibility Across Cells and Networks.Journal of neurochemistry · 2025Review
- Brain energy metabolism is optimized to minimize the cost of enzyme synthesis and transport.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Resource allocation in mammalian systems.Biotechnology advancesReview
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Authors and funding
4 authors at 3 institutions in 4 countries.
Funding
Abstract
The energy metabolism of the brain is poorly understood partly due to the complex morphology of neurons and fluctuations in ATP demand over time. To investigate this, we used metabolic models that estimate enzyme usage per pathway, enzyme utilization over time, and enzyme transportation to evaluate how these parameters and processes affect ATP costs for enzyme synthesis and transportation. Our models show that the total enzyme maintenance energy expenditure of the human body depends on how glycolysis and mitochondrial respiration are distributed both across and within cell types in the brain. We suggest that brain metabolism is optimized to minimize the ATP maintenance cost by distributing the different ATP generation pathways in an advantageous way across cell types and potentially also across synapses within the same cell. Our models support this hypothesis by predicting export of lactate from both neurons and astrocytes during peak ATP demand, reproducing results from experimental measurements reported in the literature. Furthermore, our models provide potential explanation for parts of the astrocyte-neuron lactate shuttle theory, which is recapitulated under some conditions in the brain, while contradicting other aspects of the theory. We conclude that enzyme usage per pathway, enzyme utilization over time, and enzyme transportation are important factors for defining the optimal distribution of ATP production pathways, opening a broad avenue to explore in brain metabolism.
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