ArticleNature communications2017
The self-inhibitory nature of metabolic networks and its alleviation through compartmentalization.
Article in Nature communications, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 58 papers.
What it found
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Who cites it
58 citing papers in PubMed, 134 citations in OpenAlex.
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- Not only an inhibitor: Trehalose enhances the catalytic action exerted on oxaloacetate by rabbit lactate dehydrogenase.Protein science : a publication of the Protein Society · 2025Article
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- Dynamic Transcription Machineries in Protocells.Journal of the American Chemical Society · 2025Review
- Systematic identification of allosteric effectors inProceedings of the National Academy of Sciences of the United States of America · 2025Article
- Carbon source diversity shapes bacterial interspecies interactions.The ISME journal · 2025Article
- Evolution of plant metabolism: the state-of-the-art.Philosophical transactions of the Royal Society of London. Series B, Biological sciences · 2024Review
- Organization of a functional glycolytic metabolon on mitochondria for metabolic efficiency.Nature metabolism · 2024Article
- Homeostatic coordination of cellular phosphate uptake and efflux requires an organelle-based receptor for the inositol pyrophosphate IP8.Cell reports · 2024Article
- DNA-empowered synthetic cells as minimalistic life forms.Nature reviews. Chemistry · 2024Review
- Metabolic exchanges are ubiquitous in natural microbial communities.Nature microbiology · 2023Review
- Mixed and non-competitive enzyme inhibition: underlying mechanisms and mechanistic irrelevance of the formal two-site model.Journal of enzyme inhibition and medicinal chemistry · 2023Review
- Membrane transporters in cell physiology, cancer metabolism and drug response.Disease models & mechanisms · 2023Review
- Peroxisomal compartmentalization of amino acid biosynthesis reactions imposes an upper limit on compartment size.Nature communications · 2023Article
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 4 countries.
Funding
Abstract
Metabolites can inhibit the enzymes that generate them. To explore the general nature of metabolic self-inhibition, we surveyed enzymological data accrued from a century of experimentation and generated a genome-scale enzyme-inhibition network. Enzyme inhibition is often driven by essential metabolites, affects the majority of biochemical processes, and is executed by a structured network whose topological organization is reflecting chemical similarities that exist between metabolites. Most inhibitory interactions are competitive, emerge in the close neighbourhood of the inhibited enzymes, and result from structural similarities between substrate and inhibitors. Structural constraints also explain one-third of allosteric inhibitors, a finding rationalized by crystallographic analysis of allosterically inhibited L-lactate dehydrogenase. Our findings suggest that the primary cause of metabolic enzyme inhibition is not the evolution of regulatory metabolite-enzyme interactions, but a finite structural diversity prevalent within the metabolome. In eukaryotes, compartmentalization minimizes inevitable enzyme inhibition and alleviates constraints that self-inhibition places on metabolism.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.