Filament Formation in Metabolic Enzymes
Summary
Metabolic enzymes have long been considered soluble catalysts operating independently in the cytosol or within defined organelles. Recent work, however, has revealed that many of these proteins can assemble into filamentous polymers or higher-order structures, fundamentally altering our understanding of metabolic regulation. Filament formation has been observed across phylogeny, from bacteria and yeast to mammalian cells, and involves enzymes central to nucleotide, amino-acid and energy metabolism. These dynamic assemblies often respond to nutrient status, stress or developmental cues, enabling switch-like control of enzymatic activity, sequestration of inactive pools and the creation of localised microenvironments for efficient substrate channeling. Structural studies indicate that polymerisation can impose conformational constraints that inhibit or enhance catalytic turnover, while mathematical models suggest that filamentation confers ultrasensitive response characteristics, buffering fluctuations in metabolite levels. Beyond basic cell physiology, filament formation has been implicated in gametogenesis, immune function and tumour progression, pointing to potential therapeutic strategies that target assembly interfaces or exploit filament dynamics to modulate enzyme activity in disease contexts.
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Filament Formation in Metabolic Enzymes publication trend
The graph below shows the total number of articles in filament formation in metabolic enzymes across all publications each year (not limited to Nature Index journals).
Technical terms
Filament: A linear polymeric assembly of protein subunits that can modulate enzyme function through conformational constraints.
Polymerisation: The process by which individual enzyme molecules associate into higher-order structures or filaments.
Cytoophidium: A specialised, often rod-like, intracellular filamentous compartment formed by nucleotide-synthesising enzymes.
Cryo-electron tomography: A high-resolution imaging technique that reconstructs three-dimensional structures of macromolecular assemblies in situ at cryogenic temperatures.
References
- FilamentID reveals the composition and function of metabolic enzyme polymers during gametogenesis. Cell (2024).
- Large-scale filament formation inhibits the activity of CTP synthetase. eLife (2014).
- Filamentation of Metabolic Enzymes in Saccharomyces cerevisiae. Journal of Genetics and Genomics (2016).
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