Glutamine metabolic enzymes: to filament or not to filament?

The self-assembly of metabolic enzymes into filaments and other supramolecular structures is well-documented in bacteria and yeast but remains largely unexplored in mammalian cells. Enzyme filamentation is thought to play a crucial role in regulating metabolic networks by modulating enzymatic activity in response to cellular demands. Studies in yeast suggest that filament-forming enzymes are often positioned at key junctions of metabolic pathways, enabling dynamic activation or inactivation during growth or stress and directing metabolic flux accordingly. While this mechanism appears to be broadly conserved across species, the structural and functional characterization of human homologs of filamentous enzymes remains limited. In the present review, we focus on the glutamine metabolic pathway, highlighting enzymes known to form large self-assemblies in cells and examining the few cases where structural insights are available. Finally, we discuss the broader implications of metabolic enzyme filamentation in mammalian cells, underscoring its potential as an emerging area of research.