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Updated: Feb 8, 2026
Author Spotlight: Characterizing Novel Enzymes from Extremophiles and Common Pathogens to Understand DNA Repair and Replication
Published on: July 5, 2024
Hidden features: exploring the non-canonical functions of metabolic enzymes
Peiwei Huangyang1,2, M Celeste Simon3,4
1Abramson Family Cancer Research Institute, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
Abstract:
The study of cellular metabolism has been rigorously revisited over the past decade, especially in the field of cancer research, revealing new insights that expand our understanding of malignancy. Among these insights is the discovery that various metabolic enzymes have surprising activities outside of their established metabolic roles, including in the regulation of gene expression, DNA damage repair, cell cycle progression and apoptosis. Many of these newly identified functions are activated in response to growth factor signaling, nutrient and oxygen availability, and external stress. As such, multifaceted enzymes directly link metabolism to gene transcription and diverse physiological and pathological processes to maintain cell homeostasis. In this Review, we summarize the current understanding of non-canonical functions of multifaceted metabolic enzymes in disease settings, especially cancer, and discuss specific circumstances in which they are employed. We also highlight the important role of subcellular localization in activating these novel functions. Understanding their non-canonical properties should enhance the development of new therapeutic strategies for cancer treatment.
Insights
Metabolic enzymes have surprising roles beyond metabolism, influencing gene expression and cell processes. Understanding these non-canonical functions, especially in cancer, can lead to new treatments.
Area of Science:
- Biochemistry
- Molecular Biology
- Cancer Research
Background:
- Cellular metabolism research has advanced significantly, particularly in cancer.
- Metabolic enzymes are now known to possess functions beyond their metabolic roles.
- These non-canonical functions are often linked to cellular signaling and stress responses.
Purpose of the Study:
- To review the non-canonical functions of metabolic enzymes in disease, focusing on cancer.
- To discuss the circumstances activating these novel enzyme activities.
- To highlight the role of subcellular localization in these functions.
Main Methods:
- Literature review of recent studies on metabolic enzymes.
- Analysis of non-canonical enzyme activities in various disease contexts.
- Examination of the link between enzyme localization and function.
Main Results:
- Metabolic enzymes regulate gene expression, DNA repair, cell cycle, and apoptosis.
- These functions are activated by growth factors, nutrients, oxygen, and stress.
- Subcellular localization is critical for activating these non-canonical roles.
Conclusions:
- Multifaceted metabolic enzymes bridge metabolism with gene transcription and cellular homeostasis.
- Understanding non-canonical functions is crucial for developing novel cancer therapeutics.
- Targeting these enzymes offers potential for new cancer treatment strategies.
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