TCA cycle
Definition
The tricarboxylic acid (TCA) cycle, also known as the Krebs cycle or citric acid cycle, is a central metabolic pathway that oxidizes acetyl-CoA derived from carbohydrates, fats, and proteins to generate energy-rich molecules (NADH, FADH2) and precursors for biosynthesis. This eight-step cyclic pathway occurs in the mitochondrial matrix and produces CO2 as a byproduct while feeding electrons into the electron transport chain for ATP synthesis. The TCA cycle is critical for cellular energy homeostasis and serves as a metabolic hub connecting catabolic and anabolic processes. Dysregulation of TCA cycle enzymes and metabolites is implicated in cancer, neurodegenerative diseases, and metabolic disorders, making it a key focus in metabolomics research.
Visualize TCA cycle in Nodes Bio
Researchers can visualize TCA cycle metabolites and their interconnections with other metabolic pathways as network graphs in Nodes Bio. By mapping metabolite-enzyme relationships, substrate-product transformations, and regulatory feedback loops, users can identify metabolic bottlenecks, visualize flux distributions, and analyze how perturbations in one pathway component cascade through the network. Integration with gene expression or protein abundance data enables multi-omics network analysis.
Visualization Ideas:
- Metabolite-enzyme bipartite networks showing TCA cycle reactions and regulatory interactions
- Multi-omics integration networks connecting TCA metabolites with gene expression and protein abundance
- Pathway crosstalk networks illustrating TCA cycle connections to glycolysis, fatty acid oxidation, and amino acid metabolism
Example Use Case
A cancer metabolism researcher investigating Warburg effect mechanisms uses metabolomics to profile TCA cycle intermediates in tumor versus normal cells. They discover elevated succinate and fumarate levels, suggesting SDH and FH enzyme dysfunction. Using network visualization, they map how these oncometabolites connect to HIF-1α stabilization, epigenetic modifications, and altered gene expression networks. The integrated analysis reveals that succinate accumulation creates a metabolic vulnerability, identifying potential therapeutic targets for disrupting cancer cell energy metabolism through synthetic lethality approaches.