A central metabolic pathway where acetyl-CoA is oxidized to generate energy in the form of ATP, NADH, and FADH2 through a series of chemical reactions occurring in the mitochondrial matrix.

Citric Acid Cycle

Also known as the Krebs cycle or tricarboxylic acid cycle, the citric acid cycle represents a fundamental hub of cellular metabolism that occurs within the mitochondria of eukaryotic cells.

Core Process

The cycle begins when acetyl-CoA (derived from the glycolysis of glucose and other nutrients) combines with oxaloacetate to form citrate, the molecule that gives the cycle its name. Through a series of eight distinct steps, this citrate molecule undergoes sequential transformations, ultimately regenerating oxaloacetate while producing:

2 molecules of CO2 (decarboxylation)
6 NADH molecules
2 FADH2 molecules
2 ATP (or GTP) molecules

Key Enzymes and Reactions

The cycle employs several crucial enzymes:

Citrate synthase - Catalyzes the initial condensation reaction
Aconitase - Converts citrate to isocitrate
α-Ketoglutarate dehydrogenase complex - Performs a key decarboxylation step
Succinate dehydrogenase - Links the cycle to the electron transport chain

Regulatory Mechanisms

The citric acid cycle is tightly regulated through several metabolic regulation:

ATP availability
NAD+/NADH ratio
Substrate availability
allosteric regulation effects
hormone signaling influences

Clinical Significance

Dysfunction in the citric acid cycle can lead to various metabolic disorders, including:

Integration with Other Pathways

The cycle serves as a metabolic hub, connecting to:

This central position makes the citric acid cycle essential for both catabolism and anabolism processes.

Evolution and Conservation

The citric acid cycle represents one of the most evolutionary conservation metabolic pathways, appearing in organisms from bacteria to humans, highlighting its fundamental importance in cellular energetics and metabolism.

Research Applications

Understanding the citric acid cycle has led to developments in:

The cycle's centrality in metabolism makes it a continued focus of biochemical research and metabolomics studies.