About the TCA Cycle Efficiency Calculator
The TCA Cycle Efficiency Calculator is a scientifically validated, web-based metabolic modeling tool that quantifies the efficiency of the tricarboxylic acid (TCA) cycle, also known as the Krebs cycle or citric acid cycle. Discovered by Hans Krebs in 1937 and awarded the Nobel Prize in 1953, the TCA cycle is the central hub of cellular respiration, oxidizing acetyl-CoA to CO₂ while generating NADH, FADH₂, and GTP for oxidative phosphorylation. The TCA Cycle Efficiency Calculator implements the exact stoichiometry and bioenergetic principles from peer-reviewed biochemical literature.
By integrating anaplerotic and cataplerotic fluxes, this calculator provides comprehensive analysis of carbon balance, ATP yield, and respiratory quotient—essential for metabolic flux analysis (MFA), cancer metabolism, and mitochondrial disease research.
TCA Cycle Stoichiometry and Reactions
Per turn of the cycle (1 acetyl-CoA):
- 3 NADH → 7.5 ATP (P/O = 2.5)
- 1 FADH₂ → 1.5 ATP (P/O = 1.5)
- 1 GTP → 1 ATP (substrate-level)
- 2 CO₂ released
- Total: ~10 ATP
Key Enzymes:
- Citrate synthase
- Isocitrate dehydrogenase (NADH)
- α-Ketoglutarate dehydrogenase (NADH + CO₂)
- Succinate dehydrogenase (FADH₂)
- Succinyl-CoA synthetase (GTP)
Importance of TCA Cycle Efficiency
The TCA cycle is the oxidative powerhouse of the cell:
- 90% of cellular ATP from TCA + OXPHOS
- Links carbohydrate, fat, protein catabolism
- Biosynthetic precursor for amino acids, nucleotides, lipids
- Regulates redox balance via NADH/NAD⁺ ratio
When and Why You Should Use This Calculator
Use the TCA Cycle Efficiency Calculator when:
- Performing ¹³C metabolic flux analysis (MFA)
- Modeling cancer cell metabolism (Warburg effect)
- Studying mitochondrial disorders (PDH deficiency, fumarase mutations)
- Teaching central carbon metabolism
- Optimizing microbial fermentation yields
Clinical Relevance:
- Oncometabolites: 2-HG, fumarate, succinate
- Diabetes: impaired PDH-TCA coupling
- Neurodegeneration: α-KG dysregulation
- Aging: declining TCA flux
User Guidelines for Accurate Results
To ensure precision:
- Input acetyl-CoA from PDH or β-oxidation
- Include anaplerosis for glutamine, propionate
- Balance cataplerosis for biosynthesis
- Use standard P/O ratios (2.5/1.5) or measured values
- Validate with glucose:
- 1 glucose → 2 acetyl-CoA → ~20 ATP from TCA
- Total cellular: ~30–32 ATP
Purpose and Research Applications
This calculator enables:
- Quantitative MFA integration
- Drug target identification in TCA enzymes
- Biotech strain engineering
- Personalized medicine via metabolomics
Interpretation of Results
Key outputs include:
- ATP yield: Total from OXPHOS + substrate-level
- Redox carriers: NADH, FADH₂ for ETC
- Carbon efficiency: % of input C oxidized to CO₂
- RQ: CO₂ produced / O₂ consumed
Limitations and Advanced Considerations
Model assumptions:
- Steady-state flux
- No reverse flux (e.g., reductive carboxylation)
- Standard P/O ratios
- Neglects compartmentation
References and Further Reading
- Krebs HA, Johnson WA. (1937). The role of citric acid in intermediate metabolism. Enzymologia.
- Hinkle PC. (2005). P/O ratios of mitochondrial oxidative phosphorylation. Biochim Biophys Acta.
- Owen OE, et al. (2002). The key role of anaplerosis and cataplerosis. J Clin Invest.
- DeBerardinis RJ, et al. (2008). The biology of cancer: metabolic reprogramming. Cell Metab.
- Fernie AR, et al. (2004). Respiratory metabolism: glycolysis, the TCA cycle and mitochondrial electron transport. Curr Opin Plant Biol.
For agricultural applications of plant metabolism, visit Agri Care Hub. Learn more about the central pathway on the TCA Cycle Efficiency Calculator Wikipedia page.