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steps of the Krebs cycle citric acid cycle and ATP yield
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TL;DR
The retrieved papers only partially address this question. The evidence blocks discuss the tricarboxylic acid (TCA) cycle (also called the Krebs cycle or citric…
The retrieved papers only partially address this question. The evidence blocks discuss the tricarboxylic acid (TCA) cycle (also called the Krebs cycle or citric acid cycle) primarily in the context of specific metabolic conditions, organisms, and disease states, rather than providing a step-by-step textbook breakdown.12The TCA cycle is described as a central mitochondrial pathway that integrates catabolic conversions of NAD⁺ to NADH and anabolic production of key metabolites such as aspartate. Hart et al. (2023) The cycle is also characterized as a major metabolic hub involved in many disease states involving energetic imbalance.1
Chinopoulos (2013)
- TCA Cycle (Krebs/Citric Acid Cycle) — A central mitochondrial pathway integrating catabolic conversions of NAD⁺ to NADH and anabolic production of aspartate, a key amino acid for cell proliferation.
- α-Ketoglutarate Dehydrogenase Complex — A critical enzyme complex within the TCA cycle that dictates the directionality of cycle segments, particularly under hypoxic conditions when the electron transport chain is non-functional.
- Anaplerotic Pathways — Supplementary pathways (including enzymes such as citrate synthase, oxoglutarate dehydrogenase, pyruvate carboxylase, and malic enzymes) that maintain TCA cycle activity under specific conditions.
- TCA Cycle Metabolon — Protein complexes of sequential TCA enzymes that permit direct channelling of metabolites (such as citrate and fumarate) between enzymes, providing increased control over metabolic pathway fluxes.
1
Mitochondrial redox adaptations enable alternative aspartate synthesis in SDH-deficient cellsMadeleine L. Hart, Evan Quon et al.2023eLife
View 2
Which way does the citric acid cycle turn during hypoxia? The critical role of α‐ketoglutarate dehydrogenase complexChristos Chinopoulos2013Journal of Neuroscience Research
View 3
Tricarboxylic acid cycle and anaplerotic enzymes in rhizobiaMichael F. Dunn1998FEMS Microbiology Reviews
View 4
Protein-protein interactions and metabolite channelling in the plant tricarboxylic acid cycleYoujun Zhang, Katherine F. M. Beard et al.2017Nature Communications
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Diagram
Acetyl-CoA + Oxaloacetate | v [Citrate Synthase] --> Citrate | v Isocitrate | v [α-Ketoglutarate Dehydrogenase] --> α-Ketoglutarate --> Succinyl-CoA | v Succinate <-- [SDH / Complex II] | v Fumarate | v Malate | v Oxaloacetate (regenerated) | [NAD+ --> NADH at multiple steps] [Substrate-level phosphorylation: GTP/ATP] | v Electron Transport Chain --> Oxidative Phosphorylation --> ATP
(Diagram is a simplified representation based on retrieved evidence; exact step-by-step enzyme details are not fully covered in the retrieved papers.)
The TCA cycle operates differently depending on oxygen availability. Under hypoxia, when the electron transport chain cannot oxidize reducing equivalents, segments of the TCA cycle remain operational but exhibit opposing directionalities, serving to harness high-energy phosphates through matrix substrate-level phosphorylation in the absence of oxidative phosphorylation.1
Chinopoulos (2013)
1
Which way does the citric acid cycle turn during hypoxia? The critical role of α‐ketoglutarate dehydrogenase complexChristos Chinopoulos2013Journal of Neuroscience Research
View Regarding SDH (succinate dehydrogenase), also known as Complex II of the electron transport chain, loss-of-function mutations in its subunits are implicated in tumorigenesis. SDH supports human cell proliferation through aspartate synthesis, and its inhibition can be partially compensated by concomitant inhibition of ETC Complex I, which drives SDH-independent aspartate production through pyruvate carboxylation and reductive carboxylation of glutamine. Hart et al. (2023)
In rhizobia, a functional TCA cycle is essential for efficient colonization of plant hosts and effective nitrogen-fixing symbiosis, requiring a substantial input of energy from the rhizobial symbiont.2Dunn (1998)3
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- The retrieved papers do not provide a complete step-by-step enumeration of all TCA cycle reactions or a direct ATP yield calculation (e.g., net ATP per glucose). The evidence covers specific aspects such as hypoxic directionality and enzyme function rather than standard textbook ATP accounting. Chinopoulos (2013)
- The evidence on metabolon formation and metabolite channelling (citrate and fumarate) is described as fragmentary in vivo, meaning the full physiological significance of TCA metabolon organization remains incompletely established. Zhang et al. (2017)
- The TCA cycle is a major metabolic hub integrating energy production and biosynthesis, with NAD⁺ to NADH conversion being a central catabolic function.
- Under hypoxia, TCA cycle segments reverse direction to sustain substrate-level phosphorylation, with the α-ketoglutarate dehydrogenase complex playing a critical regulatory role.
- Anaplerotic enzymes such as pyruvate carboxylase and malic enzymes maintain TCA cycle activity under specific metabolic conditions. Dunn (1998)
- TCA cycle enzymes form protein complexes (metabolons) that channel metabolites like citrate and fumarate, suggesting tighter flux control than previously understood.
1
Which way does the citric acid cycle turn during hypoxia? The critical role of α‐ketoglutarate dehydrogenase complexChristos Chinopoulos2013Journal of Neuroscience Research
View 2
Tricarboxylic acid cycle and anaplerotic enzymes in rhizobiaMichael F. Dunn1998FEMS Microbiology Reviews
View 3
Protein-protein interactions and metabolite channelling in the plant tricarboxylic acid cycleYoujun Zhang, Katherine F. M. Beard et al.2017Nature Communications
View Want to research your own topic? Try it free →
- "Steps of the citric acid cycle enzymes substrates and products biochemistry textbook"
- "ATP yield per glucose oxidative phosphorylation NADH FADH2 stoichiometry"
- "Regulation of TCA cycle under normoxia vs hypoxia mitochondrial metabolism"
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