Citric acid cycle

Last revised by Frank Gaillard on 2 Oct 2023

Citation, DOI, disclosures and article data

Citation:

Gaillard F, Citric acid cycle. Reference article, Radiopaedia.org (Accessed on 30 Apr 2024) https://doi.org/10.53347/rID-176350

DOI:

https://doi.org/10.53347/rID-176350

Permalink:

https://radiopaedia.org/articles/176350

rID:

176350

Article created:

1 Oct 2023, Frank Gaillard ◉ ◈

Disclosures:

At the time the article was created Frank Gaillard had the following disclosures:

Biogen Australia Pty Ltd, Investigator-Initiated Research Grant for CAD software in multiple sclerosis: finished Oct 2021 (past)

These were assessed during peer review and were determined to not be relevant to the changes that were made.

View Frank Gaillard's current disclosures

Last revised:

2 Oct 2023, Frank Gaillard ◉ ◈

Disclosures:

At the time the article was last revised Frank Gaillard had the following disclosures:

Biogen Australia Pty Ltd, Investigator-Initiated Research Grant for CAD software in multiple sclerosis: finished Oct 2021 (past)

These were assessed during peer review and were determined to not be relevant to the changes that were made.

View Frank Gaillard's current disclosures

Revisions:

1 time, by 1 contributor - see full revision history and disclosures

Sections:

Pathology

Synonyms:

Tricarboxylic acid cycle
Krebs cycle
TCA cycle

The citric acid cycle, also known as the Krebs cycle or tricarboxylic acid cycle, is a central metabolic pathway in cells. It involves a series of chemical reactions that oxidize acetyl-CoA derived from carbohydrates, fats, and proteins to produce energy in the form of ATP and electron carriers (NADH and FADH2) and release carbon dioxide.

This cycle takes place within the mitochondria of eukaryotic cells and is a critical step in aerobic respiration.

The reason it is a cycle is that the series of metabolic steps is perpetual, recycling the end product (oxaloacetate) by combining it with acetyl-CoA to begin the cycle again.

Metabolic steps

acetyl-CoA entry: acetyl-CoA, derived from the breakdown of carbohydrates, fats, or proteins, enters the cycle and is combined with oxaloacetate to form citrate in a reaction catalyzed by the enzyme citrate synthase.
isomerization: citrate is converted to isocitrate by the enzyme aconitase.
first oxidation: isocitrate is oxidized to alpha-ketoglutarate with the production of NADH and the release of carbon dioxide (CO2). This reaction is catalyzed by isocitrate dehydrogenase.
second oxidation: alpha-ketoglutarate is further oxidized to succinyl-CoA, releasing NADH and CO2. This reaction is catalyzed by alpha-ketoglutarate dehydrogenase complex.
substrate-level phosphorylation: succinyl-CoA is converted to succinate, and in the process, a molecule of GTP is generated which in turn results in the phosphorylation of ADP into ATP the primary energy molecule of human metabolism. This step is catalyzed by succinyl-CoA synthetase.
third oxidation: succinate is oxidized to fumarate, producing FADH2, in a reaction catalyzed by succinate dehydrogenase, which is unique as it is embedded in the inner mitochondrial membrane and also participates in the electron transport chain.
hydration: fumarate is converted to malate via the addition of water. The enzyme responsible for this step is fumarase.
fourth oxidation: malate is oxidized to regenerate oxaloacetate, releasing NADH in the process. This reaction is catalyzed by malate dehydrogenase.