دورة كريبس (TCA أو CAC)

Study Notes

The Krebs cycle, also known as the Tricarboxylic Acid Cycle (TCA) or Citric Acid Cycle (CAC), is a series of chemical reactions that oxidizes acetyl-CoA to produce energy.
It's the final common pathway for the complete oxidation of carbohydrates, lipids, and proteins.
Coenzymes (NAD+ and FAD) are reduced during the cycle's reactions and then reoxidized by the respiratory chain, generating ATP.
The enzymes of the TCA cycle are located in the mitochondrial matrix, except for succinate dehydrogenase, which is bound to the inner mitochondrial membrane.
The cycle begins with the condensation of acetyl-CoA (2 carbons) and oxaloacetate (4 carbons) to form citrate (6 carbons).
The cycle proceeds through a series of reactions, eventually regenerating oxaloacetate and releasing two molecules of carbon dioxide per cycle.
One turn of the citric acid cycle produces 3 NADH, 1 FADH2, and 1 GTP (equivalent to 1 ATP), which are then used for ATP production through the electron transport chain.

Formation of Citrate: Acetyl-CoA combines with oxaloacetate to form citrate.
Formation of Isocitrate: Citrate is converted into isocitrate, a reversible reaction.
Formation of α-Ketoglutarate: Isocitrate is dehydrogenated and decarboxylated to α-ketoglutarate, releasing one CO2 and generating NADH.
Formation of Succinyl-CoA: α-ketoglutarate is oxidatively decarboxylated to succinyl-CoA, releasing another CO2 and generating NADH.
Formation of Succinate: Succinyl-CoA is converted to succinate, producing GTP (equivalent to ATP) in the process.
Formation of Fumarate: Succinate is dehydrogenated to fumarate, generating FADH2 in the process.
Formation of Malate: Fumarate is hydrated to malate.
Formation of Oxaloacetate: Malate is dehydrogenated to regenerate oxaloacetate, generating NADH.

Citrate: Exported to the cytosol and utilized in fatty acid and cholesterol synthesis.
α-ketoglutarate: A precursor to glutamate, an important amino acid.
Succinyl-CoA: Essential for heme synthesis.
Malate: Can be oxidized to oxaloacetate or decarboxylated to pyruvate, contributing to NADPH production.
Oxaloacetate: Transaminated to aspartate, crucial in amino acid metabolism and gluconeogenesis (formation of glucose).

Substrate Availability: The availability of both oxaloacetate and acetyl-CoA is important for citrate synthase activity.
Product Feedback Inhibition: Increased levels of succinyl-CoA can inhibit citrate synthase and α-ketoglutarate dehydrogenase.
ATP/ADP Ratio: High ATP/ADP ratio inhibits, while high ADP/ATP ratio activates the cycle.
NADH/NAD+ Ratio: High NADH/NAD+ ratio inhibits isocitrate dehydrogenase and α-ketoglutarate dehydrogenase.