The Tricarboxylic acid cycle, also called the Krebs cycle or the citric acid cycle, is the final pathway where oxidative metabolism of carbohydrates, amino acids, and fatty acids converge. Carbon skeletons are converted into carbon dioxide and water, producing energy for the production of the majority of ATP.
The TCA cycle occurs in the mitochondria in close proximity to the electron trnasport chain.
The TCA cycle may be viewed as a traffic circle, with components entering and leaving at various points as required.
Puruvate, the final product of aerobic glycolysis, is transported into the mitochondrion matrix by a specific transporter and irreversibly converted into acetyl CoA by a multi-enzyme complex.
Five coenzymes are required for this process: thiamine pyrophosphate, lipoic acid, coenzyme A, FAD, and NAD+. Arsenic poisoning inhibits enzymes requiring lipoic acid as a cofactor.
Acetyl CoA enters the TCA cycle and combines with oxaloacetate to form citrate, which provides negative feedback to glycolysis by inhibiting PFK-1.
The sequence of reactions then goes: citrate, isocitrate,α-ketoglutarate, succinyl CoA, succinate, fumarate, malate, oxaloacetate, and finally back to citrate.
A,C,I,K,SC,S,F,M,O
Two carbon atoms enter the TCA cycle as Acetyl CoA and leave as CO2. During one turn of this cycle, three pairs of electrons reduce NAD+ to NADH, one pair reduces FAD to FADH2, and one GTP is produced. NADH and FADH2 then go on to the electron transport chain, where they are used to generate ATP. Oxidation of one NADH results in two ATP, while one FADH2 yields two ATP.
| Reaction | # of ATP |
|---|---|
| 3 NADH | 9 |
| FADH2 | 2 |
| GTP | 1 |
| Net: | 12 |
Various components of the TCA cycle can be used as substrates for other metabolic pathways.
Pyruvate can also enter the TCA cycle through conversion by puruvate carboxylase to oxaloacetate, providing more carbon to the system if it is actively being used to synthesize proteins or lipids.
