The citric acid cycle, also known as the Krebs cycle, is a crucial metabolic pathway that processes acetyl CoA to generate energy. When one molecule of acetyl CoA enters the cycle, it produces three molecules of NADH, one molecule of FADH2, and one molecule of GTP (or ATP). This means that if glucose is the starting point, which yields two acetyl CoA molecules through glycolysis, the total output from one glucose molecule would be doubled. Additionally, the cycle releases two molecules of carbon dioxide, which are byproducts of the process.
The cycle begins with the combination of acetyl CoA and oxaloacetate, a four-carbon molecule, to form citrate. The carbon atoms from acetyl CoA can be tracked through the cycle, with the oxaloacetate carbons represented differently to distinguish their origins. The first significant reaction occurs when isocitrate is converted to alpha-ketoglutarate, resulting in the release of the first carbon dioxide and the generation of NADH. The next key step involves the conversion of alpha-ketoglutarate to succinyl CoA, which also releases a carbon dioxide molecule and produces another NADH.
In the subsequent reaction, succinyl CoA is transformed into succinate, during which GTP is produced through substrate-level phosphorylation. This GTP can be converted to ATP in some cells, highlighting the interchangeable nature of these nucleotide triphosphates in terms of energy currency. The cycle continues with the conversion of succinate to fumarate, generating the only FADH2 produced in the cycle. Following this, fumarate is converted to malate, which is then oxidized back to oxaloacetate, producing the final NADH.
Throughout the cycle, it is important to note that steps 1, 3, and 4 are the primary drivers of the process due to their negative Gibbs free energy (ΔG), which ensures the cycle proceeds in a forward direction. In contrast, steps 5, 6, 7, and 8, along with step 2, have ΔG values close to zero, allowing for reversibility. This dynamic nature of the cycle is essential for maintaining metabolic balance.
In terms of carbon tracking, if labeled carbon atoms are introduced into the cycle, only half of the labeled carbons will be released as carbon dioxide in the first turn, with subsequent turns releasing progressively fewer labeled carbons. This illustrates the randomization of succinate's orientation during its conversion, emphasizing the complexity of the cycle's reactions.
Overall, the citric acid cycle is a vital component of cellular respiration, linking carbohydrate metabolism to energy production through the generation of high-energy electron carriers and nucleotide triphosphates.
