8.5: The Citric Acid Cycle
The citric acid cycle is a closed loop of reactions that occur in the mitochondrial matrix, including redox, dehydration, hydration, and decarboxylation reactions. Its name is derived from the intermediate compound, citric acid. As the steps were first identified by Hans Krebs, this aerobic pathway is also known as the Krebs cycle, which over a series of eight enzymatic steps, is critical in glucose catabolism.
To begin, acetyl Co-A, the resulting compound from pyruvate oxidation, donates its acetyl group to four-carbon molecule oxaloacetate, forming a six-carbon intermediate, citrate, while its co-A group is bound to a sulfhydryl group and diffused away to eventually combine with another acetyl group. A water molecule is then removed and replaced, transforming citrate into its isomer, isocitrate. This molecule is then oxidized––reducing NAD+ to NADH and H+––and a carbon dioxide molecule, forming a five-carbon alpha-ketoglutarate. This product loses another carbon dioxide molecule and is oxidized, releasing two electrons again––reducing another NAD+ to NADH and H+–– leaving the molecule with an unstable bond, where a Coenzyme A attaches.
The resulting product of step four, now a four-carbon molecule, succinyl CoA, loses the coenzyme which is replaced by a phosphate group, then the molecule is phosphorylated, forming succinate and GTP, which can be used to generate ATP, depending on the type of tissue. During step six, succinate is oxidized, with two electrons from hydrogen atoms transferred to the electron carrier flavine adenine dinucleotide, FAD, to produce FADH2 and fumarate.
Water is then added to the resulting molecule, and after bond rearrangement, forms into malate. Finally, this molecule is oxidized, reducing NAD+ to NADH and H+, regenerating the original compound, oxaloacetate. In the end, each cycle produces three NADH and one FADH2 molecules––high-energy electron carriers that are used in the electron transport chain.