OpenStax Anatomy and Physiology
The pyruvate molecules generated during glycolysis are transported across the mitochondrial membrane into the inner mitochondrial matrix, where they are metabolized by enzymes in a pathway called the Krebs cycle. The Krebs cycle is also commonly called the citric acid cycle or the tricarboxylic acid (TCA) cycle. During the Krebs cycle, high-energy molecules, including ATP, NADH, and FADH2, are created. NADH and FADH2 then pass electrons through the electron transport chain in the mitochondria to generate more ATP molecules.
The three-carbon pyruvate molecule generated during glycolysis moves from the cytoplasm into the mitochondrial matrix, where it is converted by the enzyme pyruvate dehydrogenase into a two-carbon acetyl coenzyme A (acetyl CoA) molecule. This reaction is an oxidative decarboxylation reaction. It converts the three-carbon pyruvate into a two-carbon acetyl CoA molecule, releasing carbon dioxide and transferring two electrons that combine with NAD+ to form NADH. Acetyl CoA enters the Krebs cycle by combining with a four-carbon molecule, oxaloacetate, to form the six-carbon molecule citrate, or citric acid, at the same time releasing the coenzyme A molecule.
The six-carbon citrate molecule is systematically converted to a five-carbon molecule and then a four-carbon molecule, ending with oxaloacetate, the beginning of the cycle. Along the way, each citrate molecule will produce one ATP, one FADH2, and three NADH. The FADH2 and NADH will enter the oxidative phosphorylation system located in the inner mitochondrial membrane. In addition, the Krebs cycle supplies the starting materials to process and break down proteins and fats.
To start the Krebs cycle, citrate synthase combines acetyl CoA and oxaloacetate to form a six-carbon citrate molecule; CoA is subsequently released and can combine with another pyruvate molecule to begin the cycle again. The aconitase enzyme converts citrate into isocitrate. In two successive steps of oxidative decarboxylation, two molecules of CO2 and two NADH molecules are produced when isocitrate dehydrogenase converts isocitrate into the five-carbon α-ketoglutarate, which is then catalyzed and converted into the four-carbon succinyl CoA by α-ketoglutarate dehydrogenase. The enzyme succinyl CoA dehydrogenase then converts succinyl CoA into succinate and forms the high-energy molecule GTP, which transfers its energy to ADP to produce ATP. Succinate dehydrogenase then converts succinate into fumarate, forming a molecule of FADH2. Fumarase then converts fumarate into malate, which malate dehydrogenase then converts back into oxaloacetate while reducing NAD+ to NADH. Oxaloacetate is then ready to combine with the next acetyl CoA to start the Krebs cycle again. For each turn of the cycle, three NADH, one ATP (through GTP), and one FADH2 are created. Each carbon of pyruvate is converted into CO2, which is released as a byproduct of oxidative (aerobic) respiration.
Betts, J. G., Young, K. A., Wise, J. A., Johnson, E., Poe, B., Kruse, D. H., … DeSaix, P. (n.d.). Anatomy and Physiology. Houston, Texas: OpenStax. Access for free at: https://openstax.org/details/books/anatomy-and-physiology