- The Krebs cycle, also known as the citric acid cycle or tricarboxylic acid (TCA) cycle, is a central metabolic pathway that plays a crucial role in cellular respiration—the process by which cells generate energy from nutrients. This cycle occurs in the mitochondrial matrix of eukaryotic cells and is the final common pathway for the oxidation of carbohydrates, fats, and proteins. The primary function of the Krebs cycle is to produce high-energy electron carriers—NADH and FADH₂—which feed into the electron transport chain to drive the production of ATP (adenosine triphosphate), the cell’s main energy currency.
- The cycle begins when acetyl-CoA, a two-carbon molecule derived from the breakdown of glucose (via glycolysis), fatty acids, or amino acids, combines with a four-carbon compound called oxaloacetate to form a six-carbon compound, citrate. This reaction is catalyzed by the enzyme citrate synthase. Through a series of enzymatic steps, citrate is gradually converted back into oxaloacetate, completing the cycle. During this transformation, two carbon atoms are released as carbon dioxide (CO₂), and energy-rich molecules—three NADH, one FADH₂, and one GTP (or ATP)—are generated per acetyl-CoA molecule.
- The steps of the Krebs cycle include several important reactions. Citrate is first isomerized to isocitrate by aconitase. Then, isocitrate dehydrogenase catalyzes the oxidative decarboxylation of isocitrate to α-ketoglutarate, releasing the first molecule of CO₂ and producing NADH. α-Ketoglutarate dehydrogenase then converts α-ketoglutarate to succinyl-CoA, releasing another CO₂ and generating another NADH. Succinyl-CoA is converted to succinate by succinyl-CoA synthetase, producing GTP (or ATP). Next, succinate dehydrogenase oxidizes succinate to fumarate, generating FADH₂. Fumarate is then hydrated to malate by fumarase, and finally, malate dehydrogenase oxidizes malate to oxaloacetate, producing the third NADH.
- Overall, for each acetyl-CoA molecule entering the cycle, the Krebs cycle yields three NADH, one FADH₂, one GTP (or ATP), and two CO₂ molecules. Since each glucose molecule generates two acetyl-CoA molecules, the full oxidation of one glucose via the Krebs cycle produces six NADH, two FADH₂, two ATP (or GTP), and four CO₂ molecules.
- The NADH and FADH₂ molecules generated by the Krebs cycle are then utilized in the electron transport chain, where they donate electrons to generate a proton gradient across the mitochondrial membrane, ultimately leading to the synthesis of additional ATP through oxidative phosphorylation. Thus, the Krebs cycle is vital not only for energy production but also for providing intermediates used in biosynthetic pathways, such as amino acid synthesis and gluconeogenesis.
- In summary, the Krebs cycle is a key metabolic hub that links various biochemical pathways and provides the reducing power necessary for efficient ATP production. It reflects the intricate biochemical coordination essential for maintaining cellular energy balance and supporting life processes.
