Summary
Highlights
The Krebs cycle, also known as the tricarboxylic acid (TCA) cycle, is a biochemical pathway central to energy generation through the oxidation of acetyl-CoA. It's also crucial for synthesizing NADH and producing amino acids. In eukaryotes, it occurs in the mitochondria, while in prokaryotes, it happens in the cytosol.
The cycle begins with a preparatory step: pyruvate, derived from the glycolysis of glucose (a six-carbon compound split into two three-carbon pyruvate molecules). Pyruvate is then oxidized into acetyl-CoA by the enzyme pyruvate dehydrogenase complex, producing a molecule of carbon dioxide and NADH. Acetyl-CoA is a two-carbon compound.
Next, acetyl-CoA combines with oxaloacetate (a four-carbon compound) to form citrate (a six-carbon compound). This reaction is catalyzed by citrate synthase. Citrate is then isomerized into isocitrate by the enzyme aconitase.
Isocitrate is oxidized into alpha-ketoglutarate by isocitrate dehydrogenase, reducing NAD to NADH and releasing carbon dioxide, making alpha-ketoglutarate a five-carbon compound. Alpha-ketoglutarate is then converted to succinyl-CoA by alpha-ketoglutarate dehydrogenase, generating another NADH and carbon dioxide, resulting in a four-carbon succinyl-CoA.
Succinyl-CoA is converted to succinate by succinyl-CoA synthase, which generates a molecule of GTP. Succinate is then converted to fumarate by succinate dehydrogenase, producing a molecule of QH2, which is used to form FADH2.
Fumarate is converted into malate by the enzyme fumarase. In the final step, malate is converted back into oxaloacetate by malate dehydrogenase, producing another NADH.
Each turn of the Krebs cycle generates three NADH, one FADH2, one GTP, and two carbon dioxide molecules. Since each glucose molecule yields two pyruvate, the cycle runs twice per glucose, producing a total of six NADH, two FADH2, two GTP, and four carbon dioxide. All NADH and FADH are subsequently used in the electron transport chain to generate ATP.