The Krebs Cycle, also known as the Citric Acid Cycle or the Tricarboxylic Acid (TCA) Cycle, is a central element of aerobic cellular respiration. This cyclical pathway extracts energy from fuel molecules derived from food. Its primary function is to complete the oxidation of these molecules, releasing stored chemical energy. The cycle generates high-energy electron carriers that will power the vast majority of the cell’s energy production, ultimately leading to the synthesis of adenosine triphosphate (ATP), the universal energy currency.
Setting the Stage: Preparation for the Cycle
Before the Krebs Cycle begins, the three-carbon molecule pyruvate, resulting from glucose breakdown, must be transformed into the correct input molecule. Pyruvate is transported into the mitochondrial matrix, the location for the cycle’s enzymatic reactions in eukaryotic cells.
This conversion, often called the link reaction, is catalyzed by the Pyruvate Dehydrogenase Complex. The complex strips a carbon atom from pyruvate, releasing it as carbon dioxide. The remaining two-carbon unit is oxidized, and the released electrons are captured by NAD+, reducing it to NADH.
The resulting two-carbon molecule attaches to Coenzyme A (CoA), forming Acetyl-CoA. Acetyl-CoA is the direct fuel for the Krebs Cycle, carrying the two carbons that will be broken down in subsequent reactions.
The Eight Reactions of the Krebs Cycle
The cycle initiates when the two-carbon Acetyl-CoA joins with the four-carbon acceptor molecule, oxaloacetate, forming the six-carbon compound citrate. This reaction gives the pathway its alternative name, the Citric Acid Cycle. Citrate then undergoes a rearrangement, converting into its isomer, isocitrate.
The next two steps involve oxidative decarboxylation, removing two carbon atoms from the chain, each released as carbon dioxide. First, isocitrate is converted into the five-carbon alpha-ketoglutarate, forming a molecule of NADH. Next, alpha-ketoglutarate is transformed into the four-carbon succinyl-CoA, yielding a second molecule of NADH and another carbon dioxide molecule.
The remaining four-carbon molecule proceeds through four reactions designed to regenerate oxaloacetate. The energy stored in the succinyl-CoA bond is used to generate guanosine triphosphate (GTP), which is convertible to ATP. Succinate is then oxidized to fumarate, capturing electrons on FAD and reducing it to FADH\(_{2}\).
Fumarate is hydrated, converting it into malate. The final reaction completes the cycle by oxidizing malate back into the four-carbon oxaloacetate, ready to accept another Acetyl-CoA molecule. This last oxidation step generates the third and final molecule of NADH.
Harvesting Energy: Outputs of the Cycle
The Krebs Cycle’s primary function is to harvest high-energy electrons from Acetyl-CoA breakdown, not to produce large amounts of immediate energy. For every turn of the cycle, which consumes one Acetyl-CoA molecule, a specific inventory of products is generated.
The cycle produces three molecules of NADH and one molecule of FADH\(_{2}\). Two molecules of carbon dioxide are released as metabolic waste, accounting for the two carbons introduced by Acetyl-CoA. Additionally, one molecule of guanosine triphosphate (GTP) is produced through substrate-level phosphorylation, equivalent to one ATP.
While this single GTP/ATP is the only immediate usable energy, the electron carriers represent a much larger, stored energy potential. The NADH and FADH\(_{2}\) molecules carry their captured electrons to the final stage of cellular respiration. These reduced coenzymes are the most valuable output, serving as the necessary fuel for the process that yields the majority of the cell’s energy.
Connecting the Cycle to Overall Cellular Energy
The importance of the Krebs Cycle lies in its role as the feeder mechanism for the Electron Transport Chain (ETC). The NADH and FADH\(_{2}\) molecules are mobile repositories of electrons, not the final energy product. They travel to the inner mitochondrial membrane and donate their high-energy electrons to protein complexes embedded there.
As these electrons move down the ETC, their energy is systematically released and used to pump hydrogen ions across the membrane, creating a high electrochemical gradient. This gradient stores potential energy. The flow of these hydrogen ions back across the membrane through the specialized enzyme ATP synthase drives the process called oxidative phosphorylation.
This final stage synthesizes the vast bulk of the cell’s ATP, powered almost entirely by the electron carriers supplied by the Krebs Cycle. Though the cycle itself yields only one molecule of immediate ATP, it is indirectly responsible for producing over 90 percent of the energy harvested from the original fuel source. The cycle is an engine, converting the chemical energy of food into the transient electron energy needed to power the cell’s ATP synthesis.