The tricarboxylic acid cycle (TCA), also known as the Krebs cycle or Citric Acid Cycle, is a central metabolic pathway in aerobic cellular respiration. This cyclical series of reactions takes place in the mitochondrial matrix of eukaryotic cells. Its primary purpose is to fully oxidize carbon atoms derived from nutrients, harvesting high-energy electrons by reducing specialized carrier molecules. These carriers then proceed to the final stage of respiration for energy generation.
Preparing the Cycle: Formation of Acetyl-CoA
Before the cycle begins, pyruvate, the three-carbon product of glycolysis, undergoes a preparatory step called oxidative decarboxylation. This process converts pyruvate into the two-carbon compound \(\text{acetyl-CoA}\), catalyzed by the pyruvate dehydrogenase complex. The reaction removes a carboxyl group from pyruvate, releasing it as carbon dioxide, and the remaining acetyl group attaches to coenzyme A. During this oxidation, electrons are transferred to the carrier \(\text{NAD}^+\), reducing it to \(\text{NADH}\). Thus, one molecule of \(\text{NADH}\) is produced for every molecule of pyruvate converted into \(\text{acetyl-CoA}\).
Electron Release Points Within the TCA Cycle
The TCA cycle is a sequence of eight reactions that completes the oxidation of the \(\text{acetyl-CoA}\) unit. One full turn involves four distinct redox reactions where electrons are stripped from the carbon intermediates. The first two electron-releasing steps are coupled with the release of carbon dioxide, fully oxidizing the two carbon atoms that entered the cycle. The first occurs when isocitrate is converted to \(\alpha\)-ketoglutarate, and the second when \(\alpha\)-ketoglutarate is converted to succinyl-CoA. In both reactions, electrons are transferred to \(\text{NAD}^+\), forming \(\text{NADH}\).
A third electron pair is removed when succinate is oxidized to fumarate. Here, the electron acceptor is flavin adenine dinucleotide (\(\text{FAD}\)), which is reduced to \(\text{FADH}_2\). The enzyme succinate dehydrogenase catalyzes this reaction. The final electron-releasing step occurs when malate is oxidized to regenerate oxaloacetate, reducing \(\text{NAD}^+\) to \(\text{NADH}\). In total, one turn of the TCA cycle produces three molecules of \(\text{NADH}\) and one molecule of \(\text{FADH}_2\), resulting in a total release of eight high-energy electrons.
The Journey to ATP: The Significance of Electron Carriers
The \(\text{NADH}\) and \(\text{FADH}_2\) molecules act as temporary storage units, transporting captured high-energy electrons to the inner mitochondrial membrane. This membrane hosts the electron transport chain (ETC), the final stage of aerobic respiration. In the ETC, the carriers surrender their electron pairs to a series of protein complexes. As electrons move through the complexes, the released energy is used to pump hydrogen ions (protons) from the matrix into the intermembrane space. This continuous pumping establishes an electrochemical gradient known as the proton-motive force.
The flow of protons back across the membrane powers the enzyme \(\text{ATP}\) synthase, a process called oxidative phosphorylation, which synthesizes the vast majority of the cell’s \(\text{ATP}\). \(\text{NADH}\) donates electrons at the start of the ETC, passing through all three major proton-pumping complexes. This supports the synthesis of approximately \(2.5\) molecules of \(\text{ATP}\). \(\text{FADH}_2\) enters the chain later, bypassing the first complex, and typically supports the synthesis of about \(1.5\) molecules of \(\text{ATP}\).