Pyruvic acid, often called pyruvate, is the molecule that connects the initial phase of energy extraction from food to the main engine of cellular power generation. It is a three-carbon compound produced when the cell breaks down a six-carbon sugar, like glucose, through a process called glycolysis. This initial breakdown occurs in the cytoplasm, the fluid inside the cell, and represents the first step in converting chemical energy into a usable form. The overall goal of this process, known as cellular respiration, is to synthesize adenosine triphosphate (ATP), the universal energy currency that powers nearly all cellular activities. Pyruvic acid acts as a molecular checkpoint, determining whether the cell will proceed into the oxygen-dependent, high-yield energy production phase within the mitochondria.
The Necessary Step Before the Cycle
Pyruvic acid does not enter the Krebs Cycle directly; it must first undergo a preparatory transformation called pyruvate oxidation. Once generated in the cytoplasm, the three-carbon pyruvate molecule is actively transported into the mitochondrial matrix. This step is a decarboxylation reaction, meaning a carbon atom is removed and released as carbon dioxide (\(\text{CO}_2\)). The release of \(\text{CO}_2\) accounts for some of the gas we exhale.
The remaining two-carbon fragment is then oxidized. Electrons are stripped away and captured by the electron carrier \(\text{NAD}^+\), reducing it to \(\text{NADH}\), a temporary energy storage unit. Finally, the two-carbon unit, now an acetyl group, is attached to Coenzyme A (CoA), forming Acetyl-CoA. This preparatory step yields one Acetyl-CoA, one \(\text{CO}_2\), and one \(\text{NADH}\) per molecule of pyruvate, preparing the carbon fuel for its complete breakdown in the cycle.
The Eight Stages of the Cycle
The Acetyl-CoA molecule is the fuel that enters the Krebs Cycle, also known as the Citric Acid Cycle, inside the mitochondrial matrix. The cycle begins when the two-carbon acetyl group combines with a four-carbon molecule called oxaloacetate (OAA). This condensation reaction forms a six-carbon compound known as citrate, which gives the cycle its alternative name. Coenzyme A is released during this reaction, allowing it to be recycled and pick up another acetyl group.
Citrate then proceeds through seven additional enzyme-catalyzed chemical transformations. This sequence is a true cycle because the final product, oxaloacetate, is the same molecule that started the process, ready to combine with a new Acetyl-CoA molecule. The purpose of these steps is the complete dismantling of the six-carbon molecule through a series of oxidation and decarboxylation reactions.
During the cycle, the two carbons that entered as Acetyl-CoA are fully released as two molecules of \(\text{CO}_2\). At four specific points, energy is harvested by transferring high-energy electrons to carrier molecules. Three molecules of \(\text{NAD}^+\) are reduced to \(\text{NADH}\), and one molecule of \(\text{FAD}\) is reduced to \(\text{FADH}_2\). These electron carriers are responsible for the bulk of the energy yield later on.
The cycle also produces a small amount of direct energy through substrate-level phosphorylation in one of its eight steps. This reaction generates one molecule of guanosine triphosphate (\(\text{GTP}\)), which is functionally equivalent to \(\text{ATP}\) and is quickly converted into it. Therefore, for every turn of the cycle, the cell gains two \(\text{CO}_2\) molecules, three \(\text{NADH}\) molecules, one \(\text{FADH}_2\) molecule, and one \(\text{ATP}\) (or \(\text{GTP}\)) molecule.
The Final Energy Yield
The Acetyl-CoA derived from each pyruvic acid molecule is completely oxidized in the Krebs Cycle, yielding only a single \(\text{ATP}\) molecule. The function of the cycle is primarily to generate a supply of electron carriers, \(\text{NADH}\) and \(\text{FADH}_2\). Since one glucose molecule yields two pyruvic acids, the Krebs Cycle runs twice, producing a total of six \(\text{NADH}\) and two \(\text{FADH}_2\) molecules.
These electron carriers hold the vast majority of the energy originally stored in the pyruvic acid’s chemical bonds. They immediately transfer their high-energy electrons to the Electron Transport Chain (\(\text{ETC}\)), the final stage of cellular respiration, located on the inner mitochondrial membrane. The flow of these electrons powers the creation of a proton gradient across the membrane. This gradient is then used by the enzyme \(\text{ATP}\) synthase to generate the largest output of \(\text{ATP}\), producing approximately 26 to 30 \(\text{ATP}\) molecules from the carriers generated by the two pyruvic acids.