The second step in cellular respiration, called the Krebs cycle, picks up where glycolysis left off. Recall that in glycolysis, glucose is split into two molecules of pyruvate. Note that these two pyruvate molecules retain the original six carbon atoms from glucose, as well as most of glucose's energy.
Before the Krebs cycle can begin, the pyruvate molecules must be transported from the cytoplasm, where glycolysis occurs, into mitochondria, where the Krebs cycle takes place.
To prepare for the Krebs cycle, pyruvate is modified in three quick steps involving NAD+ and another molecule called coenzyme A. In one of these modifications, carbon dioxide is released from pyruvate and eventually exhaled from the body. In the other modifications, the 2-carbon molecule that remains is attached to coenzyme A, while a proton (also called a hydrogen ion) and high energy electrons are donated to NAD+, yielding the high-energy electron carrier NADH. The new molecule is called acetyl-CoA. Because two pyruvate molecules emerged from glycolysis, two acetyl-CoA molecules and two NADH are now formed. Note that two of the six carbon atoms from glucose are now in the form of two carbon dioxide molecules.
Acetyl-CoA enters the Krebs cycle, where the remaining four carbon atoms that originated from glucose will soon be released as carbon dioxide. In the first step of this pathway, acetyl-CoA combines with water and a molecule called oxaloacetate. The first outcome of the Krebs cycle is the production of a molecule with six carbon atoms—four from oxaloacetate and two that originated from glucose.
This six-carbon molecule is rearranged by the removal and then the addition of water. Another important outcome of the Krebs cycle occurs next, when the molecule is stripped of two molecules of carbon dioxide, which are exhaled. At the same time, high-energy electrons and protons are donated to molecules of NAD+, creating NADH molecules.
Another important outcome of the Krebs cycle occurs in the next reaction, which draws energy from the remaining molecule to join inorganic phosphate and ADP into a molecule of ATP.
In addition to NAD+, another molecule called FAD plays a role in as a high-energy electron carrier. The four-carbon molecule donates protons and high-energy electrons to these carriers. The molecule then becomes slightly rearranged by the addition of water, after which more electrons and a proton join with NAD+ to form NADH. The final outcome of the Krebs cycle is the re-formation of the cycle's starting molecule, oxaloacetate.
The entire cycle occurs again with the second acetyl-CoA molecule. As the second round continues, more NADH, more carbon dioxide, more ATP, and more FADH2 molecules result. If these molecules are added to those made from the preparation reactions, we can see that all six of the carbon atoms from glucose have been released in the form of carbon dioxide. Although a small amount of ATP has been formed in the Krebs cycle, it is the NADH and FADH2 molecules that represent the most energy for the cell.
These electron carriers enter the next phase of cellular respiration, called the electron transport chain. NADH and FADH2 molecules must give up their extra electrons to the electron transport chain so that they may revert back to NAD+ and FAD and help in the Krebs cycle again. The electron transport chain uses the energy from the electrons to produce a large number of ATP molecules. Note that the electron transport chain absolutely requires oxygen to operate. Because the Krebs cycle relies on a functioning electron transport chain to accept electrons from NADH and FADH2, the Krebs cycle will shut down along with the electron transport chain if oxygen disappears.
Aerobic training can cause our bodies to produce more mitochondria in muscle cells. Why might this be beneficial?
An increase in mitochondria means that the cell has more cellular machinery to perform the Krebs cycle and the electron transport chain. Because so much ATP is produced in the electron transport chain, such an increase in mitochondria can provide the cell with more energy to sustain physical activity, provided oxygen is available.