Cellular respiration is the fundamental process by which living cells extract energy from glucose, converting it into a usable form known as adenosine triphosphate, or ATP. This process begins with glycolysis, an ancient metabolic pathway that takes place in the cell’s cytoplasm. Glycolysis is the universal first step in energy production for almost all organisms. However, the continuation of this process depends heavily on the availability of oxygen, which necessitates an alternative pathway when oxygen is absent.
Glycolysis: The Initial Energy Harvest
Glycolysis is a ten-step sequence that splits a single six-carbon glucose molecule into two three-carbon molecules of pyruvate. The process yields a net gain of two ATP molecules through substrate-level phosphorylation, a direct transfer of a phosphate group to ADP.
During glycolysis, high-energy electrons are transferred to an electron-carrying molecule. Two molecules of nicotinamide adenine dinucleotide (NAD+) are reduced to two molecules of NADH during the oxidation of glyceraldehyde-3-phosphate. NAD+ acts as an oxidizing agent, accepting electrons and a proton in this step. Cells maintain only a limited reserve of NAD+ in the cytoplasm; once the available supply is converted to NADH, glycolysis would halt completely.
The Necessity of an Alternative Pathway
The fate of the pyruvate and the NADH produced during glycolysis is determined by the presence of oxygen. If oxygen is plentiful, the cell is in an aerobic state, and pyruvate moves into the mitochondria for full oxidation in the citric acid cycle and oxidative phosphorylation. During this subsequent process, NADH molecules deposit their electrons at the electron transport chain, converting them back to NAD+ for reuse.
When oxygen is scarce or completely absent, the electron transport chain cannot function because oxygen is unavailable to act as the final electron acceptor. This anaerobic condition causes NADH to accumulate rapidly within the cytoplasm. Since NADH cannot be re-oxidized to NAD+ by the blocked electron transport chain, the limited pool of NAD+ is depleted. Without a continuous supply of NAD+, the electron-transfer step of glycolysis cannot proceed, stopping the cell’s only source of ATP production under anaerobic conditions.
Fermentation: The Mechanism of NAD+ Recycling
Fermentation is the metabolic pathway that allows glycolysis to proceed by regenerating NAD+ from the accumulated NADH. This process achieves its goal by transferring the electrons from NADH to an organic molecule, rather than to oxygen. The function of fermentation is solely to recycle the NAD+ coenzyme, ensuring the continued operation of glycolysis and the cell’s minimal ATP supply. Fermentation itself does not generate any additional ATP beyond the two molecules already produced by glycolysis.
Lactic Acid Fermentation
The most common form in human muscle cells and certain bacteria is lactic acid fermentation. In this single-step reaction, the enzyme lactate dehydrogenase transfers electrons directly from NADH to pyruvate. This reduces pyruvate to lactate, while simultaneously oxidizing NADH back to NAD+. The regenerated NAD+ is then available to re-enter the glycolytic pathway.
Alcoholic Fermentation
An alternative mechanism, alcoholic fermentation, is common in yeast and some plant cells, and it occurs in two steps. First, the enzyme pyruvate decarboxylase removes a carbon atom from pyruvate, releasing carbon dioxide (CO2) and creating a two-carbon compound called acetaldehyde. In the second step, the enzyme alcohol dehydrogenase transfers electrons from NADH to acetaldehyde. This final reduction converts acetaldehyde into ethanol, oxidizing NADH back to NAD+.
Real-World Applications of Anaerobic Processes
In human muscle cells, the rapid demand for energy during intense exercise can outpace the oxygen supply from the bloodstream. When this oxygen deficit occurs, muscle cells temporarily switch to lactic acid fermentation to maintain a small, continuous supply of ATP, which results in lactate production.
Alcoholic fermentation is a long-standing process in food and beverage industries. Yeast uses this pathway to convert sugars into ethanol, the alcohol found in beer and wine. The carbon dioxide byproduct of the same process causes dough to rise in baking. Other applications include the use of lactic acid bacteria to produce dairy products like yogurt, cheese, and buttermilk. Here, the acid acts as a preservative and contributes to the characteristic flavor and texture.