5.2: Fermentation

When the average person hears the word “fermentation” he probably thinks about alcohol. As you no doubt recall, glycolysis gave us some usable energy in the form of ATP, and then there are the other products, NADH and pyruvate. As we shall see in the next section, if the cell is eukaryotic and oxygen is available, then those molecules can help make more ATP. If no oxygen is available or the cell is just a lowly prokaryote, it undergoes fermentation to produce either lactate or ethyl alcohol. Why does the cell need lactate or ethanol? It doesn’t, although the lactate can contribute to overall metabolism. What the cells do need is NAD⁺ so that glycolysis can continue beyond step 6. Without fermentation, continued glycolysis would convert all of the NAD⁺ to NADH, and then be stuck, unable to continue. So the primary reason for fermentation, whichever path it takes, is to regenerate NAD⁺ from the NADH.

Lactate Fermentation

In lactate fermentation, the pyruvate is converted to lactate by lactate dehydrogenase. This reaction requires the oxidation of NADH, which thus provides NAD⁺ to the cell for continued glycolysis.

For many cells, the lactate is a waste product and excreted. In fact, this is the case with most muscles: the lactate is carried by the blood from the muscle cells to the liver, where it can be converted to glucose. Thus, although lactate is formed at high rates when muscles are overworked and become fatigued, it is not directly the cause of muscle fatigue. As oxygen availability cannot keep up with aerobic ATP production, and larger and larger proportions of the ATP generated come from glycolysis with fermentation. The current model of muscle fatigue posits that it is due to acidification of the muscle cell as it undergoes rapid glycolysis.

However, in some tissues and cell types, particularly in the heart and brain of higher animals, cell membranes are highly permeable to lactate, the cells can readily convert the lactate to pyruvate, and since these are highly oxygenated tissues, the pyruvate is then used for the TCA cycle and oxidative phosphorylation to generate ATP. In fact, some non-neuronal support cells in the brain (astrocytes) generate and excrete copious lactate which is taken up by the neighboring neurons to fuel ATP production.

Alcohol Fermentation

In alcohol fermentation, pyruvate is first acted upon by pyruvate decarboxylase, which liberates a CO₂ molecule and produces acetaldehyde. Acetaldehyde is then acted upon by alcohol dehydrogenase, using NADH, generating NAD⁺ and ethanol. Here, like with lactate fermentation, the desired product is the regenerated NAD⁺. Ethanol is excreted, and in most animals, is converted to acetaldehyde and then acetic acid, before finally ending up as acetyl-CoA.

As with glycolysis, fermentation can and does take place in cells that are able to make ATP by oxidative phosphorylation. The relative contribution of glycolysis and oxidative phosphorylation to the cellular ATP pool is determined dynamically by physiological conditions.