Many eukaryotes, including humans, are obligate aerobes: they grow only in the presence of molecular oxygen and can metabolize glucose (or related sugars) completely to CO2, with the concomitant production of a large amount of ATP. Most eukaryotes, however, can generate some ATP by anaerobic metabolism. A few eukaryotes are facultative anaerobes: they grow in either the presence or the absence of oxygen. Annelids (segmented worms), mollusks, and some yeasts, for example, can survive without oxygen, relying on the ATP produced by fermentation.
In the absence of oxygen, yeasts convert the pyruvate produced by glycolysis to one molecule each of ethanol and CO2; in these reactions, two NADH molecules are oxidized to NAD+ for every two pyruvates converted to ethanol, thereby regenerating the supply of NAD+, which is necessary for glycolysis to continue (Figure 1a, left). This anaerobic catabolism of glucose, called fermentation, is the basis of beer and wine production.
Fig1. Anaerobic versus aerobic metabolism of glucose. The ultimate fate of pyruvate formed during glycolysis depends on the presence or absence of oxygen. (a) In the absence of oxygen, pyruvate is only partially degraded and no further ATP is made. However, two electrons are transferred from each NADH molecule produced during glycolysis to an acceptor molecule to regenerate NAD+, which is required for continued glycolysis. In yeast (left), acetaldehyde is the electron acceptor and ethanol is the product. This process is called alcoholic fermentation. When oxygen is scarce in muscle cells (right), NADH reduces pyruvate to form lactic acid, regenerating NAD+, a process called lactic acid fermentation. (b) In the presence of oxygen, pyruvate is transported into mitochondria, where it is first converted by pyruvate dehydrogenase into one molecule of CO2 and one of acetic acid, the latter linked to coenzyme A (CoA-SH) to form acetyl CoA, concomitant with reduction of one molecule of NAD+ to NADH. Further metabolism of acetyl CoA and NADH generates approximately an additional 28 molecules of ATP per glucose molecule oxidized.
Fermentation also occurs in animal cells, although lactic acid, rather than alcohol, is the product. During prolonged contraction of mammalian skeletal muscle cells—for example, during exercise—oxygen can become scarce within the muscle tissue. As a consequence, glucose catabolism is limited to glycolysis, and muscle cells convert pyruvate to two molecules of lactic acid by a re duction reaction that also oxidizes two NADHs to two NAD+s (Figure 1a, right). Although the lactic acid is released from the muscle into the blood, if the contractions are sufficiently rapid and strong, the lactic acid can transiently accumulate in the tissue and contribute to muscle and joint pain during exercise. Once it is secreted into the blood, some of the lactic acid passes into the liver, where it is reoxidized to pyruvate and either further metabolized to CO2 aerobically or converted back to glucose. Much lactate is metabolized to CO2 by the heart, which is highly perfused by blood and can continue aerobic metabolism at times when exercising, oxygen-poor skeletal muscles secrete lactate. If too much lactic acid accumulates in the blood, the acid causes an unhealthy decrease in the pH of the blood (lactic acidosis). Lactic acid bacteria (the organisms that spoil milk) and other prokaryotes also generate ATP by the fermentation of glucose to lactic acid.
Fermentation is a much less efficient way to generate ATP than aerobic oxidation and therefore occurs in animal cells only when oxygen is scarce. In the presence of oxygen, pyruvate formed by glycolysis is transported into mitochondria, where it is oxidized by O2 to CO2 and H2O via the series of reactions outlined in Figure 1b. This aerobic metabolism of glucose, which occurs in stages II–IV of the process outlined in Figure 2, generates an estimated 28 additional ATP molecules per original glucose molecule, far out stripping the ATP yield from anaerobic glucose metabolism (fermentation).
Fig2. Overview of aerobic oxidation and photosynthesis. Eukaryotic cells use two fundamental mechanisms to convert external sources of energy into ATP. (Top) In aerobic oxidation, “fuel” molecules [primarily sugars and fatty acids (lipids)] undergo preliminary processing in the cytosol, such as breakdown of glucose to pyruvate (stage I), and are then transferred into mitochondria, where they are converted by oxidation with O2 to CO2 and H2O (stages II and III) and ATP is generated (stage IV). (Bottom) In photosynthesis, which occurs in chloroplasts, the radiant energy of light is absorbed by specialized pigments (stage 1); the absorbed energy is used both to oxidize H2O to O2 and to establish conditions (stage 2) necessary for the generation of ATP (stage 3) and of carbohydrates from CO2 (carbon fixation, stage 4). Both mechanisms involve the production of reduced high-energy electron carriers (NADH, NADPH, FADH2) and the movement of electrons down an electric potential gradient in an electron-transport chain through specialized membranes. Energy released from these electrons is captured as a pro ton electrochemical gradient (proton-motive force) that is then used to drive ATP synthesis. Bacteria use comparable processes.
