The Energy Yield from the Oxidationof Fatty Acids
In carbohydrate metabolism, the energy released by oxidation reactions is used to drive the production of ATP, with most of the ATP produced in aerobic processes. In the same aerobic processes—namely, the citric acid cycle and oxidative phosphorylation—the energy released by the oxidation of acetyl-CoA formed by β-oxidation of fatty acids can also be used to produce ATP. There are two sources of ATP to keep in mind when calculating the overall yield of ATP. The first source is the reoxidation of the NADH and FADH2 produced by the β-oxidation of the fatty acid to acetyl-CoA. The second source is ATP production from the processing of the acetyl-CoA through the citric acid cycle and oxidative phosphorylation. We shall use the oxidation of stearic acid, which contains 18 carbon atoms, as our example.
Eight cycles of β-oxidation are required to convert one mole of stearic acid to nine moles of acetyl-CoA; in the process eight moles of FAD are reduced to FADH2, and eight moles of NAD+ are reduced to NADH.
The nine moles of acetyl-CoA produced from each mole of stearic acid enter the citric acid cycle. One mole of FADH2 and three moles of NADH are produced for each mole of acetyl-CoA that enters the citric acid cycle. At the same time, one mole of GDP is phosphorylated to produce GTP for each turn of the citric acid cycle.
The FADH2 and NADH produced by β-oxidation and by the citric acid cycle enter the electron transport chain, and ATP is produced by oxidative phosphorylation. In our example, there are 17 moles of FADH2 (8 from β-oxidation and 9 from the citric acid cycle); there are also 35 moles of NADH (8 from β-oxidation and 27 from the citric acid cycle). Recall that 2.5 moles of ATP are produced for each mole of NADH that enters the electron transport chain, and 1.5 moles of ATP result from each mole of FADH2. Because 17 - > 1.5 = 25.5 and 35 - > 2.5 = 87.5, we can write the following equations:
The overall yield of ATP from the oxidation of stearic acid can be obtained by adding the equations for β-oxidation, for the citric acid cycle, and for oxidative phosphorylation. In this calculation, we take GDP as equivalent to ADP and GTP as equivalent to ATP, which means that the equivalent of nine ATP must be added to those produced in the reoxidation of FADH2 and NADH. There are 9 ATP equivalent to the 9 GTP from the citric acid cycle, 25.5 ATP from the reoxidation of FADH2, and 87.5 ATP from the reoxidation of NADH, for a grand total of 122 ATP.
The activation step in which stearyl-CoA was formed is not included in this calculation, and we must subtract the ATP that was required for that step. Even though only one ATP was required, two high-energy phosphate bonds are lost because of the production of AMP and PPi. The pyrophosphate must be hydro-lyzed to phosphate (Pi) before it can be recycled in metabolic intermediates. As a result, we must subtract the equivalent of two ATP for the activation step. The net yield of ATP becomes 120 moles of ATP for each mole of stearic acid that is completely oxidized. See Table 21.1 for a balance sheet. Keep in mind that these values are theoretical consensus values that not all cells attain.
As a comparison, note that 32 moles of ATP can be obtained from the com-plete oxidation of one mole of glucose; but glucose contains 6, rather than 18, carbon atoms. Three glucose molecules contain 18 carbon atoms, and a more interesting comparison is the ATP yield from the oxidation of three glucose molecules, which is - > 3 32 = 96 ATP for the same number of carbon atoms. The yield of ATP from the oxidation of the lipid is still higher than that from the carbohydrate, even for the same number of carbon atoms. The reason is that a fatty acid is all hydrocarbon except for the carboxyl group; that is, it exists in a highly reduced state.
A sugar is already partly oxidized because of the presence of its oxygen-containing groups. Because the oxidation of a fuel leads to the reduced electron carriers used in the electron transport chain, a more reduced fuel, such as a fatty acid, can be oxidized further than a partially oxidized fuel, such as a carbohydrate.
Another point of interest is that water is produced in the oxidation of fatty acids. We have already seen that water is also produced in the complete oxida-tion of carbohydrates. The production of metabolic water is a common feature of aerobic metabolism. This process can be a source of water for organisms that live in desert environments. Camels are a well-known example; the stored lipids in their humps are a source of both energy and water during long trips through the desert. Kangaroo rats provide an even more striking example of adaptation to an arid environment. These animals have been observed to live indefinitely without having to drink water. They live on a diet of seeds, which are rich in lipids but contain little water. The metabolic water that kangaroo rats produce is adequate for all their water needs. This metabolic response to arid conditions is usually accompanied by a reduced output of urine.
The complete oxidation of fatty acids by the citric acid cycle and the elec-tron transport chain releases large amounts of energy.
When we include the reoxidation of NADH and FADH2 from β-oxidation and the citric acid cycle, we obtain a net yield of 120 ATP for a single molecule of stearic acid.