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The spontaneous direction of a reaction is predicted by the change in free energy (∆G) occurring during the reaction. If ∆G is negative (meaning the product has a lower free energy than the substrate), the reaction will proceed spontaneously. Conversely, if ∆G is positive, the reaction will not be spontaneous. In the case where ∆G = 0, the reaction is said to be in equilibrium. The magnitude of the ∆G for the forward reaction is equal but opposite in sign to that of the reverse reaction. Both the ∆G and standard free energy changes (∆G0) are additive in a sequence of consecutive reactions. Therefore, reactions or processes with a large positive ∆G can be made possible by coupling them with those that have a large negative ∆G, such as ATP hydrolysis. The electron transport chain, which consists of flavin mononucleotide (FMN), iron-sulfur centers, coenzyme Q, and a series of heme-containing cytochromes, is responsible for the transfer of electrons derived from different body fuels to oxygen (O2). This pathway is located in the inner mitochondrial membrane, which is impermeable to most substances. The final step in this pathway involves the reduction of oxygen to water, as oxygen has a large positive reduction potential (E0). Cytochrome c oxidase, the terminal cytochrome, is the only cytochrome capable of binding oxygen. During electron transport, protons (H+) are pumped across the inner mitochondrial membrane from the matrix to the intermembrane space, with 10 H+ being pumped for every NADH oxidized. This process leads to the creation of electrical and pH gradients across the inner mitochondrial membrane. Once the H+ ions have been transferred to the cytosolic side of the membrane, they reenter the matrix through the Fo H+ channel in ATP synthase (Complex V), which dissipates the pH and electrical gradients. This causes conformational changes in the F1 β subunits of the synthase, resulting in the synthesis of ATP from ADP + inorganic phosphate. Electron transport and phosphorylation are closely linked in oxidative phosphorylation (OXPHOS). Inhibition of one process will inhibit the other. These processes can be uncoupled by uncoupling protein-1 in the inner mitochondrial membrane of brown adipocytes, as well as by synthetic compounds like 2,4-dinitrophenol and aspirin, which dissipate the H+ gradient. In uncoupled mitochondria, the energy produced by electron transport is released as heat rather than being used for ATP synthesis. Mutations in mitochondrial DNA, which is inherited from the mother, can be responsible for certain mitochondrial diseases, including Leber hereditary optic neuropathy. The release of cytochrome c into the cytoplasm and subsequent activation of proteolytic caspases leads to apoptotic cell death.

Choose the ONE best answer.
1. In the 1930s, 2,4-dinitrophenol (DNP), an uncoupler of oxidative phosphorylation, was used as a weight-loss agent. However, its use was discontinued in 1939 due to reports of fatal overdoses. Which of the following would most likely be true regarding individuals taking 2,4-DNP?
A. ATP levels in the mitochondria are greater than normal.
B. Body temperature is elevated as a result of hypermetabolism.
C. Cyanide has no effect on electron flow.
D. The proton gradient across the inner mitochondrial membrane is greater than normal.
E. The rate of electron transport is abnormally low.

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The change in free energy (∆G) occurring during a reaction predicts the direction in which that reaction will spontaneously proceed. If ∆G is negative (that is, the product has a lower free energy than the substrate), then the reaction is spontaneous as written. If ∆G is positive, then the reaction is not spontaneous. If ∆G = 0, then the reaction is in equilibrium. The ∆G of the forward reaction is equal in magnitude but opposite in sign to that of the back reaction. The ∆G are additive in any sequence of consecutive reactions, as are the standard free energy changes (∆G0). Therefore, reactions or processes that have a large, positive ∆G are made possible by coupling with those that have a large, negative ∆G such as ATP hydrolysis. The reduced coenzymes nicotinamide adenine dinucleotide (NADH) and flavin adenine dinucleotide (FADH2) each donate a pair of electrons to a specialized set of electron carriers, consisting of flavin mononucleotide (FMN), iron-sulfur centers, coenzyme Q, and a series of heme-containing cytochromes, collectively called the electron transport chain. This pathway is present in the inner mitochondrial membrane (impermeable to most substances) and is the final common pathway by which electrons derived from different fuels of the body flow to oxygen (O2), which has a large, positive reduction potential (E0), reducing it to water. The terminal cytochrome, cytochrome c oxidase, is the only cytochrome able to bind O2. Electron transport results in the pumping of protons (H+) across the inner mitochondrial membrane from the matrix to the intermembrane space, 10 H+ per NADH oxidized. This process creates electrical and pH gradients across the inner mitochondrial membrane. After H+ have been transferred to the cytosolic side of the membrane, they reenter the matrix by passing through the Fo H+ channel in ATP synthase (Complex V), dissipating the pH and electrical gradients and causing conformational changes in the F1 β subunits of the synthase that result in the synthesis of ATP from ADP + inorganic phosphate. Electron transport and phosphorylation are tightly coupled in oxidative phosphorylation ([OXPHOS] Fig. 6.18). Inhibition of one process inhibits the other. These processes can be uncoupled by uncoupling protein-1 of the inner mitochondrial membrane of brown adipocytes and by synthetic compounds such as 2,4-dinitrophenol and aspirin, all of which dissipate the H+ gradient. In uncoupled mitochondria, the energy produced by electron transport is released as heat rather than being used to synthesize ATP. Mutations in mitochondrial DNA, which is maternally inherited, are responsible for some cases of mitochondrial diseases such as Leber hereditary optic neuropathy. The release of cytochrome c into the cytoplasm and subsequent activation of proteolytic caspases results in apoptotic cell death.
Choose the ONE best answer.
.1. 2,4-Dinitrophenol (DNP), an uncoupler of oxidative phosphorylation, was used as a weight-loss agent in the 1930s. Reports of fatal overdoses led to its discontinuation in 1939. Which of the following would most likely be true concerning individuals taking 2,4-DNP?
A. ATP levels in the mitochondria are greater than normal.
B. Body temperature is elevated as a result of hypermetabolism.
C. Cyanide has no effect on electron flow.
D. The proton gradient across the inner mitochondrial membrane is greater than normal.
E. The rate of electron transport is abnormally low.