Passage
ATP synthase, also known as Complex V, produces the majority of the ATP in eukaryotic cells. It is a transmembrane protein encoded by both nuclear and mitochondrial genes in humans, and is found in the inner mitochondrial membrane. Complex V consists of over 20 subunits, including three sets of heterodimers arranged in a circle in the mitochondrial matrix. Each dimer contains an α subunit and a β subunit, and each β subunit exists in one of three conformations: one that binds ATP, one that binds ADP and inorganic phosphate, and one that binds neither.As protons flow from the intermembrane space through Complex V and into the matrix, they cause the transmembrane γ subunit to rotate and interact with each β subunit in turn. Four protons provide enough energy for rotation from one β subunit to the next, and each rotation causes a β subunit to release a new ATP molecule as it changes from the ATP-binding to the nonbinding conformation (Figure 1) . Thus 12 protons produce 3 ATP molecules each time the γ subunit makes a complete revolution. Every NADH molecule that enters the electron transport chain (ETC) pumps 10 protons into the intermembrane space for use by Complex V whereas only 6 protons are pumped per FADH₂ molecule.
Figure 1 Depictions of ATP synthase viewed from the side (left) and the bottom (right) Researchers visualized the rotation of the γ subunit by attaching it to a fluorescently labeled actin filament. The observed rotation over time is shown in Figure 2.
Figure 2 Counterclockwise rotation of the γ subunit of ATP synthase (bottom view) over time in seconds as visualized by a fluorescent labelAn L156P mutation in subunit A of Complex V is linked to neuropathy, ataxia, and retinal degeneration. Although the exact molecular bases of these pathological states are unknown, the following hypotheses are currently under study:Hypothesis 1L156P Complex V functions normally but is less abundant than wild-type Complex V.Hypothesis 2The mutation partially decouples proton flow from ATP synthesis.Hypothesis 3The mutation leads to increased oxidative stress from the ETC, resulting in apoptosis.
Adapted from Kucharczyk R, Zick M, Bietenhader M, et al. Mitochondrial ATP synthase disorders: molecular mechanisms and the quest for curative therapeutic approaches. Biochim Biophys Acta. 2009;1793(1) :186-99.
-Based on the information in the passage and Figures 1 and 2, approximately how many protons flow through wild-type Complex V per second under the experimental conditions?

Question

Passage
ATP synthase, also known as Complex V, produces the majority of the ATP in eukaryotic cells. It is a transmembrane protein encoded by both nuclear and mitochondrial genes in humans, and is found in the inner mitochondrial membrane. Complex V consists of over 20 subunits, including three sets of heterodimers arranged in a circle in the mitochondrial matrix. Each dimer contains an α subunit and a β subunit, and each β subunit exists in one of three conformations: one that binds ATP, one that binds ADP and inorganic phosphate, and one that binds neither.As protons flow from the intermembrane space through Complex V and into the matrix, they cause the transmembrane γ subunit to rotate and interact with each β subunit in turn. Four protons provide enough energy for rotation from one β subunit to the next, and each rotation causes a β subunit to release a new ATP molecule as it changes from the ATP-binding to the nonbinding conformation (Figure 1) . Thus 12 protons produce 3 ATP molecules each time the γ subunit makes a complete revolution. Every NADH molecule that enters the electron transport chain (ETC) pumps 10 protons into the intermembrane space for use by Complex V whereas only 6 protons are pumped per FADH₂ molecule.

Figure 1 Depictions of ATP synthase viewed from the side (left) and the bottom (right) Researchers visualized the rotation of the γ subunit by attaching it to a fluorescently labeled actin filament. The observed rotation over time is shown in Figure 2.

Figure 2 Counterclockwise rotation of the γ subunit of ATP synthase (bottom view) over time in seconds as visualized by a fluorescent labelAn L156P mutation in subunit A of Complex V is linked to neuropathy, ataxia, and retinal degeneration. Although the exact molecular bases of these pathological states are unknown, the following hypotheses are currently under study:Hypothesis 1L156P Complex V functions normally but is less abundant than wild-type Complex V.Hypothesis 2The mutation partially decouples proton flow from ATP synthesis.Hypothesis 3The mutation leads to increased oxidative stress from the ETC, resulting in apoptosis.
Adapted from Kucharczyk R, Zick M, Bietenhader M, et al. Mitochondrial ATP synthase disorders: molecular mechanisms and the quest for curative therapeutic approaches. Biochim Biophys Acta. 2009;1793(1) :186-99.
-Based on the information in the passage and Figures 1 and 2, approximately how many protons flow through wild-type Complex V per second under the experimental conditions?

Quizplus · Accepted Answer

11ecba2d_0e3f_ce68_a3bf_bbbd41eaf86a_MD0008_00 In Figure 2, researchers labeled the γ subunit with a fluorescent actin filament. The rotation of the filament corresponds to the rotation of the γ subunit and shows that under the given set of experimental conditions, one complete rotation takes 1 second. The text of the passage and Figure 1 indicate that four protons are required to cause the γ subunit to rotate from one β subunit to the next, releasing one new ATP molecule each time. The complex contains three β subunits arranged in a circle, so one complete revolution corresponds to three ATP released and 12 protons that flow through Complex V. Therefore, the rate of proton flow through wild-type Complex V must be 12 per second. (Choice A) Four protons go through the complex for each 11ecba2d_0e3f_ce69_a3bf_118f8a656a61_MD0008_00 13 of a complete revolution. A complete revolution takes 1 second, so four protons flow through in 11ecba2d_0e3f_f57a_a3bf_c7368cbfb324_MD0008_00 13 of a second. (Choice B) Six protons would be the correct answer if one complete rotation took 2 seconds. However, Figure 2 shows that two complete rotations occur in 2 seconds. (Choice D) Twenty-four protons would be correct if two rotations occurred per second instead of one. Educational objective: The rate of a chemical reaction or process can be calculated by dividing the total output by the time it takes to achieve that output.

Passage ATP Synthase, Also Known as Complex V, Produces the Majority