3rd Unit / Ch 6 Bioenergetics Oxidative Phosphorylation Flashcards
Free Energy Change 6.1
Will the reaction shown proceed spontaneously in the forward (B➔A) or the reverse
(A➔B) direction?
Is the delta G of this reaction positive or negative at equilibrium?
The reaction shown will proceed spontaneously in the reverse (A➔B) direction because the delta G of the forward direction is positive. The forward reaction is endergonic , and it will not proceed unless energy is provided.
At equilibrium , the delta G = 0 (neither positive nor negative). [ Note: Equilibrium is the point at which no net chemical change occurs. Therefore, for A➔B at equilibrium,
the ratio of [B] to [A] is constant regardless of their actual concentrations.]
Free Energy Change 6.1
Compare and contrast delta G and Go
delta G is the capacticyt of a system to do work as it proceeds to equilibrium. delta G can be determined under standard conditions in which the concentration of the
reactants and products is 1M ( delta G 0 ), or it can be determined at any specified concentrations
( delta G ). Thus, delta G 0 is a constant (a reference value) and G is a variable. Their relationship is shown in the equation at bottom right.
Free Energy Change 6.1
Glutamine synthetase catalyzes the amidation of Glu to Gln. However, the reaction is endergonic. How is this problem solved in cells (e.g., skeletal myocytes) that
synthesize Gln?
The problem of glutamine synthesis being endergonic is solved by the production of a common intermediate that couples the glutamine synthetase reaction to the exergonic hydrolysis of ATP, such that the net delta G of the coupled reactions is
negative.
Electron Transport Chain
What is the process of this?
The ETC shown is an assembly of carriers that accept e - from the reduced coenzymes NADH and FADH 2 generated in oxidative processes. As e - move through the ETC to O2 , the terminal acceptor, they release energy that is used to pump H+
across the inner mitochondrial membrane (into the intermembrane space), therebycreating a H+ gradient that drives the phosphorylation of ADP to ATP.
Electron Transport Chain 6.2
What is transferred from NADH to the FMN prosthetic group of NADH dehydrogenase in Complex I?
NADH transfers a hydride ion and a proton (2 e - + 2 H +) to the FMN prosthetic group of NADH dehydrogenase in Complex I of the ETC. The e- are subsequently transferred to CoQ via Fe-S proteins.
Electron Transport Chain 6.2
What are the two relatively mobile e - carriers of the ETC?
CoQ (a lipid-soluble component of the inner membrane) and cytochrome c (a protein in the intermembrane space) are relatively mobile e - carriers of the ETC.
[Note: CoQ accepts e - from several mitochondrial dehydrogenases.]
Electron Transport Chain 6.2
Primary CoQ defi ciency is an AR genetic condition that affects CoQ synthesis. What are the functional consequences of this deficiency?
Primary CoQ deficiency will impede e - transfer from both Complexes I and II, decreasing the production of ATP. This will typically manifest as muscle weakness and exercise intolerance.
Electron Transport Chain 6.3
How do the cytochromes shown transfer e - ? Which one of the Complexes is also called cytochrome c oxidase?
The iron of the heme prosthetic group in cytochromes readily interconverts between the oxidized ferric form (Fe 3 + ) and the reduced ferrous form (Fe 2 + ), enabling cytochromes to transfer e - . Complex IV is called cytochrome c oxidase because the e - acceptor is O2 and not the prosthetic group of a protein.
Complex IV contains Fe (in the heme component) and Cu.
Electron Transport Chain 6.3
Trace the path through Complex II of the e - derived from the oxidation of succinate to fumarate.
The e - from succinate are first transferred to the FAD prosthetic group of Succinate Dehydrogenase, reducing it to FADH2, and then to the Fe 3 + of the Fe-S proteins, reducing it to Fe2+ as the FADH2 is reoxidized. The e - are picked up from the Fe2+ by CoQ , reducing it to CoQH2 as Fe2+ is reoxidized. No H+ are pumped at Complex II.
Electron Transport Chain 6.3
Cyanide poisoning causes a cytotoxic hypoxia in which cells are unable to use O2, even if it is plentiful. Will cyanide poisoning affect the activity of NADH dehydrogenase?
Cyanide binds and inactivates Complex IV. By preventing transfer of e- to O2 , it causes the ETC to “back up,” resulting in accumulation of the reduced forms of its e- carriers. Therefore, NADH dehydrogenase will be inhibited, and the NADH/NAD+ ratio in mitochondria will increase.
[Note: ETC inhibition results in inhibition of ATP synthesis in coupled mitochondria because ATP synthase requires the H+ gradient.]
Electron Transport Chain 6.4
Does the figure show NADH being oxidized or reduced? FMN?
The NADH is being oxidized to NAD+. The FMN is being reduced to FMNH2. Oxidation is the loss of e- and reduction the gain.
Electron Transport Chain 6.4
What is the consequence of the incomplete reduction of O2 to 2 H2O by the ETC as seen in reperfusion injury?
Incomplete reduction of O 2 to 2 H 2 O by the ETC, as seen in reperfusion injury caused by the rapid return of O2 (e.g., with thrombolytic therapy for an MI ), produces ROS (e.g., O2-, H2O2 , and OH ). ROS damage DNA and proteins and cause
lipid peroxidation. [Note: Enzymes such as superoxide dismutase , catalase , and glutathione peroxidase protect cells from ROS.]
Phosphorylation of ADP to ATP 6.5
How is the fl ow of e- through the ETC coupled to ATP synthesis, as shown?
Flow of e- through the ETC results in energy release used to pump H from the mitochondrial matrix to the intermembrane space at Complexes I (4 H+), III (4 H+), and IV (2H+), creating an electrochemical gradient. The energy of the gradient is used to drive the phosphorylation of ADP to ATP by Complex V ( ATP synthase, F 1 /Fo ATPase ). Thus, the gradient is the common intermediate that couples the processes.
Phosphorylation of ADP to ATP 6.5
What will happen to e- fl ow through the ETC in the presence of oligomycin?
Oligomycin inhibits H+ flux through the Fo domain of ATP synthase, thereby inhibiting ATP production at the F1 domain. In coupled mitochondria, inhibition of ATP synthesis inhibits the ETC because of the difficulty of pumping additional H+ against the steep gradient. Flow of e- will eventually stop.
Phosphorylation of ADP to ATP 6.5
A myocardial infarction ( MI ) is usually caused by occlusion of a coronary artery by a thrombus. What would be the immediate effects on the mitochondrial ETC in the event of an MI?
Flow of e- through the ETC requires the reduction of O2 to 2 H2O by Complex IV. As O2 becomes limited during the MI, the ETC slows and stops.
[Note: Thrombolysis allows rapid reperfusion.]
Membrane Transport Systems 6.6
What is the function of the malate-aspartate shuttle shown?
The malate-aspartate shuttle moves reducing equivalents from the cytosol to the mitochondria because the inner mitochondrial membrane lacks a transporter for NADH. Cytosolic
NADH is oxidized as OAA is reduced to malate, for which there is a membrane transporter. Mitochondrial malate is oxidized to OAA as NAD+ is reduced to NADH+ H+.
[Note: The OAA is transaminated to Asp.]
Membrane Transport Systems 6.6
The glycerophosphate shuttle delivers e- to the ETC via FADH2. Is this shuttle more or less
efficient than the malate-aspartate shuttle in generating ATP?
The NADH of the malate-aspartate shuttle is oxidized by Complex I, whereas the FADH2 of the glycerophosphate shuttle is oxidized by CoQ. The P/O ratio for NADH is -3 and forFADH is -2. Therefore, more ATP will be generated using the malate-aspartate shuttle.
[ Note: The lower P/O ratio for FADH 2 refl ects the smaller number of H+ pumped (and, therefore,
fewer ATP made) because FADH2 is not oxidized by Complex I.]
