5. Oxidative Phosphorylation, Respiratory Chain and Krebs Cycle

Question 1 What is bioenergetics?

The transfer and utilization of energy in biologic systems.

Question 2 What does change in enthalpy, ΔH, measure?

The change in heat content of reactants and products.

Question 3 What does change in entropy, ΔS, measure?

The change in randomness or disorder of reactants and products.

Question 4 What does change in free energy, ΔG, represent?

Energy available to do work.

Question 5 What can ΔG predict?

The direction in which a reaction will spontaneously proceed and whether it is favorable.

Question 6 What happens to ΔG as a reaction reaches equilibrium?

It approaches zero.

Question 7 What is the relationship among ΔG, ΔH, T, and ΔS?

ΔG = ΔH − TΔS.

Question 8 What does T represent in the free-energy equation?

Absolute temperature in Kelvin.

Question 9 What is standard free-energy change, ΔG°?

The free-energy change under standard conditions.

Question 10 What standard conditions are listed for ΔG°?

Reactants and products at 1 M, 25°C or 298 K, and 1 atmosphere pressure.

Question 11 What is the relationship between ΔG° and equilibrium constant?

ΔG° = −RT ln Keq.

Question 12 What does a negative ΔG indicate?

An exergonic, spontaneous reaction with net loss of free energy.

Question 13 What does a positive ΔG indicate?

An endergonic, nonspontaneous reaction with net gain of energy.

Question 14 What does ΔG = 0 indicate?

Equilibrium, where forward and backward reaction rates are equal.

Question 15 What happens to free-energy changes when reactions are coupled?

The ΔG values are additive.

Question 16 How can an endergonic reaction proceed in a pathway?

By coupling to a sufficiently exergonic reaction so the overall ΔG is negative.

Question 17 What is ATP?

Adenosine triphosphate, the energy currency of the cell.

Question 18 What is ATP structurally?

An adenosine molecule with three phosphate groups.

Question 19 What is the major role of ATP?

Transfer of free energy from higher-energy substances to lower-energy processes.

Question 20 What does ATP hydrolysis produce in the reaction emphasized in the handout?

ADP and inorganic phosphate.

Question 21 What are the two major ways ATP is produced?

Substrate-level phosphorylation and oxidative phosphorylation.

Question 22 What is substrate-level phosphorylation?

Direct transfer of a phosphate group from a high-energy substrate to ADP.

Question 23 Where can substrate-level phosphorylation occur?

In both the cytosol and mitochondria.

Question 24 Which glycolytic enzymes generate ATP by substrate-level phosphorylation according to the handout?

Phosphoglycerate kinase and pyruvate kinase.

Question 25 Which TCA-cycle step generates a high-energy phosphate directly?

The succinyl thiokinase/succinyl-CoA synthetase step.

Question 26 What is oxidative phosphorylation?

ATP synthesis driven by energy from oxidation through the mitochondrial respiratory chain.

Question 27 Where does oxidative phosphorylation occur?

In mitochondria.

Question 28 Does oxidative phosphorylation require oxygen?

Yes.

Question 29 What is the final substance reduced in oxidative phosphorylation?

Molecular oxygen.

Question 30 Which ATP-producing mechanism is the greatest quantitative source of high-energy phosphate in aerobic organisms?

Oxidative phosphorylation.

Question 31 What are the four major structural parts of the mitochondrion emphasized in the handout?

Outer membrane, inner membrane, cristae, and matrix.

Question 32 How permeable is the outer mitochondrial membrane?

Freely permeable to most molecules.

Question 33 How permeable is the inner mitochondrial membrane?

Impermeable to most molecules.

Question 34 What is the function of mitochondrial cristae?

They increase surface area.

Question 35 What does the mitochondrial matrix contain?

Enzymes, mitochondrial DNA, mitochondrial RNA, and mitochondrial ribosomes.

Question 36 Why do mitochondrial disorders severely affect muscle and nervous tissue?

These tissues have high ATP requirements.

Question 37 What is the electron transport chain?

The final common pathway by which electrons from different body fuels flow to oxygen.

Question 38 Where is the ETC located?

The inner mitochondrial membrane.

Question 39 What two electron carriers feed reducing equivalents into the ETC?

NADH and FADH2.

Question 40 What oxidized coenzymes accept electrons to become NADH and FADH2?

NAD+ and FAD.

Question 41 From which vitamin is NADH derived?

Niacin, vitamin B3.

Question 42 From which vitamin is FADH2 derived?

Riboflavin, vitamin B2.

Question 43 Which ETC components are mobile rather than fixed in the inner membrane?

Coenzyme Q and cytochrome c.

Question 44 What is the only nonprotein component of the ETC according to the handout?

Ubiquinone, or coenzyme Q.

Question 45 What is Complex I called?

NADH dehydrogenase or NADH:CoQ oxidoreductase.

Question 46 What is Complex II called?

Succinate dehydrogenase.

Question 47 What is Complex III called?

Cytochrome b-c1 complex or CoQ:c1 oxidoreductase.

Question 48 What is Complex IV called?

Cytochrome c oxidase.

Question 49 What is Complex V?

ATP synthase.

Question 50 Which ETC complex contains cytochrome aa3 and copper?

Complex IV.

Question 51 Which ETC complexes pump protons into the intermembrane space?

Complexes I, III, and IV.

Question 52 Does Complex II pump protons in the handout's ETC scheme?

No.

Question 53 What is the final electron acceptor of the ETC?

Oxygen.

Question 54 What does oxygen become after accepting electrons and protons at the end of the ETC?

Water.

Question 55 What is the Mitchell hypothesis?

The chemiosmotic hypothesis explaining how electron transport energy is used to make ATP from ADP and Pi.

Question 56 What gradients are created across the inner mitochondrial membrane by the ETC?

An electrical gradient and a pH/proton gradient.

Question 57 What happens to proton concentration in the intermembrane space during ETC activity?

It increases.

Question 58 What happens to the electrical charge of the intermembrane space relative to the matrix?

It becomes more positive.

Question 59 How do protons return to the mitochondrial matrix?

Through ATP synthase, Complex V.

Question 60 What is produced when protons flow through ATP synthase?

ATP.

Question 61 What happens to ETC activity during tissue hypoxia?

It decreases because oxygen is lacking.

Question 62 How does ATP production shift during tissue hypoxia?

From oxidative phosphorylation toward substrate-level phosphorylation.

Question 63 Why are neurons and cardiac muscle especially vulnerable to hypoxia?

Anaerobic glycolysis cannot supply enough ATP for their high energy demands.

Question 64 What are ETC inhibitors?

Compounds that block electron passage by binding components of the ETC and stopping redox reactions.

Question 65 What happens to oxygen consumption when the ETC is inhibited?

It decreases.

Question 66 What happens to the intracellular NADH/NAD+ ratio when the ETC is inhibited?

It increases.

Question 67 What happens to the FADH2/FAD ratio when the ETC is inhibited?

It increases.

Question 68 Why do NADH and FADH2 accumulate during ETC inhibition?

They cannot transfer their electrons through the blocked chain.

Question 69 What happens to ATP production during ETC inhibition?

It decreases.

Question 70 What inhibits Complex I according to the handout?

Barbiturates, piericidin A, amytal, and rotenone.

Question 71 What inhibits Complex II according to the handout?

Malonate, carboxin, and TTFA.

Question 72 What inhibits Complex III?

Antimycin A and dimercaprol.

Question 73 What inhibits Complex IV?

Cyanide, carbon monoxide, sodium azide, and hydrogen sulfide.

Question 74 Why can inhibition of Complex III or IV be rapidly fatal?

Electrons can no longer reach oxygen, stopping the ETC and ATP production.

Question 75 What are uncouplers?

Compounds that increase inner mitochondrial membrane permeability to protons.

Question 76 What happens to electron transport in the presence of an uncoupler?

It proceeds rapidly without maintaining a proton gradient.

Question 77 What happens to oxygen consumption during uncoupling?

It increases.

Question 78 What happens to ATP synthesis during uncoupling?

It decreases.

Question 79 What happens to the NADH/NAD+ ratio during uncoupling according to the handout?

It decreases.

Question 80 Where does the energy go during uncoupling instead of ATP synthesis?

It is released as heat.

Question 81 What synthetic uncoupler is listed in the handout?

2,4-dinitrophenol.

Question 82 What common drug is listed as an uncoupler at toxic doses?

Aspirin.

Question 83 What physiologic uncoupling protein is found in brown fat?

Thermogenin.

Question 84 Why can aspirin overdose cause hyperpyrexia according to the handout?

ETC uncoupling increases heat production.

Question 85 Why is thermogenin important in neonates?

It produces heat by nonshivering thermogenesis and helps prevent hypothermia.

Question 86 What is the direct ATP synthase inhibitor listed in the handout?

Oligomycin.

Question 87 What happens to the proton gradient when ATP synthase is blocked by oligomycin?

It continues to rise initially.

Question 88 Why does the ETC eventually stop after ATP synthase inhibition?

The proton gradient becomes too high for ETC complexes to continue pumping protons.

Question 89 What does atractyloside inhibit?

The transporter that brings ADP into and ATP out of the mitochondrion.

Question 90 How does atractyloside affect oxidative phosphorylation?

It inhibits oxidative phosphorylation by blocking ADP/ATP transport.

Question 91 What are reactive oxygen species?

Unstable partially reduced products of molecular oxygen formed as ETC byproducts.

Question 92 What three ROS are listed in the handout?

Superoxide, hydrogen peroxide, and hydroxyl radical.

Question 93 Which immune cells deliberately produce ROS to kill bacteria?

Neutrophils.

Question 94 When is ROS generation especially increased clinically?

During reperfusion injury.

Question 95 How can ROS damage lipids?

By lipid peroxidation that disrupts cell membranes.

Question 96 How can ROS damage proteins?

By denaturing and precipitating proteins and other substrates.

Question 97 What enzyme converts superoxide in antioxidant defense?

Superoxide dismutase.

Question 98 What enzymes remove hydrogen peroxide in the handout figure?

Catalase and peroxidase.

Question 99 What type of inheritance is characteristic of mitochondrial DNA disorders?

Non-Mendelian maternal inheritance.

Question 100 Which tissues are most affected by mitochondrial DNA mutations?

Tissues with the greatest ATP requirements.