unit 2 week 2 pt 3

Question 1

Why are mitochondria often compared to power plants?

Answer 1

Like power plants, mitochondria extract energy from organic materials and store it as electrical energy. This energy is used to create an ionic gradient across the inner mitochondrial membrane, which can then be used to perform cellular work.

Question 2

How do ionic gradients function as a source of energy in cells?

Answer 2

An ionic gradient across a membrane is a form of stored energy that can be used for various functions: intestinal cells use it to transport sugars and amino acids; nerve cells use it to conduct neural impulses; mitochondria use it to synthesize ATP. Three key components are required: a system to generate the gradient, a membrane capable of maintaining the gradient, and machinery to use the gradient for work (e.g., ATP synthesis).

Question 3

What is oxidative phosphorylation, and how does it differ from substrate-level phosphorylation?

Answer 3

Oxidative phosphorylation synthesizes ATP using energy released from electrons during substrate oxidation in the mitochondria, making it the primary way cells produce ATP. In contrast, substrate-level phosphorylation forms ATP by the direct transfer of a phosphate group from a substrate molecule to ADP, occurring during glycolysis and the TCA cycle but producing significantly less ATP.
-diff explanation:
Oxidative phosphorylation (OP) generates ATP by using the energy from electron transport, while substrate-level phosphorylation (SLP) directly transfers a phosphate group from a substrate to ADP to form ATP. SLP is a direct transfer of a phosphate group from a high-energy substrate (like phosphoenolpyruvate or succinyl-CoA) to ADP, forming ATP.

Question 4

How significant is oxidative phosphorylation in ATP production?

Answer 4

It produces an estimated 2 × 10^26 molecules of ATP per day, which is over 60 kg of ATP in a human body, making oxidative phosphorylation the dominant ATP-generating process in most cells.

Question 5

Why is understanding oxidative phosphorylation important?

Answer 5

Discovering the mechanism of oxidative phosphorylation has been a major milestone in cell and molecular biology. Ongoing research continues to explore unanswered questions about how substrate oxidation releases free energy to power ATP synthesis.

Question 6

How are oxidizing agents ranked?

Answer 6

Oxidizing agents are ranked based on their affinity for electrons—the greater the affinity, the stronger the oxidizing agent.
-details:
-Oxidizing agents are ranked by their standard reduction potentials, with those having higher positive values being stronger oxidizing agents, meaning they have a greater tendency to gain electrons and be reduced.
-Standard Reduction Potential:
This value indicates the tendency of a substance to be reduced (gain electrons) under standard conditions.
Strong Oxidizing Agents:
Substances with high (positive) standard reduction potentials are strong oxidizing agents because they readily accept electrons and are easily reduced.
Weak Oxidizing Agents:
Substances with low (negative) standard reduction potentials are weak oxidizing agents because they have a lower tendency to gain electrons and are less easily reduced.

Question 7

How are reducing agents ranked?

Answer 7

Reducing agents are ranked based on their electron transfer potential—the lower the affinity for electrons (i.e., the more easily electrons are released), the stronger the reducing agent.
-details:
-Reducing agents are ranked by their standard reduction potentials, with stronger reducing agents having more negative potentials, indicating a greater tendency to lose electrons and be oxidized.

Question 8

What is an example of a strong reducing agent?

Answer 8

NADH is a strong reducing agent because it has a high electron transfer potential.

Question 9

What is an example of a weak reducing agent?

Answer 9

H2O is a weak reducing agent because it has a low electron transfer potential.

Question 10

How do oxidizing and reducing agents relate in a couple?

Answer 10

Strong reducing agents are paired with weak oxidizing agents, and vice versa.

Question 11

Give an example of an oxidation-reduction couple.

Answer 11

The NAD+/NADH couple, where NAD+ is a weak oxidizing agent, and NADH is a strong reducing agent.

Question 12

What is an oxidation-reduction potential (redox potential)?

Answer 12

It is the measure of a substance’s affinity for electrons, detected as voltage relative to a standard couple.

Question 13

What is the standard couple used for redox potential measurements?

Answer 13

The hydrogen couple (H+/H2) is the standard, with an assigned redox potential of 0.00 V under standard conditions.

Question 14

What are the standard conditions for measuring redox potential?

Answer 14

1.0 M solute concentrations, 1 atm pressure for gases, and a temperature of 25°C.

Question 15

Why is the redox potential of hydrogen listed as -0.42 V instead of 0.00 V in biological systems?

Answer 15

This value is measured at pH 7.0 (10^-7 M H+), which is more physiologically relevant than the standard pH 0.0 condition.

Question 16

How are redox potential values assigned?

Answer 16

Couples with strong reducing agents (good electron donors) have more negative redox potentials. Couples with strong oxidizing agents (good electron acceptors) have more positive redox potentials.

Question 17

What is the standard redox potential (E°’) for the NAD+/NADH couple?

Answer 17

-0.32 V.

Question 18

How does acetaldehyde compare to NADH as a reducing agent?

Answer 18

Acetaldehyde is a stronger reducing agent than NADH, with a more negative redox potential (-0.58 V).

Question 19

How is the standard free-energy change (ΔG) related to redox potential?

Answer 19

ΔG = -nFΔE°, where n = number of electrons transferred, F = Faraday constant (23.063 kcal/V·mol), and ΔE° = difference in standard redox potential between two couples.
-more: they’re inverse!
If E° is positive, then ΔG° is negative, indicating a spontaneous reaction.
If E° is negative, then ΔG° is positive, indicating a non-spontaneous reaction.

Question 20

What is the ΔG for the oxidation of NADH by O2?

Answer 20

-52.6 kcal/mol.

Question 21

How does this free-energy change relate to ATP synthesis?

Answer 21

The energy released from NADH oxidation (-52.6 kcal/mol) is sufficient to drive ATP formation (ΔG = 7.3 kcal/mol) under cellular conditions.

Question 22

How is this energy transfer carried out in the mitochondrion?

Answer 22

Through a series of small, energy-releasing steps to optimize ATP synthesis.

Question 23

Which TCA cycle intermediates transfer electrons to NAD+?

Answer 23

Isocitrate, α-ketoglutarate, and malate, as they have highly negative redox potentials.

Question 24

Why does succinate oxidation require FAD instead of NAD+?

Answer 24

The succinate/fumarate couple has a more positive redox potential, requiring FAD, which has a greater electron affinity than NAD+.

Question 25

What role do dehydrogenases play in electron transport?

Answer 25

Dehydrogenases transfer pairs of electrons from substrates to coenzymes. Five out of nine reactions in the TCA cycle are catalyzed by dehydrogenases, generating NADH and FADH2.

Question 26

Where do NADH molecules go after being formed in the mitochondrial matrix?

Answer 26

NADH molecules dissociate from their respective dehydrogenases and bind to NADH dehydrogenase (Complex I), an integral protein in the inner mitochondrial membrane.

Question 27

What is unique about succinate dehydrogenase?

Answer 27

Succinate dehydrogenase (catalyzing the formation of FADH2) is the only enzyme of the TCA cycle embedded in the inner mitochondrial membrane and is also a part of Complex II in the electron transport chain.

Question 28

How are electrons transferred from NADH and FADH2?

Answer 28

Electrons from NADH and FADH2 enter the electron transport chain (ETC), which consists of specific electron carriers embedded in the inner mitochondrial membrane, ultimately reducing O2 to H2O and generating a proton gradient for ATP synthesis.

Question 29

What are the five types of membrane-bound electron carriers in the electron transport chain (ETC)?

Answer 29

Flavoproteins (contain FAD or FMN), cytochromes (contain heme prosthetic groups), copper atoms (found in a single protein complex), ubiquinone (Coenzyme Q, UQ) (a lipid-soluble molecule), and iron-sulfur proteins (contain iron linked to sulfide ions).

Question 30

What are flavoproteins, and what is their function?

Answer 30

Flavoproteins consist of a polypeptide bound to FAD or FMN, both derived from riboflavin. They accept and donate 2 protons (H+) and 2 electrons (e-). Major flavoproteins include NADH dehydrogenase (Complex I of ETC) and succinate dehydrogenase (Complex II of ETC, also part of the TCA cycle).

Question 31

How do cytochromes participate in electron transport?

Answer 31

Cytochromes are proteins containing heme prosthetic groups. The iron atom in the heme undergoes reversible oxidation between Fe3+ (oxidized) and Fe2+ (reduced) as it accepts or donates a single electron.

Question 32

What role do copper atoms play in the ETC?

Answer 32

Three copper atoms are found in a single protein complex in the inner mitochondrial membrane. They accept and donate single electrons, cycling between Cu2+ (oxidized) and Cu+ (reduced) states.

Question 33

What is ubiquinone (Coenzyme Q), and why is it important?

Answer 33

Ubiquinone (UQ or CoQ) is a lipid-soluble electron carrier with a long hydrophobic chain. It can accept and donate 2 electrons and 2 protons, existing in three states: fully oxidized (UQ), partially reduced radical form (UQ•-), and fully reduced (UQH2). It remains in the lipid bilayer and diffuses rapidly between electron transport complexes.

Question 34

What are iron-sulfur proteins, and how do they function in electron transport?

Answer 34

Iron-sulfur proteins contain iron atoms bound to sulfide ions, rather than heme. Common types of iron-sulfur centers include [2Fe-2S] clusters and [4Fe-4S] clusters, transferring a single electron despite containing multiple iron atoms.

Question 35

How is the sequence of electron carriers in the ETC determined?

Answer 35

Scientists used inhibitors (e.g., rotenone, antimycin A) to block electron transport at specific sites and measured oxidation states of carriers. Spectrophotometry was used to detect whether carriers were in their oxidized or reduced states.

Question 36

How do electrons travel between electron carriers?

Answer 36

Electron transfer depends on the redox potential difference between carriers. Electrons move 'downhill', losing energy at each step, ultimately reducing O2 to H2O, through special 'tunneling pathways' composed of covalent and hydrogen bonds.

Question 37

What are the four electron-transport complexes in the inner mitochondrial membrane?

Answer 37

The four electron-transport complexes are Complexes I, II, III, and IV, each with a distinct role in the oxidation pathway.

Question 38

What are the two electron carriers that are not part of these complexes?

Answer 38

Ubiquinone (coenzyme Q) and cytochrome c are mobile electron carriers that shuttle electrons between the complexes.

Question 39

Where are ubiquinone and cytochrome c located?

Answer 39

Ubiquinone is dissolved in the lipid bilayer, while cytochrome c is a soluble protein in the intermembrane space.

Question 40

What is the function of ubiquinone and cytochrome c?

Answer 40

They transport electrons between the large, relatively immobile electron-transport complexes within the mitochondrial membrane.

Question 41

How do electrons enter the respiratory chain?

Answer 41

Electrons from NADH enter through Complex I, which transfers them to ubiquinone, forming ubiquinol. Electrons from FADH2 enter through Complex II, which transfers them directly to ubiquinone, bypassing Complex I.

Question 42

Why does FADH2 bypass Complex I?

Answer 42

Complex I has a too negative redox potential to accept electrons from FADH2, so they are transferred directly to ubiquinone via Complex II.

Question 43

Which three complexes function as proton pumps?

Answer 43

Complexes I, III, and IV act as proton pumps, transferring protons across the inner mitochondrial membrane.

Question 44

What happens when electrons move through these complexes?

Answer 44

At three key sites, electron transfer releases free energy, which is used to pump protons from the mitochondrial matrix to the intermembrane space, creating a proton gradient.

Question 45

What is a proton conduction pathway (proton wire)?

Answer 45

It is a network of acidic residues, hydrogen-bonded residues, and trapped water molecules that allow H+ ions to 'hop' through a channel, facilitating proton movement.

Question 46

How does the proton gradient contribute to ATP synthesis?

Answer 46

The proton gradient created by Complexes I, III, and IV drives ATP synthesis by allowing protons to flow back through ATP synthase, generating ATP.

Question 47

How can the proton-pumping function of these complexes be demonstrated?

Answer 47

Each complex can be purified and incorporated into artificial lipid vesicles, where they can still accept electrons and pump protons across the vesicle membrane.

Question 48

How do bacterial electron-transport complexes differ from mammalian ones?

Answer 48

Bacterial complexes have fewer subunits. The additional subunits in mammalian complexes do not participate in electron transport but are thought to assist in regulation or assembly.

Question 49

How has the electron-transport process evolved?

Answer 49

Despite structural differences, the fundamental electron-transport mechanism has remained largely unchanged since its evolution in prokaryotic ancestors billions of years ago.

Question 50

What is the function of Complex I in the electron-transport chain?

Answer 50

Complex I catalyzes the transfer of electrons from NADH to ubiquinone (UQ), forming ubiquinol (UQH2), marking the gateway to the electron-transport chain.

Question 51

What is the structure of Complex I?

Answer 51

Complex I consists of two portions: a hydrophilic domain that projects into the matrix and a hydrophobic portion embedded in the membrane.

Question 52

What are the two main activities required for the electron-transport chain that Complex I carries out?

Answer 52

Complex I carries out electron transfer and proton translocation.

Question 53

Where do the components required for electron transfer reside in Complex I?

Answer 53

All the components required for electron transfer are located within the hydrophilic portion of Complex I.

Question 54

How does electron transfer occur in Complex I?

Answer 54

FMN-containing flavoprotein oxidizes NADH at the complex's tip. Electrons are transferred through seven iron-sulfur centers to a protein-bound ubiquinone near the membrane boundary.

Question 55

What happens during the electron transfer from NADH to ubiquinone?

Answer 55

The transfer of a pair of electrons from NADH to ubiquinone is thought to be accompanied by the movement of four protons from the matrix into the intermembrane space.

Question 56

How does Complex I translocate protons across the membrane?

Answer 56

The membrane-embedded domain of Complex I contains a long α-helix (HL), which is in contact with three discontinuous transmembrane helices. These helices form half channels that, when connected by polar amino acid side chains, create a pathway for proton translocation.

Question 57

What happens when electrons move to ubiquinone in Complex I?

Answer 57

The movement of electrons to ubiquinone causes a conformational change in the complex, which induces lateral movement of helix HL, leading to the tilting of transmembrane helices. This change alters the ionic environment of proton-transferring residues, promoting proton movement across the membrane.

Question 58

How is the mechanism of Complex I compared to a steam engine?

Answer 58

The mechanism of Complex I is compared to a steam engine, with helix HL acting as the piston that drives the movement of downstream elements in the proton translocation machinery.

Question 59

What causes a conformational change in Complex I?

Answer 59

The movement of electrons to ubiquinone causes a conformational change in the complex, which induces lateral movement of helix HL, leading to the tilting of transmembrane helices.

Question 60

What is the significance of Complex I dysfunction?

Answer 60

Dysfunction of Complex I has been linked to certain neurodegenerative disorders.

Question 61

What is the structure of Complex II?

Answer 61

Complex II consists of four polypeptides: two hydrophobic subunits that anchor the protein in the membrane and two hydrophilic subunits that comprise the TCA cycle enzyme, succinate dehydrogenase.

Question 62

What is the function of Complex II?

Answer 62

Complex II provides a pathway for feeding lower energy electrons from succinate to FAD to ubiquinone.

Question 63

How do electrons travel through Complex II?

Answer 63

Electrons from FADH2 at the enzyme catalytic site travel a 40 Å distance through three iron-sulfur clusters to ubiquinone.

Question 64

Does Complex II translocate protons?

Answer 64

No, electron transfer through Complex II is not accompanied by proton translocation.

Question 65

What is the role of the heme group in Complex II?

Answer 65

The heme group helps to attract escaped electrons, preventing the formation of harmful superoxide radicals.

Question 66

What is the function of Complex III?

Answer 66

Complex III catalyzes the transfer of electrons from ubiquinol to cytochrome c.

Question 67

How many protons are translocated by Complex III?

Answer 67

Four protons are translocated across the membrane for every pair of electrons transferred through Complex III.

Question 68

How does Complex III translocate protons?

Answer 68

Two protons are derived from ubiquinol entering the complex and two additional protons are removed from the matrix and translocated by a second molecule of ubiquinol.

Question 69

What are the components of Complex III?

Answer 69

Complex III contains three subunits with redox groups: cytochrome b with two heme b molecules, cytochrome c1, and iron-sulfur protein.

Question 70

What is unique about cytochrome b in Complex III?

Answer 70

Cytochrome b is the only subunit of Complex III encoded by a mitochondrial gene.

Question 71

What is the final step of electron transport?

Answer 71

The final step involves the transfer of electrons from reduced cytochrome c to oxygen, forming water.

Question 72

How many protons are translocated by Complex IV?

Answer 72

For every molecule of O2 reduced to H2O, eight protons are involved: four protons are consumed in the formation of two molecules of water and four protons are translocated across the membrane to the intermembrane space.

Question 73

How does Complex IV function as a redox-driven proton pump?

Answer 73

Cytochrome oxidase catalyzes the reduction of oxygen and simultaneously expels protons from the matrix, which is measured as a drop in surrounding pH.

Question 74

What is the role of cytochrome oxidase in proton movement?

Answer 74

Cytochrome oxidase drives proton movement through conformational changes caused by the energy released during electron transfer, leading to proton pumping across the inner mitochondrial membrane.

Question 75

How is oxygen reduced to water in Complex IV?

Answer 75

Electrons are transferred from cytochrome c to a bimetallic copper center (CuA), then to a heme (heme a3), which together catalyze the reduction of O2 to H2O.

Question 76

What is the challenge of reducing oxygen to water?

Answer 76

The process of reducing O2 to H2O requires four electrons and must occur efficiently to prevent the accidental release of partially reduced oxygen species, which could damage cellular macromolecules.

Question 77

What happens to protons during the reduction of oxygen?

Answer 77

Four protons are consumed in the formation of water and four protons are pumped across the membrane, contributing to the electrochemical gradient.

Question 78

How does the cytochrome oxidase structure contribute to proton translocation?

Answer 78

Researchers have identified potential proton conduits within cytochrome oxidase, but their precise role remains under investigation.