Chapter 20: Electron Transport Chain

Mitochondria

In eukaryotic cells, aerobic processes occur in the _____

Cytosol

In eukaryotic cells, glycolysis (anaerobic), occurs in the _____

NADH and FADH₂; O₂

ETC involves a series of intermediate carries that transfer electrons from _____ to _____

Inner mitochondrial membrane

ETC reactions take place in the _____

Oxidative phosphorylation

Process for generating ATP
→ depends on the creation of a pH gradient (proton gradient) within the mitochondrion as a result of electron transport

Proton gradient

Difference between the hydrogen ion (H+) concentrations in the mitochondrial matrix and that in the intermembrane space, which is the basis of coupling between oxidation and phosphorylation

Oxidative phosphorylation in ETC

Bulk of ATP produced in the system occurs in _____

Oxidized; Reduced

In ETC, NADH and FADH₂ are _____, and O₂ is _____

Proton gradient

• Created by electron transport from one carrier to another

• Coupled to the production of ATP in aerobic metabolism

I, III, IV

Which complex has proton pumping ability?

Reduced

Molecule with a high reduction potential tends to be _____ if it is paired with a molecule with a lower reduction potential

Higher

Electron flow favors ____ reduction potential

NADH-CoQ oxidoreductase

Enzyme for Complex I

NADH-CoQ oxidoreductase

Catalyzes the transfer of electrons from NADH to CoQ

• Integral part of the inner mitochondrial membrane

• Includes several proteins that contain an iron-sulfur cluster and the flavoprotein that oxidizes NADH

  • Flavoprotein has a flavin coenzyme called flavin mononucleotide (FMN)

Flavoprotein

Involved in Complex I and II; oxidizes NADH

Flavin mononucleotide (FMN)

Flavin coenzyme of flavoprotein that can accept and pass on electrons

Hydroquinone

Reduced form of quinone

Succinate-coenzyme Q oxidoreductase

Enzyme for Complex II

Succinate-coenzyme Q oxidoreductase

Catalyzes the transfer of electrons from succinate to CoQ

Cytochromes

Groups of heme-containing proteins in the ETC
→ In each heme group, the iron is successively reduced to Fe(II) and reoxidized to Fe(III)

Cytochromes

When CoQ is reoxidized, electrons are passed to _____

Side chain

All cytochromes contain a heme group; what differentiates them from one another?

CoQH2-cytochrome c oxidoreductase

Enzyme for Complex III

CoQH₂-cytochrome c oxidoreductase

Catalyzes the oxidation of reduced CoQ (CoQH₂)

2

How many molecules of cytochrome c are required for every molecule of coenzyme Q?

Q cycle

• Provides the link between two-electron transfers and one-electron transfers

• Involves the flow of electrons via a cyclic path from CoQH2 to other components of the complex

• Depends on the fact that coenzyme Q can exist in three forms

• One electron is passed from CoQH2 to the iron–sulfur clusters to cytochrome c1, leaving coenzyme Q in the semiquinone form

• Provides a mechanism for electrons to be transferred one at a time from coenzyme Q to cytochrome c1

• Complex III results in proton pumping and supplies enough energy to drive ATP production because of the reaction that it catalyzes

Semiquinone

A partially reduced form of coenzyme Q (CoQ) that occurs when it gains one electron

Semiquinone form

After one electron is passed from CoQH₂ to the iron-sufur clusters to cytochrome c1, CoQH₂ turns into _____

Cytochrome c oxidase

Enzyme for Complex IV

Cytochrome c oxidase

Catalyzes the transfer of electrons from cytochrome c to O₂

Complex IV

Contains cytochromes a and a₃, as well as two Cu²⁺ ions that are involved in electron transport

Cu²⁺ ions

Intermediate electron acceptors that lie between cytochromes a and a₃ in the following sequence:

Iron

The _____ of the heme group is involved in a series of redox reactions

Sulfur

Nonheme iron proteins contain _____

• Iron is usually bound to cysteine or to S₂^-

Voltage gradient

Differences in the concentration of ions across the membrane generate a _____

Energy-releasing oxidation reactions

Give rise to proton pumping and a pH gradient across the inner mitochondrial membrane, which is used to drive the phosphorylation of ADP

Coupling process

Converts the energy of the electrochemical potential (voltage drop) across the membrane to the chemical energy of ATP

Coupling factor

Needed to link oxidation and phosphorylation

ATP synthase (mitochondrial ATPase)

Complex protein oligomer that is responsible for the production of ATP in the mitochondria

F₀

Portion of ATP synthase

• Spans the membrane (Integral)

• Consists of 3 different kinds of polypeptide chains (a, b, c)

F₁

Portion of ATP synthase

• Projects into the matrix

• Consists of 5 different kinds of polypeptide chain in the ratio α₃β₃γδε

• Site of ATP synthesis

Uncouplers

• Inhibit the phosphorylation of ADP without affecting electron transport

• Reduce oxygen to H₂O but do not enable the production of ATP

• Examples

  • 2,4-dinitrophenol

  • Valinomycin

  • Gramicidin A

P/O Ratio

Ratio of ATP produced by oxidative phosphorylation to oxygen atoms consumed in electron transport

2.5 ATP

P/O = _____ ATP when NADH is oxidized

1.5 ATP

P/O = _____ ATP when FADH₂ is oxidized

Chemiosmotic coupling

Mechanism of coupling that requires a proton gradient across the inner mitochondrial membrane

matrix; intermembrane space

Proteins that serve as electron carriers take up protons from the _____ when they are reduced and release them to the _____ when they are reoxidized

NADH, CoQ, O₂

Reactions of _____, _____, _____ require protons

F₀

Protons flow back into the matrix through channels in the _____ unit of ATP synthase

F₁

Flow of protons is accompanied by formation of ATP, which takes place in the _____

Conformational coupling

• Proton gradient leads to conformational changes in a number of proteins, including ATP synthase

• There are three sites for substrate on ATP synthase and three possible conformational states

Open (O)

Conformational site on ATP Synthase

• Low affinity for substrate

Loose-binding (L)

Conformational site on ATP Synthase

• Not catalytically active

• ADP and P_i bind at a site in this conformational

Tight-binding (T)

Conformational site on ATP Synthase

• Catalytically active

• ATP is bound at a site in this conformation

T to O

This transition occurs when the tightly bound ATP is released

L to T

This transition happens when the loosely bound substrates (ADP and inorganic phosphate) are converted into tightly bound ATP

Shuttle mechanisms

Transport metabolites between the mitochondria and the cytosol

Glycerol-phosphate shuttle

Mechanism for transferring electrons from NADH in the cytosol to FADH2 in the mitochondrion

Reduction of DHAP

How is glycerol phosphate produced?

FADH₂

Product of the glycerol-phosphate shuttle mechanism, which passes electrons through the electron transport chain

Glycerol-phosphate shuttle

NADH is oxidized to NAD⁺, and FAD is reduced to FADH₂

Malate-aspartate shuttle

• Found in mammalian kidney, liver, and heart

• Uses the fact that malate can cross the mitochondrial membrane, while oxaloacetate cannot

• Transfer of electrons from NADH in the cytosol produces NADH in the mitochondrion

Cytosolic malate dehydrogenase

Oxaloacetate is reduced to malate by _____

Cytosol

• Oxaloacetate is reduced to malate by cytosolic malate dehydrogenase

• Cytosolic NADH is oxidized to NAD+

• Aspartate is converted to oxaloacetate in the cytosol

Mitochondrion

• Conversion of malate back to oxaloacetate is catalyzed by mitochondrial malate dehydrogenase

• Oxaloacetate is converted to aspartate, which can cross the mitochondrial membrane

Mitochondrial malate dehydrogenase

Conversion of malate back to oxaloacetate is catalyzed by _____

30 (glycerol) or 32 (malate)

Total ATP produced when:

• Pyruvate generated from glycolysis can enter the citric acid cycle

• NADH and FADH₂ molecules that result from the citric acid cycle are reoxidized through the electron transport chain