Chapter 18- Oxidative Phosphorylation Flashcards
(135 cards)
1
Q
What is the purpose of oxidative phosphorylation?
A
There is a large disparity between the amount of ATP molecules we have and the amount of ATP we need. Each ATP molecule is recycled 300 times per day, and oxidative phosphorylation is the process that accomplishes this recycling.
2
Q
Electron transport chain/respiratory chain
A
4 large protein complexes embedded in the mitochondrial membrane. This is where the flow of electrons from NADH and FADH2 to oxygen takes place.
3
Q
What is the energy released by the electron transport chain used for?
A
Three of the complexes of the ETC use the energy released by the electron flow to pump protons out of the mitochondrial matrix. The unequal distribution of protons creates a pH gradient and a transmembrane electrical potential that will eventually be essential for the synthesis of ATP.
4
Q
Proton-motive force
A
A force created by the unequal distribution of protons from the ETC. Protons flow back to the mitochondrial matrix through an enzyme complex to synthesize ATP.
5
Q
Which molecules are used in oxidative phosphorylation?
A
ADP is phosphorylated, and uses one proton (H+) to produce ATP and water
6
Q
The oxidation of fuels and the phosphorylation of ADP are coupled by
A
A proton gradient across the inner mitochondrial membrane
7
Q
Cellular respiration
A
The generation of high transfer potential electrons by the citric acid cycle. their flow through the respiratory chain, and the accompanying synthesis of ATP. Uses an inorganic compound (like oxygen) to serve as an oxygen acceptor, and an organic or inorganic compound as an oxygen donor.
8
Q
Which two processes are referred to an cellular respiration collectively?
A
Oxidative phosphorylation and the citric acid cycle
9
Q
Where does the electron transport chain and ATP synthesis occur?
A
Mitochondria
10
Q
Where does the citric acid cycle occur?
A
Mitochondrial matrix
11
Q
2 compartments in the mitochondria
A
- Intermembrane space between the outer and inner membranes
2. Matrix- bounded by the inner membrane
12
Q
Cristae
A
The inner membrane of the mitochondria is folded into ridges called cristae. The cristae increase the surface area in the inner mitochondrial membrane, which creates more sites for oxidative phosphorylation
13
Q
Outer membrane of the mitochondria
A
Very permeable to most small molecules and ions, since it contains a protein called mitochondrial porin (VDAC)
14
Q
Mitochondrial porin (VDAC)
A
This the most prevalent protein in the outer mitochondrial membrane. It plays a role in the regulated flux of anionic species like phosphate. chloride, and adenine nucleotides across the outer membrane.
15
Q
Inner mitochondrial membrane permeability
A
Impermeable to nearly all ions and polar molecules. A family of transporters shuttles metabolites like ATP, pyruvate, and citrate across the inner mitochondrial membrane.
16
Q
2 faces of the inner mitochondrial membrane
A
- Matrix side/N side- negatively charged
2. Cytoplasmic side/P side- positively charged and freely accessible to most small molecules in the cytoplasm
17
Q
Mitochondria endosymbiotic relationship
A
Mitochondria live in an endosymbiotic relationship with the host cell. They contain their own DNA, which codes for proteins. However, the mitochondria contains many proteins encoded by nuclear DNA. Cells that contain mitochondria depend on the organelles for oxidative phosphorylation, and the mitochondria depend on the cell for their existence.
18
Q
How many base pairs does human mitochondria have?
A
16,569 base pairs. It encodes 13 respiratory chain proteins as well as small and large ribosomal RNAs and enough tRNAs to translate all codons.
19
Q
How did the endosymbiotic event of mitochondria occur?
A
It’s thought to have occurred when a free living organism capable of oxidative phosphorylation was engulfed by another cell. Sequence data suggest that all mitochondria are descendants of an ancestor of Rickettsia prowazekii, which was engulfed by another cell
20
Q
Which features of the mitochondria suggest an endosymbiotic event?
A
The double membrane, circular DNA, and mitochondrial specific transcription and translation machinery.
21
Q
Which organism does the evidence of an endosymbiotic event come from?
A
It comes from examination of the most bacteria-like mitochondrial genome- from the protozoan Reclinomonas americana. The genome of R. americana encodes less than 2% of the protein-encoding genes of E. coli. That means that 2% of bacterial genes are found in all mitochondria. This suggests that the mitochondrial genomes became part of the nuclear genome, so the original bacterial cell lost DNA and was incapable of independent living, and the host cell become dependent on the ATP generated by the mitochondria.
22
Q
Electron transfer potential vs phosphoryl transfer potential
A
In oxidative phosphorylation, the electron transfer potential of NADH or FADH2 is converted into the phosphoryl transfer potential of ATP.
23
Q
E0
A
The reduction potential E0, or redox potential, is the measure of a molecule’s tendency to donate or accept electrons. A strong reducing agent readily donates electrons and has a negative E0, while a strong oxidizing agent readily accepts electrons and has a positive E0.
24
Q
What do the n and f mean in the standard free energy change?
A
n is the number of electrons transferred and F is the Faraday constant.
25
How is redox potential measured?
A experiment is conducted where a sample half cell is connected through an agar bridge to a standard reference half cell. Electrons flow through the wire connecting the cells, while ions flow through the agar bridge. Electrons flow from the sample half cell to the standard reference half cell. The reduction potential of the X (oxidant) is the observed voltage at the start of the experiment.
26
What does it mean for a molecule to have a positive or negative reduction potential?
A strong reducing agent (like NADH) is poised to donate electrons and has a negative reduction potential, while a strong oxidizing agent (like oxygen) is ready to accept electrons and has a positive reduction potential.
27
What is the driving force of oxidative phosphorylation?
The electron transfer potential of NADH or FADH2 relative to that of oxygen. The energy released by the reduction of oxygen with NADH2 is initially used to generate a proton gradient that is then used for the synthesis of ATP and the transport of metabolites across the mitochondrial membrane.
28
Free energy value
ΔG° can be calculated to have a value of −220.1 kJ mol−1 (−52.6 kcal mol−1)
29
3 protein complexes embedded in the mitochondrial membrane
1. NADH-Q oxidoreductase (complex 1)
2. Q-cytochrome c oxidoreductase (complex 3)
3. Cytochrome c oxidase (complex 4)
30
Function of the protein complexes in the mitochondrial membrane?
Electrons are transferred from NADH to oxygen through the chain of protein complexes. Electron flow within the complexes releases a lot of energy and powers the transport of protons across the inner mitochondrial membrane.
31
Succinate Q-reductase
A fourth large protein complex (complex 2) that contains the succinate dehydrogenase that generates FADH2 in the citric acid cycle. In contrast with the other complexes, this complex does not pump electrons
32
Where do the electrons from succinate Q-reductase go next?
Electrons from this FADH2 enter the electron transport chain at Q-cytochrome c oxidoreductase.
33
Complexes 1, 3, and 4 are associated in
A supramolecular complex which facilitates the rapid transfer of substrate and prevents the release of reaction intermediates.
34
Electron carriers that bring electrons from one complex to the next (2)
1. Coenzyme Q
| 2. Cytochrome c oxidase
35
Coenzyme Q (ubiquinone) function
An electron carrier that is a hydrophobic quinone. It diffuses rapidly within the inner mitochondrial membrane. Electrons are carried from NADH-Q oxidoreductase to Q cytochrome c oxidoreductase (complex 3) by the reduced form of Q. Electrons from the FADH2 generated by the citric acid cycle are transferred first to coenzyme Q and then to complex 3
36
Coenzyme Q structure
Coenzyme Q is a quinone derivative with a long tail consisting of 5 carbon isoprene units that account for its hydrophobic nature. The number of isoprene units in the tail depends on the species. The most common form in mammals contains 10 isoprene units
37
Oxidation states of coenzyme Q
Quinones can exist in several oxidation states. In the fully oxidized state (Q), coenzyme Q has two keto groups. The addition of one electron and one proton results in the semiquinone form. For quinones, electron transfer reactions are coupled to proton binding and release. This property is key to transmembrane proton transport.
38
Semiquinone
The addition of one electron and one proton results in a semiquinone. The semiquinone can lose a proton to form a semiquinone radical anion (Q-).
39
Ubiquinol
Formed by the addition of a second electron and proton to the semiquinone. Ubiquinol has the formula (QH2), and is the full reduced form of coenzyme Q, which holds its protons more tightly.
40
Q pool
Because ubiquinone is soluble in the membrane, a pool of Q and QH2 (the Q pool) is thought to exist in the inner mitochondrial membrane, although it may be confined to the protein complexes of the electron transport chain.
41
Cytochrome C electron carrier
A small soluble protein that shuttles electrons from complex 3 to complex 4. In general, cytochromes are electron-transferring proteins that contain a heme prosthetic group. The heme iron cycles
between Fe2+ and Fe3+ as it accepts or donates electrons
42
Iron-sulfur proteins
Also called nonheme iron proteins- prominent electron carriers. These proteins contain various types of iron–sulfur clusters. Like cytochromes, the iron cycles between Fe2+ and Fe3+ as it accepts or donates electrons
43
Frataxin
Frataxin is a small mitochondrial protein that is crucial for the synthesis of Fe-S clusters. Deficiency in frataxin results in Friedreich’s ataxia, which affects the nervous system as well as the heart and skeletal systems. The most common mutation is trinucleotide expansion
44
Where do the electrons of NADH enter the respiratory chain?
At NADH-Q oxidoreductase (aka complex 1).
45
Structure of complex 1/NADH dehydrogenase
This is a large enzyme that acts as a proton pump. It is encoded by genes residing in both the mitochondria and the nucleus. Complex 1 is L shaped, with a horizontal arm lying in the membrane and a vertical arm that projects into the matrix.
46
After electrons from NADH enter the chain, what happens? (3)
1. The electrons from NADH are passed along to Q to form QH2 by Complex I.
2. QH2 leaves the enzyme for the Q pool in the hydrophobic interior of the inner mitochondrial membrane
3. Four protons are simultaneously pumped out of the mitochondrial matrix by Complex I.
47
Electron carriers between NADH and Q
The electron carriers between NADH and Q include flavin mononucleotide (FMN) and several iron–sulfur proteins.
48
Where does FADH2 enter the electron transport chain?
At the second protein complex
49
When is FADH2 formed?
In the citric acid cycle, in the oxidation of succinate to fumarate by succinate dehydrogenase. Succinate dehydrogenase is part of complex 2, and FADH2 doesn't leave the complex. Its electrons are transferred to Fe-S centers and then to Q to form QH2, which is used to move electrons further down the electron transport chain.
50
Succinate-Q reductase complex (Complex II)
Complex 2, in contrast with NADH-Q oxidoreductase, does not pump protons from one side of the membrane to the other. This means that less ATP is formed from the oxidation of FADH2 than from NADH.
51
What happens to the ubiquinol generated by complexes 1 and 2?
The electrons from QH2 are passed on to cytochrome c by complex 3. The flow of a pair of electrons through this complex leads to the effective net transport of 2 hydrogen to the intermembrane space. This is half the yield obtained with NADH-Q reductase because of a smaller thermodynamic driving force.
52
Cytochrome
An electron transferring protein that contains a heme prosthetic group.
53
Cytochromes in complex 3 (2)
1. b
| 2. C1
54
Rieske center
In addition to the hemes, cytochromes contain an iron-sulfur protein with a 2Fe-2S center. This is unusual because one of the iron ions is coordinated by two histidine residues rather than two cysteine residues. This coordination stabilizes the center in its reduced form, raising its reduction potential so that it can readily accept electrons from QH2.
55
What is the function of the Q cycle?
To funnel electrons from a two electron carrier to a one electron carrier and pump protons. QH2 passes two electrons to Q-cytochrome c oxidoreductase. However, cytochrome c is an acceptor of electrons in this complex and can only accept one electron.
56
Q cycle
The mechanism for the coupling of electron transfer from Q to cytochrome c to transmembrane proton transport. Two QH2 molecules bind to the complex consecutively, each giving up two electrons and two hydrogens. These protons are released to the intermembrane space. The first QH2 to exit the Q pool binds to the first Q binding site, and its two electrons travel through the complex to different destinations.
57
What happens to the first electron in the Q cycle?
One electron flows to the Rieske 2Fe-2S cluster, then to cytochrome c1, then to a molecule of oxidized cytochrome c, converting it to its reduced form. The reduced cytochrome c molecule can diffuse away from the enzyme to continue down the respiratory chain.
58
What happens to the second electron in the Q cycle?
It passes through the two heme groups of cytochrome b to an oxidized ubiquinone in a second Q binding site. The Q in the second binding site is reduced to a semiquinone radical anion by the electron from the first QH2. The now fully oxidized Q leaves the first Q site, free to re-enter the Q pool. Cytochrome c is also reduced.
59
Cytochrome c oxidase (complex 4) function
Complex 4 catalyzes the transfer of electrons from the reduced form of cytochrome c to molecular oxygen, the final acceptor.
60
What is the reason that organisms require oxygen?
The reaction that complex 4 catalyzes is aerobic (requires oxygen)
61
Which molecules are used in the complex 4 reaction?
Cytochrome c oxidase accepts four electrons from four molecules of cytochrome c in order to catalyze the reduction of O2 to two molecules of H2O
62
What occurs during the complex 4 reaction?
In the cytochrome c oxidase reaction, eight protons are removed from the matrix. Four protons, called chemical protons, are used to reduce oxygen. In addition, four protons are pumped into the intermembrane space
63
Structure of complex 4
It consists of 13 subunits, 3 of which are encoded by the mitochondrial genome. Cytochrome c oxidase contains 2 heme A groups and 3 copper ions arranged in copper centers, designated A and B.
64
Copper A center of cytochrome c oxidase
This center contains 2 copper ions linked by two bridging cysteine residues. This center initially accepts electrons from reduced cytochrome c.
65
Copper B center of cytochrome c oxidase
Bonded to 3 histidine residues, one of which is modified by covalent linkage to a tyrosine residue. The copper centers alternate between the reduced and oxidized forms as they accept and donate electrons
66
Flow of two electrons in cytochrome c oxidase
Cytochrome c- CuA/CuA- heme a- heme a3- CuB
67
When the Fe of heme a3 and CuB are reduced
They bind oxygen as a peroxide bridge between them. The addition of two more electrons and four protons generates two molecules of water.
68
Respirasome definition
The large complex formed by 3 of the components of the electron transport chain
69
Respirasome structure
Consists of 2 copies of complex 1, complex 3, and complex 4. The respirasome forms a circular structure, with the copies of complex 1 and 4 surrounding complex 3. Two copies of cytochrome c are located on the surface of complex 3. This structure allows for complex 2 to associate in a gap between complexes 1 and 4. This is also another example of multienzyme pathways that are organized into large complexes to enhance efficiency.
70
Reactive oxygen species
Partial reduction of O2 generates highly reactive oxygen derivatives, called reactive oxygen species (ROS). ROS are implicated in many pathological conditions. When oxygen is reduced fully with two electrons, it makes a safe product (water). When only one electron is used, toxic products result.
71
Examples of ROS (3)
Superoxide ion, peroxide ion, and hydroxyl radical (OH-).
72
What are some examples of pathological conditions that might include free radical injury? (6)
1. Emphysema, bronchitis
2. Parkinson Disease
3. Cervical cancer
4. Cerebrovascular disorders, ischemia
5. Duchenne muscular dystrophy
6. Down syndrome
73
Superoxide dismutase (SOD)
An enzyme that protects against oxidative damage by ROS. It scavenges superoxide radicals by catalyzing the conversion of two of these radicals into hydrogen peroxide and molecular oxygen.
74
Two forms of SOD
Eukaryotes express two forms of this enzyme, a manganese-containing mitochondrial form and a copper-and-zinc-dependent cytoplasmic form. Both enzymes have a similar mechanism.
75
Catalase
The hydrogen peroxide formed by superoxide dismutase and by other processes is scavenged by catalase. This is a ubiquitous heme protein that catalyzes the dismutation of hydrogen peroxide into water and molecular oxygen.
76
What is a benefit of exercise?
Increases the amount of SOD in the cell, since elevated aerobic metabolism causes more ROS to be generated. More protective enzymes are synthesized as a result. This has a net protective effect because SOD more effectively protects the cell even during periods of rest.
77
What are some benefits of ROS?
The controlled generation of these molecules can be important for signal transduction pathways. Growth factors increase ROS as part of their signaling pathway. ROS have been implicated in the control of cell differentiation, immune response, autophagy, and other metabolic activities.
78
How are electrons transferred between electron-carrying groups of the respiratory chain?
Frequently, electron carrying groups are not in direct contact with each other. Electrons can move through space, even through a vacuum. However, the protein environment provides a more efficient pathway for electron conduction. For groups in contact, these reactions can be very fast.
79
The rate of electron transfer through space falls rapidly when
The electron donor and electron acceptor move apart from each other.
80
How has the conformation of cytochrome c changed over time?
Cytochrome c is a highly conserved protein, which has remained almost constant over time. Cytochrome c from any eukaryotic species will react in vitro with the cytochrome c oxidase from any other species. Examination of the primary structure of cytochrome c from a variety of species allowed the construction of phylogenetic trees.
81
Proton motive force consists of (2)
A chemical gradient (pH gradient) and a charge gradient. The charge gradient is created by the positive charge on the unequally distributed protons forming the chemical gradient.
82
What powers ADP rephosphorylation?
A proton gradient. The oxidation of NADH is very exergonic, and is coupled to the synthesis of ATP, which is endergonic. This means that there is a net release of energy. This generates a proton motive force that helps to synthesize ATP.
83
ATP synthase
Aka complex 5. It is an enzyme complex in the inner mitochondrial membrane that carries out the synthesis of ATP.
84
How is the oxidation of NADH coupled to the phosphorylation of ADP?
A mechanism is suggested by the chemiosmotic hypothesis (Mitchell)
85
Chemiosmotic hypothesis
Suggests that electron transport and ATP synthesis are coupled by a proton gradient across the inner mitochondrial membrane. The transfer of electrons through the respiratory chain leads to the pumping of protons from the matrix to the intermembrane space. The hydrogen concentration becomes lower in the matrix, and protons flow back into the matrix to equalize the distribution. This flow of protons drives the synthesis of ATP by ATP synthase.
86
How was the chemiosmotic hypothesis tested?
Bacteriorhodopsin (a membrane proton from bacteria that pumps protons when illuminated) played the role of the respiratory chain. Synthetic vesicles containing bacteriorhodopsin and mitochondrial ATP synthase were created. When the vesicles were exposed to light, ATP was formed. This experiment showed that the respiratory chain and ATP synthase are biochemically separate systems that are linked only by a proton-motive force.
87
2 components of ATP synthase
1. F0- a "stick" part embedded in the inner mitochondrial membrane
2. F1- protrudes into the mitochondrial matrix and contains the proton channel/catalytic activity of the synthase
88
F1 structure
Contains the three active sites, located on the three β subunits. Also contains 5 polypeptide chains
89
Y subunit of ATP synthase
Connects the F1 and F0 components, although they are also connected by an exterior column.
90
Beta subunits of ATP synthase
Each β subunit is distinct in that each subunit interacts differently with the γ subunit.
91
How do ATP synthases interact with each other?
They interact to form dimers. This association stabilizes the individual enzymes to the rotational forces required for catalysis and facilitates the curvature of the inner mitochondrial membrane. Formation of the curves (cristae) facilitates ATP synthase
92
ATP synthase catalyzes which reaction?
The formation of ATP from ADP and orthophosphate (HPO4).
93
What must happen for ATP and ADP to function as substrates?
They must bind to Mg +2 to function as substrates
94
What occurs during the ATP synthase reaction?
A terminal oxygen atom of ADP attacks the phosphorus atom of Pi to form a pentacovalent intermediate, which then dissociates into ATP and water.
95
How does the flow of protons drive the synthesis of ATP?
Enzyme bound ATP forms readily in the absence of a proton-motive force. However, ATP does not leave the catalytic site unless protons flow through the enzyme. Therefore, the role of the proton gradient is not to form ATP but to release it from the synthase.
96
How do the 3 active sites of ATP synthase respond to the flow of protons?
A binding change mechanism for proton driven ATP synthesis occurs. A beta subunit can perform each of 3 sequential steps in the synthesis of ATP by changing conformation.
97
3 conformations of the beta subunit
1. In the O (open) form, nucleotides can bind to or be released from the β subunit.
2. In the L (loose) form, nucleotides are trapped in the β subunit.
3. In the T (tight) form, ATP is synthesized from ADP and Pi in the absence of a proton gradient but cannot be released from the enzyme
98
Steps of the binding change mechanism (3)
1. ADP and Pi binding
2. ATP synthesis
3. ATP release
99
What causes the interconversion between the conformations of the beta subunits?
The movement of the γ subunit in response to proton flow powers the interconversion of the forms. Each subunit cycles through the three conformations, but no two subunits are ever in the same conformation
100
Is it possible to observe the proposed rotation of ATP synthase directly?
It is possible to observe the rotation of the γ subunit directly. Cloned α3β3γ subunits were attached to a glass slide that allowed the movement of the γ subunit to be visualized as a result of ATP hydrolysis. The hydrolysis of a single ATP powered the rotation of
the γ subunit 120°.
101
Through what region of ATP synthase does proton flow occur?
F0 component
102
How does proton flow occur through the Y subunit of ATP synthase?
The mechanism depends on the structures of the a and c subunits of F0.
103
Subunit a of ATP synthase
Subunit a, which abuts the c ring, has two channels that reach halfway into the a subunit. One half-channel opens to the intermembrane space and the other to the matrix
104
C rings of ATP synthase
Protons enter the half-channel facing the proton-rich intermembrane space, bind to a glutamate or aspartate residue on one of the subunits of the c ring, and then leave the c subunit once it rotates around to face the matrix half-channel. The force of the proton gradient powers rotation of the c ring. The rotation of the c rings powers the movement of the γ subunit, which in turn alters the conformation of the β subunits.
105
What do ATP synthase and G proteins have in common?
ATP synthase and the Gα subunit of heterotrimeric G proteins are members of the P-loop NTPase family of proteins. They do not exchange nucleotides unless they are stimulated to do so by interaction with other proteins.
106
How is exchange between the cytoplasm and the mitochondria mediated?
By membrane-spanning transporter proteins
107
How is cytoplasmic NADH reoxidized to NAD+ under aerobic conditions?
The respiratory chain must use NAD+ for glycolysis, but NADH can't pass into the mitochondria for oxidation by the respiratory chain because the inner mitochondrial membrane is impermeable to NAD+ and NADH. Solution- electrons from NADH rather than NADH itself are carried across the mitochondrial membrane, and can be introduced to the electron transport chain through the glycerol 3-phopshate shuttle.
108
Glycerol 3-phopshate shuttle
This is a means of introducing electrons from NADH into the ETC.
109
Glycerol 3-phosphate shuttle first step
The first step is the transfer of a pair of electrons from NADH to the intermediate dihydroxyacetone phosphate to form glycerol 3-phosphate.
110
Which enzyme catalyzes the glycerol 3-phosphate shuttle?
Glycerol 3-phosphate dehydrogenase in the cytoplasm
111
What occurs in the second step of the glycerol 3-phopshate shuttle?
An electron pair from glycerol 3-phosphate is transferred to an FAD prosthetic group in the dehydrogenase enzyme to form FADH2. Dihydroxyacetone phosphate is also regenerated.
112
Why is FAD used as the electron acceptor in the glycerol 3-phopshate shuttle?
This enables electrons from cytoplasmic NADH to be transported into the mitochondria against an NADH concentration gradient. This uses one molecule of ATP per two electrons, resulting in only 1.5 molecules of ATP produced. This is prominent in muscle and allows for a high rate of oxidative phosphorylation
113
Malate aspartate shuttle
In heart and liver, electrons from cytoplasmic NADH are used to generate mitochondrial NADH in the malate-aspartate shuttle. The malate-aspartate shuttle consists of two membrane transporters and four enzymes.
114
How are highly charged ATP and ADP molecules moved across the inner mitochondrial membrane into the cytoplasm?
A transport protein (antiporter) called ATP-ADP translocase. It enables these molecules to transverse the permeability barrier. The flow of ATP and ADP are coupled, so ADP enters the mitochondrial matrix only if ATP exits and vice versa. Neither ATP nor ADP is bound to Mg2+.
115
How much energy does the exchange of ATP and ADP require?
The ATP-ADP exchange is energetically expensive. Approximately 25% of the proton-motive force generated by the respiratory chain is consumed by this exchange process.
116
Structures of mitochondrial transporters for metabolites
They have a common tripartite structure. The ATP-ADP translocase is composed of three tandem repeats of a 100-amino acid domain, with each domain containing two transmembrane segments. In addition to the translocase, the inner mitochondrial membrane has many transporters, or carriers, to enable the exchange of ions or charged molecules between the mitochondrial matrix and cytoplasm.
117
What determines the rate of respiratory pathways?
The ATP needs of the cell
118
Out of all the molecules of ATP formed by combustion of glucose, how many are formed during oxidative phosphorylation?
Of the approximately 30 molecules of ATP formed by the complete combustion of glucose, 26 are formed in oxidative phosphorylation. The metabolism of glucose to two molecules of pyruvate in glycolysis yields the remaining four ATP.
119
How many ATP are produced when glucose is fermented?
When glucose undergoes fermentation, only two
| molecules of ATP are generated per glucose molecule.
120
Respiratory (acceptor) control
Electrons do not flow through the electron-transport chain unless ADP is available to be converted into ATP. The regulation of oxidative phosphorylation by ADP is called respiratory (or acceptor) control. Respiratory control is an example of control of
metabolism by energy charge
121
How does ADP added affect the amount of oxygen consumed?
As more ADP is added, more oxygen is consumed. As the supply of ADP is exhausted, oxygen consumption levels off.
122
Inhibitory factor 1 (IF1)
A conserved protein that inhibits the hydrolytic ability of ATP synthase. IF1 is believed to prevent ATP hydrolysis when oxygen is not available to accept the electron of the electron transport chain. Overexpression of IF1 in some cancers facilitates the induction of aerobic glycolysis
123
Nonshivering thermogenesis definition
If electron transport is uncoupled from ATP synthesis, heat is
generated, a process called nonshivering thermogenesis
124
What facilitates non shivering thermogenesis?
Such uncoupling is facilitated in a regulated fashion by uncoupling protein 1 (UCP-1; also called thermogenin), an integral protein of the inner mitochondria membrane
125
Where does non shivering thermogenesis occur?
Adult humans display nonshivering thermogenesis, which occurs in brown adipose tissue (BAT). BAT is very rich in mitochondria, and uncoupling occurs here. Obesity leads to a decrease in BAT- the homologs UCP-2 and UCP-3 also play a role in energy homeostasis and may also be important in regulation of body weight.
126
UCP-1 in pigs
As pigs evolved, they lost the ability to express UCP-1. They do not undergo non shivering thermogenesis and must use other means to retain heat (e.g., nesting, large litter size, and shivering). In pig farming, infant mortality is high, even when using heat lamps to warm the newborns; the artificial heating cost is also significant. Use of a technique (CRISPR) to insert the UCP-1 back into this mammal’s genome have been successful
127
How can poisons inhibit oxidative phosphorylation? (4 ways)
1. Inhibition of the electron-transport chain by preventing generation of the proton-motive force
2. Inhibition of ATP synthase
3. Uncoupling of electron-transport chain function from ATP synthesis. 2,4-dinitrophenol is an example of this; it carries protons across the inner mitochondrial membrane down their concentration gradient, bypassing ATP synthase.
4. Inhibition of the ATP export
128
Disruption of what complex is the most common cause of mitochondrial disease?
Disruption of Complex I is the most common cause of mitochondrial disease. Defects in the components of the electron-transport chain not only reduce ATP synthesis but also increase the amount of reactive oxygen species formed, leading to increased mitochondrial damage
129
Apoptosis
Programmed cell death (or apoptosis) results in selective cell death. Programmed cell death is crucial for tissue remodeling during development and for the removal of damaged cells. Mitochondria can control the process of programmed cell death
130
How does the mitochondria control apoptosis?
During the process, the outer mitochondrial membrane becomes highly permeable. Cytochrome c, upon leaving the mitochondria, activates the death pathway
131
What is the significance of proton gradients?
Proton gradients power a wide array of biological processes in all organisms. They are considered to be a central, interconvertible
currency of free energy within living organisms.
132
Leber hereditary optic neuropathy (LHON)
Leber hereditary optic neuropathy (LHON) is a form of vision
loss due to death of optic neurons. It is due to mutations in the mitochondrial genes that encode Complex I (e.g., one that causes a Pro -> Lys substitution). A mouse with this mutation was made to allow the resulting phenotype to be further studied
133
LHON mouse study
Mitochondria in the optic nerve of these LHON mice were found to be abnormal in shape and higher in number, matching what is observed in human LHON patients. Mitochondria from LHON mice were isolated and studied to determine whether the LHON phenotype results from a decrease in ATP production or an increase in ROS-induced damage
134
What did researchers learn from studying mice with LHON? (4)
1. Complex I in the LHON mice functioned only 70% as well as
it did in the control mice; this was due to decreased function,
not decreased complex amount.
2. This reduced Complex I function indeed has a corresponding
impact on the ability of the electron transport chain to reduce
O2.
3. The LHON mice release higher amounts of a major ROS,
hydrogen peroxide (H2O2), which can cause oxidative
damage to cells.
4. The ability to produce ATP is not impacted in LHON mice
135
What conclusion could researchers draw from the LHON mouse studies?
These results, at least for the Pro -> Lys mutation, support the
idea that ROS production may be the main cause of damage in
LHON
