Lecture 1 Flashcards
1
Q
Chemiosmotic theory
A
Explanation of how the proton circuitry in the inner membrane of the mitochondria serves as the driving force to generate ATP
2
Q
Who proposed the chemiosmotic theory
A
Dr. Peter Mitchell
3
Q
Pathways of ATP generation
A
O2 independent and O2 dependent
4
Q
O2 independent pathway of ATP generation
A
Glycolysis
5
Q
When is the O2 independent pathway of ATP generation used
A
When energy is required in the absence of oxygen
6
Q
Molecule broken down in glycolysis
A
Glucose
7
Q
How is glucose split in glycolysis
A
Using energy provided by 2 ATPs
8
Q
Net production of ATP from glycolysis
A
2 ATP molecules for each glucose molecule that is broken down
9
Q
Main product of glycolysis
A
2 molecules of pyruvate
10
Q
Where does pyruvate go after glycolysis
A
Shuttled into the mitochondrion via specific carriers for further breakdown
11
Q
Where does glycolysis occur
A
Cytoplasm
12
Q
What happens to pyruvate in the mitochondria
A
Goes through the krebs cycle
13
Q
Another name for the krebs cycle
A
Citric acid cycle
14
Q
What molecule starts off the krebs cycle besides pyruvate
A
acetyl-co-A
15
Q
Does the krebs cycle require oxygen
A
No
16
Q
O2 dependent pathways of ATP generation
A
Electron transport system (ETS) and oxidative phosphorylation (OXPHOS)
17
Q
Where do the electron transport system and oxidative phosphorylation occur
A
Mitochondrial level
18
Q
Electron transport system
A
System involving the movement of electrons across proteins
19
Q
Electron terminal acceptor in the electron transport system
A
Oxygen
20
Q
Leading cause of mitochondrial dysfunction
A
Deficiencies in electron transport system proteins
21
Q
Oxidative phosphorylation
A
Specialized proteins phosphorylate ADP to form ADP
22
Q
What produces more molecules of ATP? Glycolysis (O2 independent) or O2 dependent pathways
A
O2 dependent pathways inside the mitochondria
23
Q
Another name for oxygen dependent ATP production
A
Aerobic ATP production
24
Q
Where does oxygen dependent ATP production occur
A
Mitochondria
25
Is ATP generated from the krebs cycle
NO
26
What is generated from the krebs cycle
Reducing agents
27
What happens to pyruvate in the krebs cycle
Decarboxylated (loses a carbon atom)
28
__ is produced in the krebs cycle from a series of decarboxylitic reactions
CO2
29
Types of reducing agents produced in the krebs cycle
NADH and FADH
30
Role of reducing agents
Donate electrons to very specific enzymes and proteins
31
What does the electron transport system use reducing agents for
To shuttle electrons
32
Reducing agents are needed to power up ___
Proton pumps
33
What do electrons flow across in the electron transport system
Inner membrane and enzyme complexes
34
What is generated when the electrons in the electron transport system flow across the inner membrane of the mitochondria
Electrochemical gradient
35
Result of the generation of an electrochemical gradient in the electron transport system
Proteins that span across the inner membrane will react to electrons flowing across the membrane and H+ protons will be pumped across
36
Where are H+ ions pumped to and from in the electron transport system
Pumped from inside the mitochondria to the intermembrane space
37
Electrochemical gradient is used by ___ to generate ATP
F0 F1 ATP synthase
38
Do the outer and inner membranes have the same proteins
No
39
Which membrane has a higher surface area: outer or inner
Inner
40
Phospholipid bilayer head
Glycerol
41
Phospholipid bilayer tail
Fatty acid
42
Products in the membrane come from ___
Citric acid cycle
43
Products in the membrane
NADH2 and FADH2
44
What will reducing agents in the membrane do during the electron transport system
Donate electrons
45
___ shuttle electrons across and will move down the pathway
A series of enzyme complexes
46
Enzyme complexes that shuttle electrons
I, III, IV
47
Electron flow causes net movement of ___ across the membrane
Protons
48
What does the change in membrane protein conformation lead to
Net pumping of protons from the matrix to the intermembrane space
49
What do electrons become bound to as they continue flowing
Oxygen
50
What is oxygen taken up by in the electron transport system
Complex IV
51
What does complex IV oxidase use oxygen to do
Put together electrons and 2 H+ to form water
52
Electron transport is coupled to the ____
Proton pumping action
53
Changes of conformation of the complexes leads to
Proton pumping action
54
Where are protons pumped
Intermembrane space
55
What is the result of protons being pumped into the intermembrane space
At some point, you will have a lower concentration of protons in the matrix and a higher concentration of protons in the intermembrane space
56
Electrochemical gradient
Difference in concentration of protons between matrix and intramembrane space
57
What is the use of electrochemical gradient
Can be used to perform useful work for the cell
58
What does ATP synthase use the electrochemical gradient for
To channel protos across the membrane back into the matric and perform useful work (ATP formation)
59
What besides the electrochemical gradient moves protons across the membrane
Uncoupling proteins
60
How many types of uncoupling proteins are there in human mitochondria
3
61
Why did people originally think that uncoupling proteins were only found in endotherms
Because they generate heat
62
How much heat do uncoupling proteins generate
30%
63
How do uncoupling proteins work
Uncouple by channeling protons across the membrane without making ATP
64
How is ATP moved out of the mitochondria
Specialized nucleotide translocators in the membrane
65
When did bioenergetics emerge
1950s
66
Bioenergetics was a quest to describe the mechanisms of ___
Substrate oxidation and coupling of energy between substrate oxidation and ATP production
67
Who described respiratory states and associated enzymes (relation between oxygen consumption and substrate oxidation)
Chance and Williams
68
Substrate that can be added to the mitochondria to produce FADH2
Succinate
69
What happens when succinate is added to the mitochondria and FADH2 is produced
The electron transport system is activated
70
Why does ADP need to be present in the electron transport system
Needed for ATPase to work
71
1 respiratory state
Just mitochondria and no substrates
72
3 respiratory state
ADP added
73
4 respiratory state
Respiration
74
5 respiratory state
Oxygen is depleted
75
Why are limited substrates added to mitochondria in the lab
To assess mitochondrial function by monitoring oxygen consumption
76
What did Dr. Peter Mitchell propose
A mechanism of energy coupling via proton cycling and ATPase function
77
What did Dr. Peter Mitchell say that substrates can fuel ATP production through
Chemiosmotic proton circuit
78
What is the respiratory chain responsible for
Channeling electrons
79
What is a proton circuit capable of generating
Electrochemical gradient
80
What were the debates again Dr. Peter Mitchell's theory called
Oxphos wars
81
Other names of electrochemical force generated from the movement of protons across the membrane
Hypertonic potential or proton motive force
82
Proteins pump protons from ___ to ____
Inner matrix
| Intermembrane space
83
What does the proton motive force drive
Production of ATP
84
How does proton motive force drive the production of ATP
Protons flow back across the ATPase to produce ATP in the presence of ADP and inorganic phosphate
85
___ accepts electrons and binds oxygen and hydrogen to them to form water
Cytochrome C
86
Oxygen interacts with ___
electrons
87
The formation of water leads to...
a gradient that is utilized by F0 F1 ATPase
88
What are mitochondria the product of
Endosymbiosis
89
How were mitochondria formed by endosymbiosis
Ancient eukaryotic cell engulfed smaller prokaryotic cells with the capacity for oxidative phosphorylation
90
By engulfing smaller cells with the capacity for oxidative phosphorylation, the bigger cell can now generate energy under ___ conditions
Aerobic
91
Most of the components of the inner mitochondrial membrane are shared with ___
Bacterial inner membrane
92
___ are the key in the chemiosmotic theory
Proton pumps
93
Types of proton pumps
Primary and secondary
94
What are primary pumps mostly in charge of
Producing a proton gradient (H+ particularly)
95
Which pump develops and drives the proton motor force
Primary
96
Another name for secondary pumps
ATPase
97
Secondary pumps are dependent on the function of ___
Primary pumps
98
ATPase proton translocation is ___
reversible (can work backwards)
99
Secondary pumps create
Massive gradient
100
Massive gradient generated by secondary pumps
Lots of protons in the intermembrane space compared with the matrix
101
What does the gradient do to ATPase
Causes it to work backwards
102
ATP synthesis depends on ___
Proton translocation
103
What happens to the pH as protons are pumped across the membrane
Slight drop in the pH of the intermembrane space (becomes more acidic)
104
How much of a pH drop is normal in the intermembrane space
0.5 pH units
105
Oxidative phosphorylation
Formation of ATP by ATPase
106
What does oxidative phosphorylation depend on
Electrochemical gradient
107
Proton circuit is analog to
Electrical circuit
108
Rate of chemical conversion depends on ___
Electron flow
109
Both electrical and proton circuits can be ___
Shorted
110
Work
Channel protons across the ATPase to produce ATP
111
Other ways to dissipate gradient to let protons across
- uncoupling protein
| - chemicals act as proton carriers or poke holes in the inner membrane to transport protons back to the matric
112
Another word for uncoupling
Short circuit
113
What is uncoupled by uncoupling proteins
Proton motive generating forces from ATP generating forces (O2 consumption from ATP production)
114
Which membrane is more porous: outer or inner
Outer
115
VDAC
(voltage dependent anionic channel) is a protein responsible for shuttling ions across the outer membrane
116
How is VDAC opened
Always open, no change in voltage needed
117
Inner membrane is composed of __% integral (transmembrane) proteins
50%
118
What is similar between the prokaryote inner membrane and mitochondrial inner membrane
Cardiolipin
119
Cristae morphology changes with ___ and ___
Tissue type and sample processing
120
What does the complex cristae resemble
Meshwork
121
Shape of mitochondria
Highly variable
122
Cation
Positive
123
Anion
Negative
124
What membranes are involved in ion transport
All membranes (inner and outer)
125
How many modalities of ion movement are there
Four
126
Are modalities of ion movement energy dependent
Some are
127
K+ at a higher ___ concentration
Intercellular
128
Na+ at a higher ___ concentration
Extracellular
129
Modes of ion movement across membranes
- Bilayer mediated
- Protein mediated
- Passive
- Coupled to metabolism
130
Bilayer mediated transport is the common composition of ___
Energy conserving membranes
131
Natural permeability
Ions freely move across from high to low concentration
132
Is energy needed for natural permeability
No, it is passive
133
What is protein mediated transport catalyzed by
Integral, membrane-spanning proteins
134
Type of proteins involved in protein mediated transport
Uncoupling
135
What can protein mediated transport be fueled by
ATP
136
Example of protein mediated transport
Ca2+ pumps, Na2+ pumps
137
Direction of ion flow in protein mediated transport
Can be against the concentration gradient (low to high)
138
Passive ion transport
Driven by concentration or electrical gradients
139
Coupled to metabolism ion transport: active or passive
Active
140
Example of coupled to metabolism ion transport
Ion pumps
141
Two types of ion transport
- Number of ions and direction of transport
| - Charge movement across the membrane
142
Number of ions and direction of transport
Transport process can involve a single ion or tightly coupled transport of two or more species
143
Uniport
Protein mediated transport across the membrane of a single ion from high to low concentration
144
Symport
One ion carried from high to low and another ion carried alone the line (movement is forced even if it is going across the concentration gradient)
145
Antiport
Ions move across the membrane in different directions (example: Na+/K+ pump > Na+ out and K+ in)
146
Charge movement across the membrane
Electroneutral if transport of uncharged particles or antiport of ions of opposite charges
147
Electroneutral
No net change in charges (electrochemical potential of the membrane is maintained)
148
Electrical
Leads to changes in the membrane potential (transport of charges leads to uneven distribution)
149
Ionophores
Chemicals or compounds that can alter membrane permeability
150
Membrane permeability
How permeable membrane is to a particular ion
151
Ionophores that carry charge but not protons
Valinomycin
152
Valinomycin
Natural antibiotic from streptomyces
153
How does valinomycin carry positive charge across the inner membrane
Creating interactions between cations
154
What is valinomycin highly selective towards
K+
155
Ions lose ___ when they bind to ionophore
Water or hydration
156
Ionophores that carry proton but not charge
Nigericin
157
Nigericin
Form a structure similar to valinomycin
158
Nigericin ions
Neutral exchange of K+ for H+
159
Where is K+ located
Intermembrane space
160
Ionophores that carry protons and charge
Protonophores
161
Example of protonophore
FCCP
162
Are protonophores electroneutral
No
163
What are protonophores used for in the lab
Change the permeability of the membrane to H+
164
How do protonophores make the membrane more permeable to H+
Poke selective holes in the inner membrane for H+ to move from high to low concentration
165
Result of cycling across the membrane by protonophores
Catalyze the net electrical uniport of protons and increase the proton conductance of the membrane
166
What is the results of increasing the proton conductance of the membrane
The proton circuit is short-circuited, allowing the process of delta p generation (proton motive force) to be uncoupled from ATP synthesis
167
Protonophores act as ___
Uncouplers
168
What do protonophores uncouple
Proton pumping action from ATP production
