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

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2
Q

Who proposed the chemiosmotic theory

A

Dr. Peter Mitchell

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3
Q

Pathways of ATP generation

A

O2 independent and O2 dependent

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4
Q

O2 independent pathway of ATP generation

A

Glycolysis

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5
Q

When is the O2 independent pathway of ATP generation used

A

When energy is required in the absence of oxygen

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6
Q

Molecule broken down in glycolysis

A

Glucose

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7
Q

How is glucose split in glycolysis

A

Using energy provided by 2 ATPs

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8
Q

Net production of ATP from glycolysis

A

2 ATP molecules for each glucose molecule that is broken down

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9
Q

Main product of glycolysis

A

2 molecules of pyruvate

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10
Q

Where does pyruvate go after glycolysis

A

Shuttled into the mitochondrion via specific carriers for further breakdown

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11
Q

Where does glycolysis occur

A

Cytoplasm

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12
Q

What happens to pyruvate in the mitochondria

A

Goes through the krebs cycle

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13
Q

Another name for the krebs cycle

A

Citric acid cycle

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14
Q

What molecule starts off the krebs cycle besides pyruvate

A

acetyl-co-A

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15
Q

Does the krebs cycle require oxygen

A

No

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16
Q

O2 dependent pathways of ATP generation

A

Electron transport system (ETS) and oxidative phosphorylation (OXPHOS)

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17
Q

Where do the electron transport system and oxidative phosphorylation occur

A

Mitochondrial level

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18
Q

Electron transport system

A

System involving the movement of electrons across proteins

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19
Q

Electron terminal acceptor in the electron transport system

A

Oxygen

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20
Q

Leading cause of mitochondrial dysfunction

A

Deficiencies in electron transport system proteins

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21
Q

Oxidative phosphorylation

A

Specialized proteins phosphorylate ADP to form ADP

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22
Q

What produces more molecules of ATP? Glycolysis (O2 independent) or O2 dependent pathways

A

O2 dependent pathways inside the mitochondria

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23
Q

Another name for oxygen dependent ATP production

A

Aerobic ATP production

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24
Q

Where does oxygen dependent ATP production occur

A

Mitochondria

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25
Q

Is ATP generated from the krebs cycle

A

NO

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26
Q

What is generated from the krebs cycle

A

Reducing agents

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27
Q

What happens to pyruvate in the krebs cycle

A

Decarboxylated (loses a carbon atom)

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28
Q

__ is produced in the krebs cycle from a series of decarboxylitic reactions

A

CO2

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29
Q

Types of reducing agents produced in the krebs cycle

A

NADH and FADH

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30
Q

Role of reducing agents

A

Donate electrons to very specific enzymes and proteins

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31
Q

What does the electron transport system use reducing agents for

A

To shuttle electrons

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32
Q

Reducing agents are needed to power up ___

A

Proton pumps

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33
Q

What do electrons flow across in the electron transport system

A

Inner membrane and enzyme complexes

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34
Q

What is generated when the electrons in the electron transport system flow across the inner membrane of the mitochondria

A

Electrochemical gradient

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35
Q

Result of the generation of an electrochemical gradient in the electron transport system

A

Proteins that span across the inner membrane will react to electrons flowing across the membrane and H+ protons will be pumped across

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36
Q

Where are H+ ions pumped to and from in the electron transport system

A

Pumped from inside the mitochondria to the intermembrane space

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37
Q

Electrochemical gradient is used by ___ to generate ATP

A

F0 F1 ATP synthase

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38
Q

Do the outer and inner membranes have the same proteins

A

No

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39
Q

Which membrane has a higher surface area: outer or inner

A

Inner

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40
Q

Phospholipid bilayer head

A

Glycerol

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41
Q

Phospholipid bilayer tail

A

Fatty acid

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42
Q

Products in the membrane come from ___

A

Citric acid cycle

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43
Q

Products in the membrane

A

NADH2 and FADH2

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44
Q

What will reducing agents in the membrane do during the electron transport system

A

Donate electrons

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45
Q

___ shuttle electrons across and will move down the pathway

A

A series of enzyme complexes

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46
Q

Enzyme complexes that shuttle electrons

A

I, III, IV

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47
Q

Electron flow causes net movement of ___ across the membrane

A

Protons

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48
Q

What does the change in membrane protein conformation lead to

A

Net pumping of protons from the matrix to the intermembrane space

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49
Q

What do electrons become bound to as they continue flowing

A

Oxygen

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50
Q

What is oxygen taken up by in the electron transport system

A

Complex IV

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51
Q

What does complex IV oxidase use oxygen to do

A

Put together electrons and 2 H+ to form water

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52
Q

Electron transport is coupled to the ____

A

Proton pumping action

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53
Q

Changes of conformation of the complexes leads to

A

Proton pumping action

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54
Q

Where are protons pumped

A

Intermembrane space

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55
Q

What is the result of protons being pumped into the intermembrane space

A

At some point, you will have a lower concentration of protons in the matrix and a higher concentration of protons in the intermembrane space

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56
Q

Electrochemical gradient

A

Difference in concentration of protons between matrix and intramembrane space

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57
Q

What is the use of electrochemical gradient

A

Can be used to perform useful work for the cell

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58
Q

What does ATP synthase use the electrochemical gradient for

A

To channel protos across the membrane back into the matric and perform useful work (ATP formation)

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59
Q

What besides the electrochemical gradient moves protons across the membrane

A

Uncoupling proteins

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60
Q

How many types of uncoupling proteins are there in human mitochondria

A

3

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61
Q

Why did people originally think that uncoupling proteins were only found in endotherms

A

Because they generate heat

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62
Q

How much heat do uncoupling proteins generate

A

30%

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63
Q

How do uncoupling proteins work

A

Uncouple by channeling protons across the membrane without making ATP

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64
Q

How is ATP moved out of the mitochondria

A

Specialized nucleotide translocators in the membrane

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65
Q

When did bioenergetics emerge

A

1950s

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66
Q

Bioenergetics was a quest to describe the mechanisms of ___

A

Substrate oxidation and coupling of energy between substrate oxidation and ATP production

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67
Q

Who described respiratory states and associated enzymes (relation between oxygen consumption and substrate oxidation)

A

Chance and Williams

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68
Q

Substrate that can be added to the mitochondria to produce FADH2

A

Succinate

69
Q

What happens when succinate is added to the mitochondria and FADH2 is produced

A

The electron transport system is activated

70
Q

Why does ADP need to be present in the electron transport system

A

Needed for ATPase to work

71
Q

1 respiratory state

A

Just mitochondria and no substrates

72
Q

3 respiratory state

A

ADP added

73
Q

4 respiratory state

A

Respiration

74
Q

5 respiratory state

A

Oxygen is depleted

75
Q

Why are limited substrates added to mitochondria in the lab

A

To assess mitochondrial function by monitoring oxygen consumption

76
Q

What did Dr. Peter Mitchell propose

A

A mechanism of energy coupling via proton cycling and ATPase function

77
Q

What did Dr. Peter Mitchell say that substrates can fuel ATP production through

A

Chemiosmotic proton circuit

78
Q

What is the respiratory chain responsible for

A

Channeling electrons

79
Q

What is a proton circuit capable of generating

A

Electrochemical gradient

80
Q

What were the debates again Dr. Peter Mitchell’s theory called

A

Oxphos wars

81
Q

Other names of electrochemical force generated from the movement of protons across the membrane

A

Hypertonic potential or proton motive force

82
Q

Proteins pump protons from ___ to ____

A

Inner matrix

Intermembrane space

83
Q

What does the proton motive force drive

A

Production of ATP

84
Q

How does proton motive force drive the production of ATP

A

Protons flow back across the ATPase to produce ATP in the presence of ADP and inorganic phosphate

85
Q

___ accepts electrons and binds oxygen and hydrogen to them to form water

A

Cytochrome C

86
Q

Oxygen interacts with ___

A

electrons

87
Q

The formation of water leads to…

A

a gradient that is utilized by F0 F1 ATPase

88
Q

What are mitochondria the product of

A

Endosymbiosis

89
Q

How were mitochondria formed by endosymbiosis

A

Ancient eukaryotic cell engulfed smaller prokaryotic cells with the capacity for oxidative phosphorylation

90
Q

By engulfing smaller cells with the capacity for oxidative phosphorylation, the bigger cell can now generate energy under ___ conditions

A

Aerobic

91
Q

Most of the components of the inner mitochondrial membrane are shared with ___

A

Bacterial inner membrane

92
Q

___ are the key in the chemiosmotic theory

A

Proton pumps

93
Q

Types of proton pumps

A

Primary and secondary

94
Q

What are primary pumps mostly in charge of

A

Producing a proton gradient (H+ particularly)

95
Q

Which pump develops and drives the proton motor force

A

Primary

96
Q

Another name for secondary pumps

A

ATPase

97
Q

Secondary pumps are dependent on the function of ___

A

Primary pumps

98
Q

ATPase proton translocation is ___

A

reversible (can work backwards)

99
Q

Secondary pumps create

A

Massive gradient

100
Q

Massive gradient generated by secondary pumps

A

Lots of protons in the intermembrane space compared with the matrix

101
Q

What does the gradient do to ATPase

A

Causes it to work backwards

102
Q

ATP synthesis depends on ___

A

Proton translocation

103
Q

What happens to the pH as protons are pumped across the membrane

A

Slight drop in the pH of the intermembrane space (becomes more acidic)

104
Q

How much of a pH drop is normal in the intermembrane space

A

0.5 pH units

105
Q

Oxidative phosphorylation

A

Formation of ATP by ATPase

106
Q

What does oxidative phosphorylation depend on

A

Electrochemical gradient

107
Q

Proton circuit is analog to

A

Electrical circuit

108
Q

Rate of chemical conversion depends on ___

A

Electron flow

109
Q

Both electrical and proton circuits can be ___

A

Shorted

110
Q

Work

A

Channel protons across the ATPase to produce ATP

111
Q

Other ways to dissipate gradient to let protons across

A
  • uncoupling protein

- chemicals act as proton carriers or poke holes in the inner membrane to transport protons back to the matric

112
Q

Another word for uncoupling

A

Short circuit

113
Q

What is uncoupled by uncoupling proteins

A

Proton motive generating forces from ATP generating forces (O2 consumption from ATP production)

114
Q

Which membrane is more porous: outer or inner

A

Outer

115
Q

VDAC

A

(voltage dependent anionic channel) is a protein responsible for shuttling ions across the outer membrane

116
Q

How is VDAC opened

A

Always open, no change in voltage needed

117
Q

Inner membrane is composed of __% integral (transmembrane) proteins

A

50%

118
Q

What is similar between the prokaryote inner membrane and mitochondrial inner membrane

A

Cardiolipin

119
Q

Cristae morphology changes with ___ and ___

A

Tissue type and sample processing

120
Q

What does the complex cristae resemble

A

Meshwork

121
Q

Shape of mitochondria

A

Highly variable

122
Q

Cation

A

Positive

123
Q

Anion

A

Negative

124
Q

What membranes are involved in ion transport

A

All membranes (inner and outer)

125
Q

How many modalities of ion movement are there

A

Four

126
Q

Are modalities of ion movement energy dependent

A

Some are

127
Q

K+ at a higher ___ concentration

A

Intercellular

128
Q

Na+ at a higher ___ concentration

A

Extracellular

129
Q

Modes of ion movement across membranes

A
  • Bilayer mediated
  • Protein mediated
  • Passive
  • Coupled to metabolism
130
Q

Bilayer mediated transport is the common composition of ___

A

Energy conserving membranes

131
Q

Natural permeability

A

Ions freely move across from high to low concentration

132
Q

Is energy needed for natural permeability

A

No, it is passive

133
Q

What is protein mediated transport catalyzed by

A

Integral, membrane-spanning proteins

134
Q

Type of proteins involved in protein mediated transport

A

Uncoupling

135
Q

What can protein mediated transport be fueled by

A

ATP

136
Q

Example of protein mediated transport

A

Ca2+ pumps, Na2+ pumps

137
Q

Direction of ion flow in protein mediated transport

A

Can be against the concentration gradient (low to high)

138
Q

Passive ion transport

A

Driven by concentration or electrical gradients

139
Q

Coupled to metabolism ion transport: active or passive

A

Active

140
Q

Example of coupled to metabolism ion transport

A

Ion pumps

141
Q

Two types of ion transport

A
  • Number of ions and direction of transport

- Charge movement across the membrane

142
Q

Number of ions and direction of transport

A

Transport process can involve a single ion or tightly coupled transport of two or more species

143
Q

Uniport

A

Protein mediated transport across the membrane of a single ion from high to low concentration

144
Q

Symport

A

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
Q

Antiport

A

Ions move across the membrane in different directions (example: Na+/K+ pump > Na+ out and K+ in)

146
Q

Charge movement across the membrane

A

Electroneutral if transport of uncharged particles or antiport of ions of opposite charges

147
Q

Electroneutral

A

No net change in charges (electrochemical potential of the membrane is maintained)

148
Q

Electrical

A

Leads to changes in the membrane potential (transport of charges leads to uneven distribution)

149
Q

Ionophores

A

Chemicals or compounds that can alter membrane permeability

150
Q

Membrane permeability

A

How permeable membrane is to a particular ion

151
Q

Ionophores that carry charge but not protons

A

Valinomycin

152
Q

Valinomycin

A

Natural antibiotic from streptomyces

153
Q

How does valinomycin carry positive charge across the inner membrane

A

Creating interactions between cations

154
Q

What is valinomycin highly selective towards

A

K+

155
Q

Ions lose ___ when they bind to ionophore

A

Water or hydration

156
Q

Ionophores that carry proton but not charge

A

Nigericin

157
Q

Nigericin

A

Form a structure similar to valinomycin

158
Q

Nigericin ions

A

Neutral exchange of K+ for H+

159
Q

Where is K+ located

A

Intermembrane space

160
Q

Ionophores that carry protons and charge

A

Protonophores

161
Q

Example of protonophore

A

FCCP

162
Q

Are protonophores electroneutral

A

No

163
Q

What are protonophores used for in the lab

A

Change the permeability of the membrane to H+

164
Q

How do protonophores make the membrane more permeable to H+

A

Poke selective holes in the inner membrane for H+ to move from high to low concentration

165
Q

Result of cycling across the membrane by protonophores

A

Catalyze the net electrical uniport of protons and increase the proton conductance of the membrane

166
Q

What is the results of increasing the proton conductance of the membrane

A

The proton circuit is short-circuited, allowing the process of delta p generation (proton motive force) to be uncoupled from ATP synthesis

167
Q

Protonophores act as ___

A

Uncouplers

168
Q

What do protonophores uncouple

A

Proton pumping action from ATP production