Mitochondria Bioenergetics Flashcards

(125 cards)

1
Q

In glycolysis, we made 2 ATP, 2 NADH and 2 pyruvate. What must be do next?

A

We need to remake NAD+.

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2
Q

Before we begin the TCA cycle, what do we want to do?

A

Convert 3 carbon pyruvate to 2 carbon acetyl group part of acetyl coA.

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3
Q

When we converted pyruvate to a 2 carbon acetyl group part of acetyl coA, what happened to the carbon?

A

Pyruvate was decarboxylized by the PDC and it was lost as CO2

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4
Q

What is responsible for a majority of carb, protein and fat oxidation?

A

The TCA cycle

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5
Q

What are we doing in the TCA cycle?

A

oxidizing carbon so that we can harness the NRG.

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6
Q

Is the TCA cycle anabolic, catabolic or amphibolic?

A

Amphibolic

Both catabolism and anabolism will occur. Remember, its a cycle.
We have to build up and build down.

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7
Q

Where does the TCA cycle occur?

A

Mitochondrial matrix

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8
Q

3 stages of TCA cycle

A
  1. Break down carbs, fats and proteins
  2. Convert the breakdown products into acetyl co-A
  3. Allow acetyl co-A to enter the TCA cycle
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9
Q

Products of the TCA cycle are

A

3 NADHs,
1 FADH2
1 GTP

And 2 CO2s are released.

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10
Q

Why is the TCA cycle important?

A

it is the driver of cellular respiration. It takes acetyl coA and harvest energy in the form of NADH, FADH2 and ATP. The reduced electron carriers are then taken to the ETC and though oxidative phosphorylation, generate most of the ATP we use!

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11
Q

Acetyl co-A is a activated form of _______ and can be made from three sources:

what sources and how

A

acetate.
Acetyl coA can be made from

  1. Carbs
    Glucose–> pyruvate via oxidation
    Pyruvate–> Acetyl CoA via decarboxylation
  2. Fats
    TAGS–> FA–> acetyl CoA via B oxidation
  3. Proteins
    AA are converted to acetyl CoA
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12
Q

In acetyl coA, where is the high NRG bond?

A

thioester bond

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13
Q

Pyruvate is made in the cytosol but the TCA cycle occurs in the mitochondrial matrix.
how does pyruvate enter the mitochondria?

A

Pyruvate will enter the MT matrix using a MPC (mitochondrial pyruvate carrier)

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14
Q

How do we convert pyruvate to acetyl coA?

A

Pyruvate is converted to acetyl CoA through the PDC.
The PDC will decarboxylize pyruvate in a series of reactions to create acetyl coA.

2 NADHs are made and a CO2 is released

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15
Q

When is the PDC inactive?

A

PDC is inactive when it is phosphorylated.

Thus, the PDC is always phosphorylated to make sure that it is not always on and we are not always going through the TCA cycle.

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16
Q

How do we ensure that we are not always going through the Krebs cycle?

A

the PDC is always phosphorylated, making it INACTIVE.

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17
Q

So the PDC is active when it is

A

dephosphorylated

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18
Q

What happens when we have a shit ton of pyruvate, but our body is deficient in phosphotases?

A

If we are deficient in phosphotases, our PDC cannot be dephosphorylated, which means it cannot be turned on.

Pyruvte must utilize another method: lactic acid will be made INSTEAD of acetyl coA

Thus, people who have a buildup of pyruvate but lack phosphotases will often get LACTIC ACID BUILDUP!

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19
Q

What should people who have a lot of pyruvate, but little phosphotases becareful of?

A

They should avoid to further build up of pyruvate. thus, they should avoid ALANINE because alanine is converted to pyruvate.

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20
Q

In a high NRG state, do we want to keep the pyruvate system going fast?

A

No. It should run smoothly. So, if we are in a high NRG state we want it to slow down.

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21
Q

Inhibitors of PDC

A

NADH
ATP
Acetyl CoA

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22
Q

Activators of PDC

A

Pyruvate and

ADP

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23
Q

If we are in a low energy state, what do we do with the TCA cycle?

A

We need NRG we so want to upregulate it.

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24
Q

aerobic respiration is coupled with ______

A

OxPhos

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25
__ steps in the TCA cycle
8
26
1st step in the TCA cycle
[OAA+ acetyl coA]--> citrate via citrate synthase Co-A is kicked off. This is a irreversible regulatory step.
27
2nd step
citrate-->isocitrate
28
3rd step
[isocitrate--> alpha keto glutarate] via isocitrate DH. Isocitrate DH is the rate limiting step. NAD+ is reduced to NADH CO2 is lost
29
4th step
[alpha ketoglutarate--> succinyl coA] via alpha keta glutrate DH REgulated step NAD+ is reduced to NADH CO2 is lost
30
5th step
[succinyl co-A]--> succinate via succinate thiokinase GTP is made
31
6th step
[Succinate--> fumarate] Succinate DH FADH2 is made
32
7th step
fumarate--> malate
33
8th
Malate--> OAA via malate DH 3rd and final NADPH is a made
34
What are the 3 regulated, irreversible steps?
1. Citrate synthase 2. Isocitrate DH 3. Alpha keto glutarate DH
35
Where is NADH made?
3 NADHs are made. ``` 1. isocitrate DH CO2 is also lost 2. alphaketo glutarate DH CO2 is also lost 3. Malate DH ```
36
What is the rate limiting step?
Isocitrate DH, when isocitrate--> alpha ketoglutarate.
37
Where is our GTP made
GTP is made by succinyl thiokinase succinyl co-A--> succinate
38
Where is FADH2 made?
Succinate--> fumarate
39
When ATP levels are low, the TCA cycle is ______
increased
40
Do we continue with the TCA cycle when we have high levels of ATP?
No. TCA and ETC are inhibited
41
Anapleurtic
Anapleuritic reactions are those that allow intermediates to enter the TCA cycle
42
does the TCA cycle allow anapleuritic reactions?
YES! Intermediates can enter the TCA cycle at various points
43
When we are in a low NRG state, what activates the PDC complex?
high Ca2+ will activate the PDC complex when we are low in NRG
44
Entry sites for AA
``` There are 4 entry sites for AA: OAA, Alpha ketoglurate Succinyl CoA Fumurate ```
45
What enters alpha keto glutarate
1. Gln 2. Arg 3. Pro 4 His will be converted to glutamate and enter alphaketo
46
What enters succinyl CoA?
Threonine Isoleucine Methionine Valine converted to propionyl CoA
47
What enters at fumarate?
Phe Asp Tyr
48
What enters at OAA
Asp | Asn
49
TCA cycle can also provide intermediates for pathways
1. FA synthesis---> citrate | 2. gluconeogensis--> malate
50
Succinyl coA can be used to maek ______, which we useto make ______
Succinyl coA can be used to make PORPHYRIN, which we use to make HEME
51
Disorders of the TCA cycle are common?
No. they're rare and your brain is the first to be affected
52
2 disorders of the TCA cycle
2 oxoglutaric aciduria | Fumurase deficiency
53
How can we test for both?
urinalaysis
54
in 2 oxiglutataric acid and fumarase deficency, what is the first neuro system to be affected
neural
55
2 oxoglutaric aciduria | Fumurase deficiency are autosomal
recessive
56
2 oxoglutaric acis sx
1. metabolic acidosis because we are excreting 2 oxoglutaric acid 2. encephalopathy 3. mental retardation
57
how can we check for 2 oxoglutaric aciduria
we can look at a UA for metabolic acidosis and in crease in 2 oxoglutarate
58
Presentation of fumarse deficiency
1. death before <10 | 2. encephalopathy with speech delays without metabolic acidosis
59
detect for fumarase deficiency
Increased excretion of fumurase, followed by excretion of succinate and lactate and followed by 2 oxoglutarate
60
Is excretion found all of the time in patients with fumurase?
almost, but it is not always fumurase
61
Is there any tx for these dx?
no
62
How are these two dx similar
can cause 1. hypotonia 2. spasticity 3. developmental delays both can cause acute metabolic acidosis and lead to hypoglycemia most are leth <10
63
fumarase deficiency; we can see excretion of
fumurate, succinate, alpha keto glurate and citrate
64
SCS
Succicyl CoA Synthestase deficiency is thought to be caused by mutations in the SUCLA2 and SUCLG1 subunits. As a result, we are going to have problems metabolizing succinate and we will have low mT content
65
As a result of SCS, we will have
problems metabolizing succinate and low mT dna content
66
Sx of SCS
1. Methylmalonyl aciduria 2. hypotonia 3. distonia 4. muscular atrophy 5. sensory and neural impairment
67
Where does oxphos take place?
intermembrane space of the MT
68
What occurs in the MT matrix?
1. TCA cycle | 2. FA oxidation
69
The pH is higher/lower in the mT matrix
HIGHER
70
Can things enter the mT?
YES! the mT has porins that are located on the outside membrane , aloowing things to enter.
71
There are 2 types of redox reactions
1. electron only transfer | 2. reducing equivalent transfer
72
Electron only transfer
electrons are transferred between 2 metal ions
73
_____ are always on the side the the electrons
oxidants
74
Reducing equivlanet transfer
there is a transfer of a H and a electrons
75
What is E0
the standard redox potential
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Reducing agent is being ______
oxidized
77
Oxidizing agent is being ______
reduced
78
Smaller E0
means that the substance has LESS affinity for the electrons and wants to give them up
79
Higher E0
substance has MORE affinity for the electrons and wants them
80
Which will have the smaller E0: reducing agent or oxidiizing agent?
Reducing agent
81
Which will have the higher E0: reducing or oxidizing agent?
Oxiding agent because its getting reduced (RIG)
82
how will electrons transfer in a redox pair?
from low E0 to high E0
83
Difference in E0
delta G
84
How are E0 and standard free NRG related
inversely realted
85
OxPhos occurs where?
inner mT membrane
86
A successful oxphos must
1. transfer the electrons from NADH and FADH2 to O2 2. Create proton gradient 3. which will make ATP
87
Electrons are transferred through a _________ and use the NRG to do what?
Electrons are transferred through a RESPIRATORY chain and use the NRG to pump H+ from the mT matrix, into the inner membrane space
88
what is the proton motive force
the force that promotes H+ ions to be pumped across the membrane
89
What creates the PMF
1. pH gradient | 2. membrane potential
90
pH gradient
As H+ are being pumped across the membrane, the inner membrane space will become more acidic
91
membrane potential
as protons are being pumped from mT membrane--> inner membrane space, the inside will become more -
92
The creation of ATP is made by
ATP synthase (complex v)
93
How many H+ are required
3+1 3 H+ must pass through the channel and 1 must be used for the translocation of ADP
94
What disrupts proton transport through ATPase synthase
Oligomycin
95
OxPhos is mediated by what?
Respiratory chain
96
What is the respiratory chain?
The respiratory chain is a complex of proteins that allows the transfer of electrons: Complex I-V Cytochrome C CoQ (ubiquinone)
97
Mobile carriers in respiratory chain
Cytochrome C and CoQ (ubiqionone)
98
What is CoQ
a lipophillic molecule that is a mobile carrier.
99
___ receives NADH
C1
100
___ receives FADH2
C2
101
What complex converts 1/2 oxygen to water?
CIV
102
How are electrons transferred
NADH enters are complex 1 FADH2 enters at complex 2 both go to CoQ--> C3--> cyctochrome C--> C4, where the electrons go to O to convert to water.
103
What tells us the intactness of the mT
cytochrome C/
104
is CoQ a prosthetic group for C3?
no. its a lipophillic molecule.
105
Which complexes are pumping protons into the inner membrane space?
I, III and IV
106
Oxphos is sensentive to
O2 and | [ATP/ADP] ratios
107
Summary of ETC
NADH and FADH2 donate their electrons to the ETC. Electrons are being transported, creating NRG. This NRG is used to pump protons (I, III and IV) into the inner membrane space. AS a result, a proton gradient and ion gradient are being created. These two gradients create NRG and are used to power ATP synthase, allowing the creating of ATP. H+ is pumped back into the mT membrane
108
Uncoupling says that
electron transfer is COUPLED to proton gradient
109
If the proton gradient is disrupted, what happens to ADP?
ADP uncouples from P and cannot be phosphorylated
110
Result of uncoupling
heat will be created (no ATP synthesis) by permitting proton influx (via UCPs) WITHOUT creating ATP. Thus, they disrupt the proton gradient and do not allow ADP to couple with Pi.
111
In uncoupling, what happens to the TCA cycle and electron transfer to O2?
They receive signals that there is no ATP and TCA and electron transport CONTINUE! allowing bears to live in the summer :)
112
How can we pump H+ ions into the matrix in uncoupling?
Uncoupling proteins like thermogenin (UCP-1), aspirin and DNT are inserted into the membrane and allow the transfer.
113
What do uncoupling protein do?
They will allow heat to be created by permitting proton influx WITHOUT creating ATP. Thus, they disrupt the proton gradient and do not allow ADP to couple with Pi.
114
Heat generates
brown fat tissue
115
in hibernating animals, they do not eat, so they dont make ATP. How do they maintain body temperature?
a UCP (thermogenin) is expressed. This will allow the ATPase to still spin and generate heat
116
How do high NRG substances like FADH2 and NADH enter the MT?
Shuttle systems. Reduced NADH cannot enter the membrane
117
Oxphos occurs where?
inner mT membrane
118
Malate-aspartate shuttle system transports what?
NADH from the [cytosol into the mT matrix]
119
Glycerolphosphate system transports
transports FADH2 from [cytsol--> inner mT membrane].
120
How does the malate-aspartate system work?
NADH cannot pass the membrane. So, its electrons are given to malate. Malate is shuttle via malate-aspartate shuttle. Malate will then go and transfer electrons to NAD in the matrix to be used in the TCA cycle
121
Glycerolphosphate shuttle mechanism
Pyruvate transfers electrons to glycerol 3 phosphate. Glycerol3phosphate is then transferred into the mT via the glycerolphosphate system. electrons from G3P are then donated to FAD
122
Malate aspartate shuttle operates in the
heart liver kidneys
123
In a well-fed stat, what reaction is responsible for transport of NADH from cytsol--> MT?
malate aspartate shyttle
124
glycerolphosphate shuttle works where?
brain and muccle
125
FADH2 from glycerolphosphate system will join the ETC at ___
CoQ