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Flashcards in Mitochondria Bioenergetics Deck (125):
1

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

We need to remake NAD+.

2

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

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

3

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

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

4

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

The TCA cycle

5

What are we doing in the TCA cycle?

oxidizing carbon so that we can harness the NRG.

6

Is the TCA cycle anabolic, catabolic or amphibolic?

Amphibolic

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

7

Where does the TCA cycle occur?

Mitochondrial matrix

8

3 stages of TCA cycle

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

9

Products of the TCA cycle are

3 NADHs,
1 FADH2
1 GTP

And 2 CO2s are released.

10

Why is the TCA cycle important?

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!

11

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

what sources and how

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

12

In acetyl coA, where is the high NRG bond?

thioester bond

13

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

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

14

How do we convert pyruvate to acetyl coA?

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

15

When is the PDC inactive?

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.

16

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

the PDC is always phosphorylated, making it INACTIVE.

17

So the PDC is active when it is

dephosphorylated

18

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

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!

19

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

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

20

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

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

21

Inhibitors of PDC

NADH
ATP
Acetyl CoA

22

Activators of PDC

Pyruvate and
ADP

23

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

We need NRG we so want to upregulate it.

24

aerobic respiration is coupled with ______

OxPhos

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

76

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