Cardio - Biochemistry - Pyruvate Dehydrogenase Complex; Citric Acid Cycle; Oxidative Phosphorylation Flashcards

1
Q

What are the major substrate (1) and products (3) of the pyruvate dehydrogenase complex?

A

Pyruvate —> acetyl-CoA, CO2, NADH

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2
Q

How many enzymatic subunits make up the pyruvate dehydrogenase complex?

What are they termed?

A

3;

E1, E2, E3

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3
Q

In what order do substrates encounter the enzymes of the pyruvate dehydrogenase complex?

A

E1, E2, E3

(moving inwards from the outer enzyme rings)

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4
Q

What are the five cofactors of the pyruvate dehydrogenase complex?

A

Thiamine (thiamine pyrophosphate) (B1);

riboflavin (B2);

niacin (B3);

pantothenic acid (B5);

lipoic acid

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5
Q

Which B-vitamins are represented in the cofactors of the pyruvate dehydrogenase complex?

A

B1, B2, B3, and B5

(thiamine pyrophosphate (thiamine), FAD (riboflavin), NAD+(niacin), coenzyme A (pantothenic acid))

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6
Q

What vitamins are associated with FAD and NAD+ formation, respectively?

A

Riboflavin, niacin

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7
Q

True/False.

The overall ΔG for the pyruvate dehydrogenase complex reaction is negative.

A

True.

(The reaction is spontaneous and thermodynamically favorable)

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8
Q

Describe the content of the mitochondrial intermembrane space.

A

Essentially contiguous with the cytosol

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9
Q

True/False.

The outer mitochondrial membrane provides a tight barrier to nearly all contents of the cytosol.

A

False;

porins allow free movement of most low-weight cytosolic components

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10
Q

What gives the outer mitochondrial membrane its permeability?

A

Porins

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11
Q

What structures allow pyruvate to enter the mitochondrial matrix?

Where are they found?

A

H+/pyruvate symporters;

the inner mitochondrial membrane (the outer is porous)

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12
Q

CO2 is produced in which step of the pyruvate dehydrogenase complex reaction?

(which enzyme?)

A

Step 1

(E1)

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13
Q

The first step of the pyruvate dehydrogenase complex involves the E_ enzyme. CO2 is released and the remaining 2-carbon substrate ends up bound to __________ __________.

A

1;

thiamine pyrophosphate

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14
Q

True/False.

The substrate of the pyruvate dehydrogenase complex is covalently bound to the enzymatic subunits during the reaction.

A

True.

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15
Q

How many steps are there in the pyruvate dehydrogenase complex reaction?

A

5

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16
Q

There are 5 steps to the pyruvate dehydrogenase complex reaction.

How many of these reactions are focused on creating acetyl-CoA?

What is the purpose of the remaining reactions?

A

The first 3;

to reoxidize lipoyllysine for further reactions

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17
Q

What is the term for the enzymatic process used by the pyruvate dehydrogenase complex in which the substrate is (covalently) bound and passed from one enzyme to the next?

A

Substrate channeling

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18
Q

What high-energy electron carrier is produced in step 4 of the PDH complex?

To what other high-energy electron carrier does it transfer its electrons in step 5?

A

FADH2;

NADH

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19
Q

Thiamine pyrophosphate is involved in which two steps of the PDH complex?

A

The first two

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20
Q

Acetyl-CoA is generated in which step of the PDH complex?

What cofactor is involved?

A

Step 3;

pantothenic acid (vitamin B5)

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21
Q

Match each of the following cofactors to the enzyme of the PDH complex with which they are associated:

Thiamine pyrophosphate (vitamin B1)

Riboflavin (FAD) (vitamin B2)

Niacin (NAD+) (vitamin B3)

Pantothenic acid (part of CoA) (vitamin B5)

Lipoic acid

A

Thiamine pyrophosphate E1

Riboflavin (FAD) E3

Niacin (NAD+) E3

Pantothenic acid (part of CoA) E2

Lipoic acid E2

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22
Q

Which cofactors of the PDH complex are associated with E1?

And E2?

And E3?

A

E1

Thiamine pyrophosphate

E2

Pantothenic acid (part of CoA)

Lipoic acid

E3

Riboflavin (FAD)

Niacin (NAD+)

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23
Q

Put the following cofactors in order of the enzymatic steps in which they participate in the 5 steps of the PDH complex:

Thiamine pyrophosphate

FAD

NAD+

CoA

Lipoic acid

A

Step 1 - Thiamine pyrophosphate

Step 2 - Thiamine pyrophosphate; lipoic acid

Step 3 - Lipoic acid; CoA

Step 4 - FAD

Step 5 - FAD; NAD+

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24
Q

Which enzymatic steps of the PDH complex (5) take place at E1?

At E2?

At E3?

A

1, 2

3

4, 5

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25
Q

The lipoic acid in the PDH complex is bound to what amino acid on E2? What does this form?

A

Lysine;

lipoyllysine

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26
Q

What type of enzyme is stimulated by allosteric regulators such as acetyl-CoA and NADH to inactivate the PDH complex?

How does it accomplish this?

What sort of regulators inhibit this enzymatic activity?

A

PDH kinase;

phosphorylation;

Ca2+, ADP, pyruvate

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27
Q

Phosphorylation and dephosphorylation have what effects on the PDH complex, respectively?

A

Inactivation, activation

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28
Q

What is the main substance that allosterically regulates the phosphatase that activates the PDH complex?

Is it an activator or inhibitor or both?

A

Ca2+;

activator

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29
Q

What role does Ca2+ play in regulating the PDH complex?

A

It allosterically activates the phosphatase that activates the PDH complex

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30
Q

Besides PDH kinase, what two substances directly inhibit PDH complex activity?

Besides PDH phosphatase, what substances directly activate PDH complex activity?

A

Acetyl-CoA, NADH;

AMP, CoA, NAD+

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31
Q

What vitamin is the base of FAD?

What vitamin is the base of NAD+?

What vitamin is the base of CoA?

What vitamin is the base of thiamine pyrophosphate?

A

Riboflavin (B2)

Niacin (B3)

Pantothenic acid (B5)

Thiamine (B1)

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32
Q

A deficiency in thiamine can results in disruption of what two enzyme complexes?

A

The pyruvate dehydrogenase complex;

the α-ketoglutarate dehydrogenase complex

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33
Q

Beriberi disease is due to a deficiency in ________ in the diet.

A

Thiamine

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34
Q

In high-income countries, thiamine deficiencies are most often seen in whom?

A

Alcoholics

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35
Q

What effects can arsenic and mercury have on the pyruvate dehydrogenase complex?

A

They bind the E2 cofactor lipoyllysine

(both substances tightly bind SH groups)

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36
Q

What are the two broad categories of symptoms seen due to disruption of the pyruvate dehydrogenase complex (e.g. Beriberi, mercury poisoning, arsenic poisoning)?

A

Cardiac and neurological symptoms

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37
Q

Leigh’s disease, a subacute necrotizing encephalopathy, is caused by genetic deletions often affecting what enzyme(s)?

A

The E1 subunit

(the PDH complex)

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38
Q

What disease is characterized by acute CNS degeneration as a result of mutations in the E1 subunit of the PDH complex?

A

Leigh’s disease

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39
Q

Most breakdown of substrates (e.g. glycolysis, fatty acid β-oxidation, amino acid breakdown) results in what compound that easily enters the citric acid cycle?

A

Acetyl-CoA

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40
Q

How many high energy compounds are created in one turn of the citric acid cycle?

A

3 NADH

1 FADH2

1 GTP

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41
Q

Which reactions in the citric acid cycle produce either NADH or FADH2?

Which reaction produces GTP through substrate-level phosphorylation?

A

3, 4, 6, and 8;

5

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42
Q

What is the name of the E1 subunit of the PDH complex?

What is the name of the E2 subunit of the PDH complex?

What is the name of the E3 subunit of the PDH complex?

A

Pyruvate dehydrogenase;

dihydrolipoyl transacetylase;

dihydrolipoyl dehydrogenase

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43
Q

What proportion of our ATP is produced by high energy products of the citric acid cycle?

A

2 / 3

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44
Q

Which reactions of the citric acid cycle are redox reactions producing either NADH or FADH2?

A

3, 4, 6, 8

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45
Q

Which reactions of the Kreb’s cycle produce NADH?

Which reaction of the Kreb’s cycle produces FADH2?

Which reaction of the Kreb’s cycle produces GTP?

Which reactions of the Kreb’s cycle produce CO2?

A

NADH - 3, 4, 8

FADH2 - 6

GTP - 5

CO2 - 3, 4

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46
Q

How many reactions go into the tricarboxylic acid cycle?

A

8

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47
Q

Describe the first reaction of the citric acid cycle.

What provides negative feedback to this reaction?

A

Oxaloacetate and acetyl-CoA are combined by citrate synthase;

citrate

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48
Q

Describe the second reaction of the citric acid cycle.

A

Citrate is converted to isocitrate by aconitase

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49
Q

What is the rate-limiting enzyme of the citric acid cycle?

A

Isocitrate dehydrogenase

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50
Q

Describe the third step of the citric acid cycle.

A

Rate-limiting step

Isocitrate is converted to α-ketoglutarate by isocitrate dehydrogenase;

both NADH and CO2 are also produced

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51
Q

Describe the fourth step of the citric acid cycle.

A

α-ketoglutarate is converted to succinyl-CoA by the α-ketoglutarate dehydrogenase complex;

both NADH and CO2 are also produced

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52
Q

What enzyme of the CAC is virtually identical (in function, in vitamin requirements, etc.) to the PDH complex?

A

The α-ketoglutarate dehydrogenase complex

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53
Q

Describe the fifth step of the citric acid cycle.

A

Succinyl-CoA is converted to succinate by succinyl-CoA synthetase;

GTP is also formed

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54
Q

Describe the sixth step of the citric acid cycle.

A

Succinate is converted to fumarate by succinate dehydrogenase;

FADH2 is also formed

(Note: the two F products happen in step 6 — F is also the sixth letter)

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55
Q

Describe the seventh and eighth reactions of the citric acid cycle.

A

7. Fumarate is converted to malate by fumarase;

7. Malate is converted to oxaloacetate by malate dehydrogenase –> NADH is also produced

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56
Q

Name each substrate of the reactions of the citric acid cycle (from acetyl-CoA to oxaloacetate).

A

Acetyl-CoA (+ oxaloacetate) –>

citrate –>

isocitrate –>

α-ketoglutarate –>

succinyl-CoA –>

succinate –>

fumarate –>

malate –>

oxaloacetate

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57
Q

Name each enzyme of the citric acid cycle.

A

Citrate synthase,

aconitase,

isocitrate dehydrogenase,

α-ketoglutarate dehydrogenase complex,

succinyl-CoA synthetase,

succinate dehydrogenase,

fumarase,

malate dehydrogenase

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58
Q

Stoichiometry of the citric acid cycle:

what goes into the cycle?

A

Acetyl-CoA + 3 NAD+ + FAD + GDP + Pi + 2 H2O

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59
Q

Stoichiometry of the citric acid cycle:

what comes out of the cycle?

A

2 CO2 + 3 NADH + FADH2 + GTP + 2 H+ + CoA-SH

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60
Q

How many ATP can be produced from one NADH via oxidative phosphorylation?

How many ATP can be produced from one FADH2 via oxidative phosphorylation?

A
  1. 5;
  2. 5
61
Q

What is the total ATP and GTP production from one acetyl-CoA in one revolution of the citric acid cycle?

A

10 ATP

(3 NADH –> 7.5 ATP

1 FADH2 –> 1.5 ATP

1 GTP)

(really it’s 9 ATP + 1 GTP)

62
Q

ADP and Ca2+ stimulate which steps of the citric acid cycle?

A

3, 4

63
Q

There is a fixed amount of NAD+ in the cell. What does this mean for reactions that require it?

A

If NADH builds up, these reactions will stop

64
Q

What is the most important inhibitory molecule of the citric acid cycle?

Which steps does it inhibt?

A

NADH;

3, 4, 8

65
Q

What is the main inhibitory molecule for citrate synthase?

What is the main inhibitory molecule for steps 3, 4, and 8 of the citric acid cycle?

What are the two main stimulatory substances for steps 3 and 4 of the citric acid cycle?

A

Citrate;

NADH;

Ca2+ and ADP

66
Q

The intermediates of the citric acid cycle can contribute to the synthesis of many other biological compounds.

Citrate can be used in the synthesis of what molecules?

A

Fatty acids, sterols

67
Q

The intermediates of the citric acid cycle can contribute to the synthesis of many other biological compounds.

α-ketoglutarate can be used in the synthesis of what molecules?

A

Glutamate –> other amino acids –> purines

68
Q

The intermediates of the citric acid cycle can contribute to the synthesis of many other biological compounds.

Succinyl-CoA can be used in the synthesis of what molecules?

A

Porphyrins, heme

(also, clorophyll in plants)

69
Q

The intermediates of the citric acid cycle can contribute to the synthesis of many other biological compounds.

Oxaloacetate can be used in the synthesis of what molecules?

A

Aspartate, other amino acids, purines, pyrimidines

70
Q

The intermediates of the citric acid cycle can contribute to the synthesis of many other biological compounds.

What intermediate can be used in the synthesis of fatty acids and sterols?

A

Citrate

71
Q

The intermediates of the citric acid cycle can contribute to the synthesis of many other biological compounds.

What intermediate can be used in the synthesis of glutamate (which can then be used to make other amino acids and/or purines)?

A

α-ketoglutarate

72
Q

The intermediates of the citric acid cycle can contribute to the synthesis of many other biological compounds.

What intermediate can be used in the synthesis of porphyrins or heme (or clorophyll in plants)?

A

Succinyl-CoA

73
Q

The intermediates of the citric acid cycle can contribute to the synthesis of many other biological compounds.

What intermediate can be used in the synthesis of aspartate, other amino acids, and purines and pyrimidines?

A

Oxaloacetate

74
Q

What is the name of the category of reactions that replenish intermediates of the citric acid cycle?

A

Anaplerotic reactions

75
Q

What is the most important anaplerotic (intermediate replenishing) reaction of the citric acid cycle?

A

Pyruvate carboxylase transforming pyruvate into oxaloacetate

76
Q

Besides pyrvuate carboxylase replenishing oxaloacetate from pyruvate, what are some other examples of citric acid cycle intermediates that are replenished via other molecules?

(I.e., what are some other anaplerotic reactions of the CAC?)

A

α-ketoglutarate (from glutamate)

Succinyl-CoA (from valine, isoleucine, or some fatty acids)

Fumarate (from certain amino acids)

Aspartate (from oxaloacetate)

77
Q

How do cytosolic NADH cross the inner mitochondrial membrane to reach the mitochondrial matrix?

A

They don’t

(cytosolic NADH remain in the cytosol; mitochondrial NADH remain in the mitochondrial matrix)

78
Q

True/False.

NADH produced in the cytosol (e.g. via glycolysis) don’t actually cross the inner mitochondrial membrane. Shuttles simply transfer the reducing electrons from the NADH into the mitochondrial matrix to mitochondrial NAD+ or FAD.

A

True.

79
Q

True/False.

NAD+/NADH in the cytosol remain in the cytosol.

(AND)

NAD+/NADH in the mitochondrial matrix remain in the mitochondrial matrix.

A

True.

80
Q

What two shuttles are used to transfer reducing electrons from cytosolic NADH to mitochondrial NAD+ or FAD?

A

The glycerol phosphate shuttle;

the malate-aspartate shuttle

81
Q

In what tissues is the glycerol phosphate shuttle found?

In what tissues is the malate-aspartate shuttle found?

A

Most tissues;

primarily the liver and heart

82
Q

How much of cellular energy is produced by the TCA and oxidative phosphorylation?

A

90 - 95%

83
Q

The TCA has catabolic and anabolic components. The term describing this situation is:

A

Amphibolic

84
Q

What molecule is basically the goal product of glycolysis, beta-oxidation, etc. that feeds into the TCA?

A

Acetyl-CoA

85
Q

In most tissues, what percentage of PDH complexes are active?

In what tissue is this not true and most PDH complexes are always activated?

A

< 50%;

neural/brain tissues

86
Q

Can glucose cross the blood-brain barrier?

Can fatty acids cross the blood-brain barrier?

Can amino acids cross the blood-brain barrier?

Can ketones cross the blood-brain barrier?

A

Yes;

no;

yes;

yes

87
Q

What is the result of Leigh’s syndrome (a genetic defect in the E1 subunit of the PDH complex)?

A

Lack of sufficient glucose metabolism –> infantile neuronal degeneration

88
Q

Ketogenic amino acids can be transformed directly into what high-energy molecule?

A

Acetyl-CoA

(or ketones)

89
Q

Of the two shuttles used to transport high-energy electrons into the mitochondrial matrix, which involves the transfer of an actual molecule?

A

The malate-aspartate shuttle transfers malate across

(the glycerol phosphate shuttle just sends the electrons over from NADH to FAD)

90
Q

How many ATP are made from one glucose molecule using the malate-aspartate shuttle?

How many ATP are made from one glucose molecule using the glycerol phosphate shuttle?

A

32;

30

91
Q

How many ATP are made from a single NADH molecule using the malate-aspartate shuttle?

How many ATP are made from a single NADH molecule using the glycerol phosphate shuttle?

A
  1. 5;
  2. 5
92
Q
  1. 5 ATP are made from a single NADH molecule using the malate-aspartate shuttle.
  2. 5 ATP are made from a single NADH molecule using the glycerol phosphate shuttle.

What explains this descrepency?

A

Malate-aspartate gives its electrons to NADH

Glycerol phosphate gives its electrons to FADH2

  • (also, the reason it is not 3 and 2, respectively, is that there is a dissipation of the proton gradient due to:*
  • molecules (e.g. pyruvate, glutamic acid, malate) being transported across the inner mitochondrial membrane))*
93
Q

What enzyme and what cofactor are necessary for the transamination reactions of the malate-aspartate shuttle?

A

Aspartate transaminase (also, aminotransferase) (AST);

pyridoxal phosphate (B6 derivative)

94
Q

What cofactor is necessary for transamination reactions (e.g. those of the malate-aspartate shuttle)?

A

Pyridoxal phosphate (B6 derivative)

95
Q

Describe the first reaction of the malate-aspartate shuttle.

A

Oxaloacetate + NADH → Malate + NAD+

96
Q

Describe the malate-aspartate shuttle in terms of what enters the mitochondrial matrix and what leaves.

A
97
Q

In the transamination step of the malate-aspartate shuttle, AST converts aspartate into ___________.

α-ketoglutarate is converted to ___________.

A

Oxaloacetate (which will then become malate;

glutamate

98
Q

Describe the basic mechanism of the glycerol phosphate shuttle.

A
99
Q

What enzyme of the malate-aspartate shuttle can be used as a serum marker of liver health?

A

Aspartate transaminase (AST)

(also known as aspartate aminotransferase)

100
Q

Pyridoxal phosphate (B6 derivative) is an important cofactor in what type of reaction (e.g. that found in the malate-aspartate shuttle)?

A

Transaminations

101
Q

If long chain fatty acids are in the mitochondria, what does this indicate about the cell? Is it in the well-fed or fasting state?

A

Fasting

102
Q

Do long chain fatty acids have any effect on the PDH complex in the mitochondria?

A

Yes;

they are inhibitory (they indicate that the cell is in the fasting state)

103
Q

The glycerol phosphate shuttle starts with ______ on the outside of the inner mitochondrial membrane passing electrons to ______ in the mitochondrial matrix.

How many ATP result from one cytosolic NADH via this process?

A

NADH,

FAD;

1.5 (via mitochondrial FADH2)

104
Q

The malate-aspartate shuttle starts with ______ on the outside of the inner mitochondrial membrane passing electrons to ______ in the mitochondrial matrix.

How many ATP result from this process?

A

NADH,

NAD+;

2.5 (transported via malate)

105
Q

What happens to the unused free energy made by the oxidation of NADH during oxidative phosphorylation?

A

As much as 65% is released as heat and contributes to thermoregulation

106
Q

Describe the permeability of the outer and inner mitochondrial membranes.

A

Outer: permeable to most ions and metabolites

Inner: impermeable to nearly all ions and small molecules

107
Q

What is the final electron acceptor in the electron transport chain (ETC)?

What is the final product of the ETC?

A

O2;

H2O

108
Q

Describe the difference in pH across the inner mitochondrial membrane.

A

Intermembrane space: lower pH (higher [H+] due to ETC)

Mitochondrial matrix: higher pH

109
Q

In which direction are H+ ions pumped in regards to mitochondrial structure?

A

From the matrix to the intermembrane space (across the inner mitochondrial membrane)

110
Q

What powers the ATP synthase complex?

A

Dissipating proton motive force —> H+ flowing down their concentration gradient

111
Q

In order, name each component of the chain of electron transfer in the ETC.

A

NADH –> Complex I –> Complex II –> Coenzyme Q –> Complex III –> Cytochrome C –> Complex 4 –> O2

112
Q

Of the electron carriers present in the electron transport chain, which carrier moves freely in the membrane without an attached protein?

A

Coenzyme Q

113
Q

How many different forms of cytochromes exist?

A

3 —> types A, B, and C

114
Q

Cytochromes are very similar to what part of hemoglobin?

A

The protoporphyrin ring

115
Q

In what state must the iron (Fe) atoms in protoporphyrin rings (e.g. hemoglobin, the cytochromes) be to able to carry electrons?

A

The reduced state (ferrous) (Fe2+)

116
Q

In the second type of electron carriers, iron-sulfur proteins, what side chains coordinate the central iron (Fe) molecule?

A

Cysteine sulfur-containing side groups

117
Q

Coenzyme Q is unique in that it has 3 redox states. Why is this important?

A

Coenzyme Q can carry 2 electrons

118
Q

After the first reaction involving coenzyme Q, ubiquinone (Q), is reduced to what molecule? What state is this?

What molecule is semiquinone (QH) reduced to? What redox state is this for coenzyme Q?

A

Semiquinone (QH) –> this is its first redox state

Ubiquinol (QH2) –> this is its second redox state

119
Q

Through which of its two subunits does ATP synthase allow H+ ions to flow down their concentration gradient?

A

The Fo subunit

120
Q

What would happen if a drug inhibited the function of the F1 subunit of ATP synthase?

A

No ATP synthesis

121
Q

How does the F0 subunit facilitate ADP binding to the F1 subunit?

At which subunit of the F1 do ADP and Pi bind?

A

As the C10 ring spins, a conformational change occurs;

the β subunit

122
Q

Describe how each of the following substances inhibits electron flow in the ETC:

Rotenone

Antimycin A

Cyanide or CO

A

Rotenone - Complex I –> Coenzyme Q

Antimycin A - Cytochrome B –> Cytochrome C1

Cyanide or CO - Cytochrome A –> O2

123
Q

If the ETC is halted in such a state that NADH dehydrogenase (complex I) is reduced and the rest of the electron transport chain is oxidized, which of the following is likely responsible?

Carbon monoxide

Rotenone

Antimycin A

Cyanide

A

Rotenone poisoning - Inhibition of NADH dehydrogenase (complex 1) passing electrons to Coenzyme Q

124
Q

Antimycin A is a bacterial product that can inhibit energy production.

What are the effects of its inhibition on the ETC?

A

Block complex III from becoming reduced by coenzyme Q

125
Q

If cytochrome C oxidoreductase is unable to be reduced, what type of poisoning has occurred, and what molecule is now unable to reoxidize?

A

Antimycin A –>

Ubiquinol (2nd redox state of coenzyme Q) stays in its reduced form.

126
Q

Cyanide and carbon monoxide are particularly dangerous toxins.

Describe their mechanism of action on energy production.

A

These inhibit cytochrome oxidase (complex IV)

127
Q

After releasing electrons from the cytochrome complex, to what state do iron molecules return?

A

The oxidized state (Fe3+)

128
Q

There are four principal ways for electrons to be fed into coenzyme Q, discuss these contributors.

A
  • From NADH (via Complex 1)
  • From FADH2 (via Complex 2)
  • From FADH2 (via glycerol-3-phosphate shuttle)
  • From fatty acid oxidation
129
Q

How many H+ ions must pass through the C10 ring and spin the F1 subunit in order to provide enough energy to oxidatively phosphorylate ADP and Pi?

A

~4 H+ per ATP molecule

130
Q

NADH enters the ETC at which complex?

How many H+ will be pumped across the inner mitochondrial membrane?

A

NADH dehydrogenase (complex I);

10

131
Q

FADH2 enters the ETC at which complex?

How many H+ will be pumped across the inner mitochondrial membrane?

A

Succinate dehydrogenase (complex II);

6

132
Q

Molecular oxygen is combined with protons to form water at what protein complex of the ETC?

A

Complex IV (cytochrome oxidase)

133
Q

The F0 portion of ATP synthase is the:

The F1 portion of ATP synthase is the:

A

Rotor / shaft (proton movement);

head (ATP production)

134
Q

What is the alternative name for complex IV of the ETC?

A

Cytochrome oxidase

135
Q

Discuss the effects of a chemical uncoupler on the ETC.

A

Proton force dissipated = reduced ATP synthase activity

Presents alternative source of proton motive force dissipation -

–> instead of flowing down ATP synthase, they reenter the matrix a different way

136
Q

Dinitrophenol (DNP) is a chemical uncoupler that can decrease energy production. Describe its uncoupling mechanism

A

It is a hydrophobic molecule and carries protons through the inner mitochondrial membrane

137
Q

A chemical uncoupler will have what effect on bodily temperature regulation?

Describe a natural uncoupler found in young infants.

A

May cause hyperthermia as H+ gradient dissipation energy is not used to phosphorylate ADP and Pi.

Thermogenin is found in brown fat (newborns). It helps them to regulate body temperature in the beginning years of life

(non-shivering heat)

138
Q

Describe the mechanisms of several uncoupling agents that inhibit ATP synthase activity.

A

Thermogenin (in brown fat) –> forms pores in inner mitochondrial membrane

DNP, FCCP –> hydrophobic proton carriers

Valinomycin –> K+ ionophore

139
Q

In a low energy state, discuss the state of oxidative phosphorylation.

A

Greater availability of ADP in low energy state –> increase in oxidative phosphorylation

140
Q

Discuss the regulation of the electron transport chain under acidic conditions.

Discuss the regulation of the electron transport chain under hypoxic conditions.

A

Dimerizations / inhibition of the F1 subunit;

lack of O2 final electron acceptor –> decrease in OP, increase in anaerobic glycolysis

141
Q

Under increased glycolysis, there is a buildup of pyruvic acid and lactic acid in the cytosol. Discuss the effect this would have on ATP synthase and overall energy production.

A

Lower pH in the cytosol (more acidic) causes F1 dimerization and inhibition of ATP synthase activity

142
Q

Pyruvate/H+ symporters have what immediate effect on ATP synthase activity?

A

Decreased energy production per pyruvate due to slight dissipation of the proton gradient

143
Q

For both major shuttles, indicate the total ATP yield in the oxidative phosphorylation pathway.

A

Glycerol phosphate shuttle - 30 ATP

Malate-aspartate shuttle - 32 ATP

144
Q

What are the three main types of electron transporter within the electron transport system that are constantly being reduced and oxidized?

A
  1. Cytochromes (A,B,C)
  2. Iron-sulfer side chains (Cysteine)
  3. Coenzyme Q
145
Q

What are the names of the four complexes of the ETC?

A

NADH dehydrogenase (I)

Succinate dehydrogenase (II)

Ubiquinone cytochrome C oxidoreductase (III)

Cytochrome oxidase (IV)

146
Q

How does oligomycin affect the ETC?

A

It binds the F0 rotor of ATP synthase

(inhibiting proton movement)

147
Q

True/False.

Cellular respiration is dependent on ATP synthase function.

A

True.

This is called respiratory control.

148
Q

All the complexes of the ETC are in the _________ form until receiving electrons from NADH or FADH2.

A

Oxidized

149
Q

What molecule allows for transport of ATP out of the mitochondrial matrix?

For what does it exchange it?

What drug blocks this antiporter?

A

The ATP-ADP translocase;

ADP;

atractyloside