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T1 - Integrated (Full Review) > Biochemistry - Cardiology Block (I) > Flashcards

Biochemistry - Cardiology Block (I) 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

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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13
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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14
Q

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

A

5

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15
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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16
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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17
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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18
Q

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

A

The first two

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19
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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20
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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21
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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22
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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23
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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24
Q

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

A

Inactivation, activation

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25
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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26
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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27
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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28
Q

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

A

Thiamine

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29
Q

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

A

Alcoholics

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30
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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31
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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32
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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33
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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34
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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35
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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36
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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37
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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38
Q

How many reactions go into the tricarboxylic acid cycle?

A

8

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39
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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40
Q

Describe the second reaction of the citric acid cycle.

A

Citrate is converted to isocitrate by aconitase

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41
Q

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

A

Isocitrate dehydrogenase

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42
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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43
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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44
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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45
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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46
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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47
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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48
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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49
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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50
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
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51
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)

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52
Q

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

A

3, 4

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53
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

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54
Q

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

Which steps does it inhibt?

A

NADH;

3, 4, 8

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55
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

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56
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

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57
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)

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58
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

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59
Q

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

A

Anaplerotic reactions

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60
Q

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

A

Pyruvate carboxylase transforming pyruvate into oxaloacetate

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61
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)

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62
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)

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63
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.

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64
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.

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65
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

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66
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

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67
Q

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

A

90 - 95%

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68
Q

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

A

Acetyl-CoA

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69
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

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70
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

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71
Q

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

A

Acetyl-CoA

(or ketones)

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72
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)

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73
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

74
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
75
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))*
76
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)

77
Q

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

A

Pyridoxal phosphate (B6 derivative)

78
Q

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

A
79
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

80
Q

Describe the basic mechanism of the glycerol phosphate shuttle.

A
81
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)

82
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

83
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

84
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)

85
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)

86
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)

87
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

88
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

89
Q

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

What is the final product of the ETC?

A

O2;

H2O

90
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

91
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)

92
Q

What powers the ATP synthase complex?

A

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

93
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

94
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

95
Q

How many different forms of cytochromes exist?

A

3 —> types A, B, and C

96
Q

Cytochromes are very similar to what part of hemoglobin?

A

The protoporphyrin ring

97
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+)

98
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

99
Q

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

A

Coenzyme Q can carry 2 electrons

100
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

101
Q

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

A

The Fo subunit

102
Q

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

A

No ATP synthesis

103
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

104
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

105
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

106
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

107
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.

108
Q

Cyanide and carbon monoxide are particularly dangerous toxins.

Describe their mechanism of action on energy production.

A

These inhibit cytochrome oxidase (complex IV)

109
Q

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

A

The oxidized state (Fe3+)

110
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

111
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

112
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

113
Q

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

A

Complex IV (cytochrome oxidase)

114
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)

115
Q

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

A

Cytochrome oxidase

116
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

117
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

118
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)

119
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

120
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

121
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

122
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

123
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

124
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

125
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
126
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)

127
Q

How does oligomycin affect the ETC?

A

It binds the F0 rotor of ATP synthase

(inhibiting proton movement)

128
Q

True/False.

Cellular respiration is dependent on ATP synthase function.

A

True.

This is called respiratory control.

129
Q

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

A

Oxidized

130
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

131
Q

True/False.

Glucose molecules that just entered the liver are likely to both be phosphorylated to glucose 6-phosphate and enter both glycolysis and the pentose phosphate shunt.

A

True.

132
Q

Where does the pentose phosphate pathway take place?

What types of tissue needs are answered by increased pentose phosphate pathway activity?

A

In the cytosol;

NADPH needs (e.g. for fatty acid synthesis, cholesterol/steroid synthesis, glutathione reduction)

133
Q

What substance is very important as a reducing agent in fatty acid/steroid/cholesterol synthesis?

Via what pathway is it produced?

A

NADPH;

the pentose phosphate pathway

134
Q

What are the two phases of the pentose phosphate pathway?

A

Oxidative phase (irreversible)

Nonoxidative phase (reversible)

135
Q

Describe the general reaction that occurs in the oxidative phase of the pentose phosphate pathway.

A

Glucose-6-phosphate is oxidized to:

  • 2 NADPH
  • Ribulose-5-phosphate
  • CO2

(irreversible)

136
Q

Describe the general reaction that occurs in the nonoxidative phase of the pentose phosphate pathway.

A

Ribose-5-phosphate is converted to:

  • Nucleic acids
  • GAP (glyceraldehyde 3-phosphate)
  • F6P

(reversible)

137
Q

What is the first enzyme of the oxidative phase of the pentose phosphate pathway?

This enzyme is especially important because it is the:

A

Glucose-6-phosphate dehydrogenase;

rate-determining enzyme

141
Q

What pathway uses ribose-5-phosphate as a substrate?

A

Nucleotide biosynthesis (DNA synthesis)

142
Q

The pentose phosphate pathway committed step is performed by which enzyme?

A

Glucose-6-phosphate dehydrogenase

143
Q

Differentiate between the structure of ribulose-5-phosphate and ribose-5-phosphate sugars in the pentose phosphate pathway.

A

RibULOSE-5-phosphate = keto sugar

RibOSE-5-phosphate = aldose sugar

(Note: image is of trioses, not pentoses)

144
Q

The isomerization of ribulose-5-phosphate to ribose-5-phosphate occurs as part of what reaction in the oxidative phase of the pentose phosphate pathway?

A

The 4th (and final) reaction

(beginning of nonoxidative steps)

145
Q

Transketolase is the enzyme used in the 2nd step of the nonoxidative phase.

What cofactor is required by this enzyme?

A

Thiamine pyrophosphate

(derivative of vitamin B1)

146
Q

NADPH is used as a reducing agent for which biosynthetic pathways?

A

Fatty acid synthesis

Steroid/cholesterol synthesis

Glutathione reduction

147
Q

Describe the ‘shell game’ that the nonoxidative phase of the pentose phosphate shunt uses to move carbons around and get from ribose 5-phosphate to any of the following:

glyceraldehyde 3-phosphate, fructose 6-phosphate, glucose 6-phosphate

A
148
Q

How does the nonoxidative phase of the pentose phosphate shunt get from a pentose (ribose 5-phosphate) back to trioses (glyceraldehyde 3-phosphate) and hexoses (fructose 6-phosphate, glucose 6-phosphate)?

A

2-carbon (taken from X5P) added to 5-carbon (R5P)

–> 7-carbon (S7P)

1-carbon taken from S7P (and added to 3-carbon (G3P) –> 4-carbon (E4P))

–> F6P

–> G6P

149
Q

What three glycolytic intermediates can be made from the pentose phosphate shunt?

From which phase?

A

Glyceraldehyde 3-phosphate, fructose 6-phosphate, glucose 6-phosphate;

nonoxidative

150
Q

The nonoxidative phase of the pentose phosphate pathway requires 3 enzymes for its four reactions

- epimerase, transketolase & transaldolase -

which one(s) require thiamine pyrophosphate as a cofactor?

A

Only transketolase

151
Q

Discuss the role of the epimerase used in the nonoxidative phase of the pentose phosphate pathway.

A

It converts ribulose-5-phosphate to its epimer xylulose-5-phosphate

152
Q

What two glycolytic intermediates are formed by the reactions of xylulose-5-phosphate (from the nonoxidative phase of the pentose phosphate pathway)?

A

Glyceraldehyde-3-phosphate;

fructose-6-phosphate

153
Q

As concentrations of NADPH increase in the cell, how will this regulate enzymatic function?

A

Strongly inhibits glucose-6-phosphate dehydrogenase

(initial enzyme in PPP)

154
Q

What is the main difference between NADPH and NADH in their function/use?

A

NADPH - used for biosynthesis

NADH - used for energy production

155
Q

True/False.

If a cell needs (1) only NADPH, or (2) only ribose 5-phosphate, or (3) both, it can tailor the pentose phosphate shunt to meet its needs.

A

True.

Only NADPH - Ribulose 5-P turned back into G6P (goes back into oxidative phase)

Both - Ribulose 5P turned into ribose 5-P

Only ribose 5-phosphate - Oxidative portion shut down; nonoxidative runs in reverse (F6P and GAP –> R5P)

156
Q

For each individual glucose molecule that enters the pentose phosphate pathway, how many NADPH are produced?

A

2 NADPH per G6P

158
Q

How would a cell that requires a lot of nucleotide synthesis and no NADPH regulate the pentose phosphate pathway?

A

Only the nonoxidative portion matters, but in reverse –> F6P and GAP are converted to R5P

(Oxidative phase will be shut down to prevent ANY NADPH production (which would inhibit glucose-6-phosphate dehydrogenase and prevent ribose-5-phosphate production).)

159
Q

If the oxidative phase of the pentose phosphate pathway is effectively shut down, what would a cell use to create a steady stream of ribose-5-phosphate?

A

Glycolytic intermediates:

glyceraldehyde-3-phosphate and fructose-6-phosphate

161
Q

What is the major controlling factor for the pentose phosphate pathway?

What other factor plays an important role?

A

NADPH concentrations;

xylulose 5-phosphate levels

162
Q

Discuss the effect of rising xylulose-5-phosphate levels in the cell following a large meal.

(Note: Xylulose 5 -phosphate is produced in the pentose phosphate pathway.)

A

Xylulose-5-phosphate activates phosphoprotein phosphatase (PP2A);

fed state –> dephosphorylates PFK-2/FBPase-2 enzyme –> increases glycolysis / decreases gluconeogenesis

163
Q

What is the importance of creating xylulose-5-phosphate from ribulose-5-phosphate?

A

Xylulose-5-phosphate is a regulatory molecule for carbohydrate and lipid metabolism.

*X5P structure is also used to form glycolytic intermediates

164
Q

What is the role of phosphoprotein phosphatase (PP2A)?

A

Dephosphorylates PFK-2/FBPase-2 enzyme

–>

Increases glycolysis / decreases gluconeogenesis

165
Q

When the PFK-2/FBPase-2 enzyme is dephosphorylated, what results?

A

PFK-2 is activated

FBPase-2 is inhibited

(increases glycolysis / decreases gluconeogenesis)

166
Q

When PFK-2 is activated by the regulatory activity of xylulose-5-phosphate, what are the downstream effects?

A

PFK-2 increases fructose-2,6-bisphosphate levels,

activating glycolysis and inhibiting gluconeogenesis

167
Q

When xylulose-5-phosphate levels rise and induce their regulatory actions on phosphoprotein phosphatase and the PFK-2/FBPase-2 enzyme, what is the end result of this regulatory pathway?

A

Increased fructose-2,6-bisphosphate levels –> increased levels of acetyl-CoA (through glycolysis)

169
Q

How does the tripeptide (3 amino acids) glutathione help protect the cell membrane from reactive oxygen species (ROS)?

A

Glutathione is an antioxidant (the SH group is easily oxidizable);

also, it and glutathione peroxidase decrease H2O2 levels

171
Q

How many molecules of glutathione are needed to reduce H2O2 to H2O? What redox state do the glutathione molecule(s) need to be in?

A

2;

reduced state (GSH, not GS-SG)

172
Q

What are the three enzymes of the nonoxidative phase of the pentose phosphate shunt?

A

Epimerase, transketolase, transaldolase

178
Q

What are the steps of the respiratory (oxidative) burst (from O2 to hypochlorite)?

What cells perform this function to create reactive oxygen species?

A

NADPH + 2 O2 – (NADPH oxidase) –> NADP+ + O2-

2 O2- – (superoxide dismutase) –> H2O2

H2O2 – (myeloperoxidase) –> HOCl

monocytes, macrophages, neutrophils

179
Q

What three enzymes are part of the respiratory (oxidative) burst?

What NADPH-dependent enzyme helps limit its damaging effects?

A

NADPH oxidase, superoxide dismutase, myeloperoxidase;

glutathione peroxidase

182
Q

What is the role of NADPH in red blood cells?

A

Reduce glutathione

–>

Protect membrane from oxidative damage (free radicals)

184
Q

Describe how a cell can modify the pentose phosphate shunt for each of the following conditions of need:

(1) only NADPH
(2) only ribose 5-phosphate
(3) both

A

Only NADPH - Ribulose 5-P turned back into G6P (goes back into oxidative phase)

Only ribose 5-phosphate - Oxidative portion shut down; nonoxidative runs in reverse (F6P and GAP –> R5P)

Both - Ribulose 5P turned into ribose 5-P

185
Q

How would a red blood cell regulate the two phases of the pentose phosphate pathway?

Will it produce NADPH, ribose 5-phosphate, or both?

A

RBC has no nucleus (and so no DNA synthesis) — oxidative phase will be uninhibited to produce only NADPH

(the nonoxidative phase will take ribulose-5-phosphate and convert it to glucose-6-phosphate so it can reenter the oxidative phase)

188
Q

How much energy can be made from NADPH in oxidative phosphorylation?

A

None; it is only a biosynthetic reducing agent.

(It is not like NADH.)

196
Q

If high levels of glucose-6-phosphate leads to increased NADPH, and high levels of ribose-5-phosphate (also X5P) lead to increased acetyl-CoA, what metabolic process will ultimately follow?

A

NADPH and Acetyl-CoA both increase fatty acid synthesis

199
Q

Reduced glutathione (90%) is:

Oxidized glutathione (10%) is:

A

Glutathione-SH

Glutathione disulfide (glutathione-S—S-glutathione)

201
Q

What enzyme reduces glutathione (GSSG to 2 GSH)?

What enzyme oxidizes glutathione (2 GSH to GSSG) and decreases intracellular hydrogen peroxide?

A

Glutathione reductase;

glutathione peroxidase

202
Q

How does NADPH help with glutathione peroxidase-mediated protection against H2O2?

A

NADPH provides the reducing power for glutathione reductase

203
Q

What is the role of glutathione reductase?

A

Take an oxidized glutathione dimer (GSSG) and tranforms it into two molecules of reduced glutathione (GSH)

204
Q

What is the most common enzyme disorder?

A

Glucose-6-phosphate dehydrogenase (G6PD) deficiency

205
Q

Quinine (an antimalarial drug) is oxidative and causes an increase in reactive oxygen species (ROS), sometimes leading to a decrease in a patient’s RBC count.

How does quinine do this?

A

Hemolytic anemia (especially in individuals with G6PD deficiency)

  • Decreased NADPH —>*
  • Glutathione can’t be reduced –>*
  • Membrane damaged by ROS*
206
Q

An alcoholic man shows up to the ER in a hemolytic crisis.

What is the most likely underlying cause?

A

Thiamine deficiency

(affects production of NADPH by the pentose phosphate pathway)

209
Q

What NADPH-dependent enzyme decreases the amount of H2O2 in the cell?

A

Glutathione peroxidase

2 GSH –> GSSG

H2O2 –> 2 H2O

210
Q

True/False.

Oxidizing drugs can easily deplete reduced glutathione stores and increase the effects of oxidation damage on RBCs.

A

True.

211
Q

What population is at-risk for favism?

What substances should they avoid? Why?

A

Individuals with glucose 6-phosphate dehydrogenase (G6PD) deficiency;

oxidizing drugs, fava beans;

loss of reduced glutathione –> hemolytic anemia

T1 - Integrated (Full Review) (29 decks)

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