The Pyruvate Dehydrogenase Complex and the TCA cycle. Flashcards

1
Q

What are co-enzymes?

A

Small organic molecules that will help an enzyme perform its job. Co-enzymes are often derived from vitamins.

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2
Q

What are kinases?

A

These enzymes will add phosphate groups to proteins.

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3
Q

What amino acid residues get phosphorylated?

A

Serine.

Threonine.

Tyrosine residues.

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4
Q

What are phosphatases?

A

These enzymes will remove phosphate groups from proteins.

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5
Q

What is the final product of glycolysis?

A

2 Pyruvate molecules.

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6
Q

How many carbons does each pyruvate molecule have?

A

3.

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7
Q

What happens when pyruvate is oxidised further?

A

All of the electrons are removed to form CO2 and water.

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8
Q

Is the breakdown of pyruvate catabolic or anabolic?

A

Catabolic.

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9
Q

What are the goals of the PDH cycle and the ETC?

A

To get energy out of pyruvate.

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10
Q

Where are the 2 molecules of pyruvate formed?

A

In the cytoplasm.

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11
Q

Where are the enzymes for the TCA cycle and the PDH cycle found?

A

In the mitochondria.

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12
Q

What are the main energy producers in the cell?

A

The mitochondria.

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13
Q

Describe the interior of the mitochondria?

A

The interior of a mitochondrion is made up of 2 layers or membranes that are separated by a space.

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14
Q

What are the 2 membranes in the mitochondria called?

A

The outer and inner membrane.

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15
Q

What is the space between the outer an inner membrane called?

A

The inter-membranous space.

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16
Q

Why is the inner mitochondrial membrane invaginated?

A

To increase surface area.

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17
Q

Is the inner mitochondrial membrane easy for molecules to penetrate?

A

No.

It is highly impermeable.

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18
Q

Where in the mitochondria does the TCA cycle and PDH step occur?

A

In the mitochondrial matrix.

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19
Q

Where is the mitochondrial matrix located?

A

On the inside of the inner mitochondrial membrane.

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20
Q

What metabolic functions occur in the outer membrane of the mitochondria?

A

Phospholipid synthesis.

Fatty acid de-saturation.

Fatty acid elongation.

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21
Q

What metabolic functions occur in the inner membrane of the mitochondria?

A

Electron transport.

Oxidative phosphorylation.

Metabolite transport.

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22
Q

What metabolic functions occur in the inter membranous space of the mitochondria?

A

Nucleotide phosphorylation

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23
Q

What metabolic functions occur in the mitochondrial matrix of the mitochondria?

A

TCA cycle.

Pyruvate oxidation.

DNA replication.

Beta oxidation of fats.

Protein synthesis.

RNA synthesis.

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24
Q

Does the PDH step or the TCA cycle occur first?

A

The pyruvate molecules enter the PDH complex first then go into the TCA cycle.

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25
Q

What is formed in the PDH complex?

A

Pyruvate is oxidised to ACoA.

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26
Q

How many carbons does ACoA have?

A

2.

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27
Q

Are the any by products of the oxidation of pyruvate to ACoA in the PDH step?

A

The carbon that is removed from pyruvate is lost as CO2.

The energy from the oxidation forms an NADH.

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28
Q

What molecule enters the TCA cycle?

A

ACoA.

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29
Q

Can the formation of ACoA from pyruvate be reversed?

A

No.

The reaction is irreversible.

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30
Q

Is the PDH complex a single enzyme or multiple enzymes?

A

A single enzyme.

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31
Q

Where is the PDH complex found?

A

In the mitochondrial matrix.

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32
Q

How many enzymes does the PDH complex contain?

A

3.

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33
Q

How many regulatory proteins does the PDH complex contain?

A

2.

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34
Q

How many coenzymes does the PDH complex require so that it can function?

A

5.

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35
Q

What are the 3 enzymes or catalytic proteins in the PDH complex?

A

Pyruvate dehydrogenase.

Dihydrolipoyl dehydrogenase.

Dihydrolipoyl transacetylase.

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36
Q

What are the 2 regulatory proteins in the PDH complex?

A

Protein kinase (PDH kinase).

Protein phosphatase (PDH phosphatase).

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37
Q

What are the 5 coenzymes required by the PDH complex?

A

NAD+.

FAD.

Thiamine pyrophosphate (TPP).

Lipoic acid.

CoASH (co-enzyme A).

Nobody.

Fucks.

The.

Large.

Chicks.

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38
Q

What happens if a coenzyme is missing from the PDH complex?

A

Then the PDH complex cannot function.

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39
Q

Which coenzymes are vitamins?

A

NAD+.

FAD.

Thiamine pyrophosphate (TPP).

CoASH (co-enzyme A).

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40
Q

Which coenzyme is not a vitamin?

A

Lipoic acid.

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41
Q

How are the co-enzymes that are vitamins in the PDH complex acquired?

A

From the diet.

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42
Q

What enzymes in the PDH complex are involved in the conversion of pyruvate to ACoA?

A

All 3 of them.

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43
Q

Which co-enzymes will carry the acetyl group through the complex and to give it to CoA and form ACoA?

A

Co-ASH and TPP.

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44
Q

Which co-enzymes will transfer electrons from substances that have been oxidised to eventually form NADH.

A

Lipoic acid, NAD+ and FAD

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45
Q

What will be the output of 1 pyruvate molecule in the PDH complex?

A

1 ACoA, 1 Pyruvate and 1 CO2.

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46
Q

What will be the output of 1 glucose molecule in the PDH complex?

A

2 ACoA, 2 Pyruvate and 2 CO2.

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47
Q

When will the PDH complex be active?

A

When it is de-phosphorylated.

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48
Q

What will de-phosphorylate the PDH complex?

A

The regulatory enzyme, PDH phosphatase.

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49
Q

What stimulates the de-phosphorylation of the PDH complex by PDH phosphatase?

A

High levels of insulin in the liver.

High levels of calcium or magnesium in skeletal muscle.

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50
Q

When will the PDH complex not be active?

A

When it is phosphorylated.

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51
Q

What will phosphorylate the PDH complex?

A

The regulatory enzyme, PDH kinase.

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52
Q

What will activate PDH kinase?

A

ATP.

ACoA.

NADH.

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53
Q

Other than the PDH complex, what other methods can be used to create ACoA?

A

Triglycerides to ACoA.

Protein to ACoA.

Glycogen to ACoA.

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54
Q

How does glycogen for ACoA?

A

It can be broken down by glycogenolysis to form glucose.

Glucose can then form pyruvate.

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55
Q

What are triglycerides?

A

Fats which are a form of stored energy.

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56
Q

How can triglycerides form ACoA?

A

Triglycerides are broken down to glycerol and free fatty acids by lipolysis.

Free fatty acids are then broken down via beta oxidation to form ACoA.

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57
Q

How can proteins be used to form ACoA?

A

Via proteolysis which breaks them down to amino acids.

The amino acids can be broken down by oxidative de-amination to ACoA.

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58
Q

What other names can the TCA cycle be referred to as?

A

The tricarboxylic acid cycle (TCA cycle).

The krebs cycle.

The citrate cycle.

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59
Q

Where does the TCA cycle occur?

A

In the mitochondrial matrix.

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60
Q

What happens in the 1st step of the TCA cycle?

A

ACoA is added to oxaloacetate which creates a molecule called citrate.

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61
Q

How many carbons does oxaloacetate have?

A

4.

62
Q

How many carbons does citrate have?

A

6.

63
Q

How many steps are in the TCA cycle?

A

8.

64
Q

What is the final product of the TCA cycle?

A

Citrate allowing the whole cycle to repeat itself.

65
Q

How many carbons are lost from citrate in the TCA cycle?

A

2.

66
Q

How much energy is generated by the TCA cycle per ACoA?

A

3 NADH = 9 ATP.
1 GTP = 1 ATP.
1 FADH2 = 2 ATP.

Total = 12 ATP.

67
Q

How much energy is generated by the TCA cycle per glucose molecule?

A

6 NADH = 12 ATP.
2 GTP = 2 ATP.
2 FADH2 = 4 ATP.

Total = 24 ATP.

68
Q

How many times does the TCA cycle turn per glucose molecule?

A

2.

69
Q

What happens at step 1 of the TCA cycle?

A

Acetyl CoA combines with oxaloacetate to form citrate.

A water molecule will then remove CoA.

70
Q

What enzyme is involved in step 1 of the TCA cycle?

A

Citrate synthase.

71
Q

What happens at step 2 of the TCA cycle?

A

An isomerisation reaction takes place and an isocitrate is formed.

72
Q

What happens in the isomerisation of citrate in step 2 of the TCA cycle?

A

An OH is moved from carbon 3 to carbon 4.

The acetyl group is lost as CO2.

73
Q

What enzyme is involved in step 2 of the TCA cycle?

A

Acontinase.

74
Q

What happens at step 3 of the TCA cycle?

A

Isocitrate is de-carboxylated and the 1st CO2 molecule is removed to form alpha-ketogluterate.

75
Q

How many carbons does alpha-ketogluterate have?

A

5.

76
Q

Is any energy produced in step 3 of the TCA cycle?

A

1 NADH.

77
Q

What happens at step 4 of the TCA cycle?

A

α-ketogluterate loses a CO2 molecule and COA is added in its place.

This forms succinyl CoA and NADH.

AKDH is similar to pyruvate dehydrogenase as it requires the same 5 coenzymes.

78
Q

How many carbons does succinyl CoA have?

A

4 carbons bound to CoA.

79
Q

What enzyme is used in step 4 of the TCA cycle?

A

Alpha-ketoglutarate dehydrogenase.

80
Q

Is any energy produced in step 4 of the TCA cycle?

A

1 NADH.

81
Q

What happens at step 5 of the TCA cycle?

A

The high energy bond between succinyl and CoA is broken to form succinate.

82
Q

Is any energy produced in step 5 of the TCA cycle?

A

1 GTP.

83
Q

What enzyme is used in step 5 of the TCA cycle?

A

Succinyl CoA synthetase (succinate thiokinase).

84
Q

What happens at step 6 of the TCA cycle?

A

2H atoms are oxidised and removed from succinate to form fumarate.

85
Q

When succinate is converted to fumarate by succinate dehydrogenase, what will replace the 2 H atoms that are lost from succinate?

A

A double bond is formed within succinate to compensate for the loss of the 2 H atoms

86
Q

What enzyme is used in step 6 of the TCA cycle?

A

Succinate dehydrogenase.

87
Q

Is any energy produced in step 6 of the TCA cycle?

A

1 FADH2.

88
Q

What happens at step 7 of the TCA cycle?

A

A water molecule is added to fumarate by a hydrolase to create L-malate.

89
Q

How does fumarase change fumarate to malate?

A

It adds an OH and an H to carbons on either side of the double bond.

This removes the double bond that was formed in the previous step.

90
Q

What enzyme is used in step 7 of the TCA cycle?

A

Fumarase.

91
Q

What happens at step 8 of the TCA cycle?

A

L-malate is oxidised to oxaloacetate.

92
Q

Is any energy produced in step 8 of the TCA cycle?

A

1 NADH.

93
Q

What enzyme is used in step 8 of the TCA cycle?

A

Malate dehydrogenase.

94
Q

What happens to the oxaloacetate that is formed is step 8 of the TCA cycle?

A

It is re-entered into the TCA cycle.

95
Q

What steps of the TCA cycle produce energy?

A

Step 3.

Step 4.

Step 5.

Step 6.

Step 8.

96
Q

What is produced by the isocitrate dehydrogenase step in the TCA cycle?

A

1 NADH.

1 CO2.

97
Q

What is produced by the alpha keto-gluterate de-hydrogenase step in the TCA cycle?

A

1 NADH.

1 CO2.

98
Q

What is produced by the succinyl CoA synthase step in the TCA cycle?

A

1 GTP.

99
Q

What is produced by the succinate dehydrogenase step in the TCA cycle?

A

1 FADH2.

100
Q

What is produced by the malate dehydrogenase step in the TCA cycle?

A

1 NADH.

101
Q

How much ATP is generated by 1 turn of the TCA cycle?

A

12 ATP.

102
Q

What are the 4 regulated enzymes in the TCA cycle?

A

Citrate synthase.

Isocitrate dehydrogenase.

Alpha KG dehydrogenase.

Succinate dehydrogenase.

103
Q

In general, what kind of molecules will regulate the enzymes in the TCA cycle?

A

High energy molecules.

NADH.

ATP.

104
Q

What is citrate synthase activated by?

A

Substrate availability.

ADP.

Calcium.

105
Q

What is citrate synthase regulated by?

A

Fatty acyl CoA.

ATP.

NADH.

Succinly CoA.

106
Q

What is isocitrate dehydrogenase activated by?

A

Calcium.

ADP.

107
Q

What is isocitrate dehydrogenase regulated by?

A

ATP.

NADH.

108
Q

What is alpha-KG dehydrogenase activated by?

A

Calcium.

109
Q

What is alpha-KG dehydrogenase regulated by?

A

ATP.

GTP.

NADH.

Succinly CoA.

110
Q

What is succinate dehydrogenase activated by?

A

ADP.

Succinate.

Phosphate.

111
Q

What is succinate dehydrogenase regulated by?

A

Oxaloacetate.

112
Q

What can citrate inhibit in glycolysis?

A

PFK-1 in step 3.

113
Q

Citrate can be used as a pre-cursor for what?

A

Fatty acid and sterol synthesis.

114
Q

How much ATP is produced via the aerobic respiration of 1 glucose molecule?

A

36-38 molecules of ATP produced per glucose molecule.

115
Q

What can influence the final amount of ATP that is generated by aerobic respiration?

A

The use of different shuttles will determine whether 36 or 38 ATPs are generated.

116
Q

How much CO2 is generated by glycolysis?

A

0.

117
Q

How much CO2 is generated in the PDH complex?

A

0.

118
Q

How much CO2 is generated in the TCA cycle?

A

1 turn = 2.

2 turns = 4.

119
Q

How much NADH is generated by glycolysis?

A

2.

120
Q

How much NADH is generated in the PDH complex?

A

2.

121
Q

How much NADH is generated in the TCA cycle?

A

6 = 2 turns.

3 = 1 turn.

122
Q

1 NADH gives how much ATP?

A

3 ATPs.

123
Q

How much ATP is generated by NADH production in glycolysis?

A

6.

124
Q

How much ATP is generated by NADH production in PDH complex?

A

6.

125
Q

How much ATP is generated by NADH production in the TCA cycle?

A

9 = 1 turn.

18 = 2 turns.

126
Q

How much FADH2 is generated by glycolysis?

A

0.

127
Q

How much FADH2 is generated in the PDH complex?

A

0.

128
Q

How much FADH2 is generated in the TCA cycle?

A

1 = 1 turn.

2 = 2 turns.

129
Q

FADH2 is worth how many ATPs?

A

2 ATPs.

130
Q

How much ATP is generated by FADH2 production in the TCA cycle?

A

1 turn = 2 ATP.

2 turns = 4 ATP.

131
Q

How much GTP is generated by glycolysis?

A

0.

132
Q

How much GTP is generated in the PDH complex?

A

0.

133
Q

How much GTP is generated in the TCA cycle?

A

1 = 1 turn.

2 = 2 turns.

134
Q

GTP is worth how many ATPs?

A

1.

135
Q

How much ATP is generated by substrate level phosphorylation in glycolysis?

A

2.

136
Q

How much ATP is generated by substrate level phosphorylation in the PDH complex?

A

0.

137
Q

How much ATP is generated by substrate level phosphorylation in the TCA cycle?

A

1 turn = 1.

2 turns = 2.

138
Q

What is the maximum ATP yield of glycolysis?

A

8 ATP.

139
Q

What is the maximum ATP yield of the PDH complex?

A

6 ATP.

140
Q

What is the maximum ATP yield of the TCA cycle?

A

24 ATP.

141
Q

What are the clinical features of a PDH deficiency?

A

Lactic acidosis.

Neurological defects.

Myopathy.

Death.

142
Q

How will an inherited deficiency in the PDH complex cause lactic acidosis?

A

Pyruvate cannot be converted to ACoA and will result in a build up of pyruvate molecules in the mitochondria.

The body converts pyruvate to lactate and alanine.

This will cause lactic acidosis.

143
Q

What is the major problem with a PDH deficiency?

A

If pyruvate cannot be converted to lactate then the body is missing out on most of its energy.

144
Q

Is a PDH deficiency usually fatal?

A

Yes.

145
Q

How will a thiamine deficiency affect ATP output?

A

It will decrease it.

146
Q

What are the clinical features of a thiamine deficiency?

A

Ataxia.

Ophthalmolplagia.

Memory loss.

Cerebral haemorrhage.

147
Q

Where is the vitamin thiamine used?

A

In the PDH complex.

148
Q

What is the most common co-enzyme deficiency in the PDH complex?

A

Thiamine.

149
Q

What is another name for a thiamine deficiency?

A

Werneke-Korsakoff syndrome.

150
Q

What kind of people are most likely to have a thiamine deficiency?

A

Alcoholics and malnourished individuals.

151
Q

Is thiamine used as a co-enzyme in any other enzymes?

A

Thiamine is also required for alpha-KG which is used in the TCA cycle.