21 - Citric Acid Cycle Flashcards

1
Q

What is the final part of the oxidation of nutrients to CO2?

A

The citric acid cycle

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2
Q

True or false? All nutrients can somehow be broken down to acetyl-CoA?

A

True

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3
Q

The citric acid cycle oxidizes acetyl-CoA to _____ and reduces NAD+ and FAD to _____ and ____

A

Acetyl-CoA oxidized to CO2

NAD and FAD reduced to NADH and FADH2

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4
Q

What fuels aerobic ATP generation?

A

The energy from the electron chain oxidizing NADH and FADH2 (they donate their electrons to the ETC), reducing oxygen to water.

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5
Q

What is the equation for oxidative phosphorylation?

A

O2 + NADH + H+ -> H2O + NAD+

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6
Q

True or false? The conversion of nutrients (fatty acids, glycerol, glucose, amino acids) to pyruvate and/or Acetyl-CoA is reversible?

A

True

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7
Q

What three types of nutrients can make pyruvate (which can then be made into Acetyl-CoA)?

A

Glycerol, glucose and amino acids

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8
Q

Which two enzymes can be made directly into Acetyl-CoA?

A

Fatty acids and amino acids

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9
Q

Where does the citric acid cycle take place?

A

mitochondria

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10
Q

Why does the citric acid cycle not take place in red blood cells?

A

They don’t have mitochondria, which is where the TCA takes place

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11
Q

True or false? ALL metabolites needed for the citric acid cycle must be imported into the mitochondria?

A

True

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12
Q

What does a more positive E° (standard reduction potential) indicate?

A

Higher affinity for electrons

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13
Q

With regards to E°, when is a reaction involving half reactions spontaneous?

A

When the half reactions add to make a positive E°

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14
Q

The a full reaction (with a combinatino of half reactions), in what direction to electrons flow (with regards to E°)?

A

Flow spontaneously from the species with more negative E° to more positive E°

The positive partner is reduced
The negative partner reduces the positive partner

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15
Q

What are the two redox coenzymes that are forms of nicotinic acid?

A

Nicotinamide adenine dinucleotide (NADH)

Nicotinamide adenine dinucleotide phosphate (NADPH)

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16
Q

What are the two coenzymes that are forms of riboflavin (vitamin B2)? (Flavin coenzymes)

A

Flavin mononucleotide (FMN)

Flavin adenine dinucleotide (FAD) - tightly bound in flavoproteins

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17
Q

What is the number of carbon atoms in the reaction intermediates of TCA, starting at the condensation of acetyl CoA and oxaloacetate? What products coe out with each oxidative decarboxylation?

A

C4 (oxaloacetate) + C2 (Acetyl CoA) = C6 = C5 + NADH + CO2 = C4 + NADH + CO2 = C4 (oxaloacetate) + ATP + FADH2 + NADH

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18
Q

What enzyme converts pyruvate to acetyl CoA?

A

Pyruvate dehydrogenase

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19
Q

(TCA cycle) What enzyme converts acetyl CoA to citrate? What is required?

A

Citrate synthase, oxaloacetate is required to start the reaction.

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20
Q

(TCA cycle) What enzyme converts citrate to isocitrate?

A

Aconitase

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21
Q

(TCA cycle) True or false? Redox reactions always require to half reactions.

A

True, one to be reduced and one to be oxidized

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22
Q

(TCA cycle) What reaction starts the citric acid cycle?

A

C2 (Acetyl-CoA) and C4 (Oxaloacetate)

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23
Q

How many times does the citric acid cycle run for one glucose?

A

Twice

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24
Q

Is the oxidation of pyruvate to acetyl-CoA reversible?

A

no

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25
Q

(TCA cycle) What enzyme converts isocitrate to α-ketoglutarate? What is required?

A

isocitrate dehydrogenase, NAD+ is reduced to NADH, forming CO2 in the process

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26
Q

(TCA cycle) What enzyme converts α-ketoglutarate to Succinyl-CoA? What is required?

A

Ketoglutarate dehydrogenase, NAD+ is reduced to NADH and CO2 is produced

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27
Q

(TCA cycle) What enzyme converts Succinyl-CoA to Succinate? What is required?

A

Succinyl-CoA synthetase, ADP is phosphorylated to ATP

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28
Q

(TCA cycle) What enzyme converts succinate to fumarate? What is required?

A

Succinate dehydrogenase, FAD is reduced to FADH2

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29
Q

(TCA cycle) What enzyme converts fumarate to malate?

A

Fumarase

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30
Q

(TCA cycle) What enzyme converts malate to oxaloacetate? What is required?

A

Malate dehydrogenase, NAD+ is reduced to NADH

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31
Q

What are the six requirements for the oxidation of pyruvate to acetyl CoA (excluding pyruvate itself)?

A
Pyruvate dehydrogenase
NAD+
FAD
TPP
Coenzme A (CoA-SH)
Lipoic acid
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32
Q

What is NAD+ derived from?

A

Niacin (vitamin B3)

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33
Q

What is TPP (thiamine pyrophosphate) derived from?

A

thiamine (vitamin B1)

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34
Q

What is FAD derived from?

A

Riboflavin (vitamin B2)

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35
Q

What is Coenzyme A (CoA-SH) derived form?

A

pantothenic acid (vitamin B5)

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36
Q

What are the two components of coenzyme A? Via what type of bond?

A

An ADP linked to a phosphopantetheine via phosphate ester bond between the pantothenic acid part of phosphopantetheine

37
Q

What are two componenets of phosphopantetheine (linked to ADP to form coenzyme A). What makes it the reactive part of coenzyme A?

A

Mercaptoethylamine and pantothenic acid

Mercaptoethylamine contains an SH (thiol) group, which is the reactive part in CoASH

The thiol group can form thioester bonds, which are more reactive than carboxyesters, which means coenzyme A can transfer acyl groups

38
Q

What is the difference between CoASH and CoA?

A

CoASH is coenzyme A with a thiol group, CoA is coenzyme A when bound to something

39
Q

What is acetyl-CoA?

A

Acetyl-coenzyme A is a coenzyme A with a thioester bond to acetate

40
Q

What is the thioester of coenzyme A and acetic acid?

A

Acetyl-CoA

41
Q

What is the activated form of acetate?

A

Acetyl-CoA

42
Q

What is a metabolic hub that serves as a precursor for many larger metabolites?

A

Acetyl-CoA

43
Q

The conversion of pyruvate to acetyl CoA requires how many steps?

A

5 consecutive reactions catalyzed by five enzymes in a large complex (pyruvate dehydrogenase)

44
Q

What are the 6 steps of the conversion of pyruvate to acetyl CoA?

A
  1. Pyruvate is attacked by TPP, the reaction is catalyzed by pyruvate decarboxylase (pyruvate dehydrogenase E1)
  2. A CO2 is ejected and pyruvate decarboxylase catalyses another decarboxylation, forming hydroxyethyl-TPP (intermediate)
  3. Hydroxyethyl-TPP attacks lipoamide cofactor (redox active), catalyzed by Dihydrolipoyl transacetylase
  4. Generation of acetyl lipoamide and regeneration of TPP from intermediate of dihydrolipoyl transacetylase reaction
  5. Release of acetyl-CoA from acetyl lipoamide
  6. Regeneration of lipoamide by dihydrolipoyl dehydrogenase
45
Q

How is PDH (pyruvate dehydrogenase) regulated?

A

It is allosterically inhibited by acetyl-CoA and NADH (product inhibition)

46
Q

What causes PDH (pyruvate dehydrogenase) to be activated?

A

The dephosphorylation of PDH-phospho (inactive) to PDH by PDH phosphatase (replaces phosphate with H2O)

47
Q

What causes PDH (pyruvate dehydrogenase to become inactive)?

A

PDH kinase phosphorylates PDH (active) to make it PDH-phospho (inactive) using ATP

48
Q

What is the second level of regulation of PDH (pyruvate dehydrogenase)?

A

Allosteric regulation of PDH kinase

49
Q

What activates PDH kinase?

A

Acetyl-CoA

50
Q

What inhibits PDH Kinase?

A

Pyruvate
ADP
Calcium ion (and high Mg)]
Potassium ion

51
Q

What are the 6 steps of the citric acid cycle?

A
  1. Citrate synthase - condensation of oxaloacetate with acetyl-CoA to citrate
  2. Aconitase - Isomerization of citrate to isocitrate by dehydration - hydration
  3. Isocitrate dehydrogenase - oxidative decarboxylation of isocitrate to α-ketoglutarate
  4. α-ketoglutarate dehydrogenase complex - oxidative decarboxylation to succinyl-CoA, similar to PDH complex
  5. Succinyl-CoA synthetase - Hydrolysis of CoA ester generates succinate and ATP or GTP
  6. Succinate dehydrogenase, fumarase, malate dehydrogenase - regeneration of oxaloacetate by oxidation of succinate
52
Q

What goes into the citric acid cycle (stoichiometrically accurate)?

A
1 Acetyl CoA 
3 NAD+
1 FAD
1 GDP
1 Pi
2 H2O
53
Q

What comes out of the citric acid cycle (stoichiometrically accurate)?

A
2 CO2
3 NADH
1 FADH2
1 GTP
1 CoASH
2 H+
54
Q

How many electron pairs does CoA yield? Where are these allocated in the TCA cycle?

A

Acetyl CoA (4 electron pairs)

  • 3 into NADH
  • 1 into FADH2
55
Q

How many NADH and FADH2 enter the electron transport chain?

A

3 NADH

1 FADH2

56
Q

How many molecules of O2 are reduced to H2O from the 3 NADH and 1 FADH that enter the electron transport chain?

A

2 molecules of O2

57
Q

Each NADH yields energy for approximately how many ATP?

A

3 ATP

58
Q

Each FADH2 yields energy for how many ATP?

A

2 ATP

59
Q

Each turn of the citric acid cycle makes how much ATP?

A

About 11 ATP and 1 GTP = 12 ATP

60
Q

How many acetyl-CoA does one glucose yield?

A

2

61
Q

What is aerobic metabolism?

A

NADH and FADH2 fueling ATP generation by oxidative phosphorylation when there is sufficient oxygen

62
Q

What is the total amount of ATP that can be made from aerobic respiration?

A

32 ATP

3 ATP from from 2 FADH2
25 ATP from 10 NADH
2 ATP from glycolysis
2 ATP from TCA cycle

63
Q

How many NADH/FADH2 are made from glycolysis?

A

2 NADH

0 FADH2

64
Q

How many NADH/FADH2 are made from pyruvate dehydrogenase complex?

A

2 NADH

0 FADH2

65
Q

How many NADH/FADH2 are made from TCA cycle?

A

6 NADH

2 FADH2

66
Q

How much ATP is made from anaerobic respiration?

A

2 ATP from glycolysis

67
Q

What are the net reactants of aerobic respiration?

A
1 Glucose
10 NAD+
2 FAD
2 H2O
4 ADP
4 Pi
68
Q

What are the net products of aerobic respiration?

A
6 CO2
10 NADH
4 H+
2 FADH2
4 ATP

(the reduction of NADH and FADH2 yields a further 28 ATP)

69
Q

What three things module the regulation of the citric acid cycle?

A

Substrate availability
Product inhibition
Inhibition by other cycle intermediates

70
Q

What inhibits the conversion of isocitrate to α-ketoglutarate?

A

ATP and NADH

71
Q

What increases the conversion of isocitrate to α-ketoglutarate?

A

ADP

72
Q

What inhibits the conversion of α-ketoglutarate to succinyl CoA?

A

ATP
succinyl CoA
NADH

73
Q

The citric acid cycle is regulated by the coordination of what four things?

A
  • Need for ATP
  • Glycolysis
  • Electron transport/oxidative phosphorylation
  • Use of citrate
74
Q

Activity of TCA cycle depends on (6 things)

A
  • Substrate availability
  • Product inhibition
  • Inhibition by other cycle intermediates
  • Availability of intermediates (more intermediates = more reactions at the same time)
  • Electron transport chain/oxidative phosphorylation to regenerate NAD+ and FAD
  • Availability of oxygen
75
Q

What are cataplerotic reactions in TCA cycle?

A

They drain the TCA cycle by using intermediates in the TCA cycle as precursors for anabolic reactions

76
Q

What are anaplerotic reactions in TCA cycle?

A

They fill up the citric acid cycle by providing intermediates of TCA cycle.

77
Q

The citric acid cycle is amphibolic, meaning?

A

It is catabolic and anabolic.

78
Q

What are the four cataplerotic reactions of TCA cycle?

A
  • Citrate to fatty acids
  • Citrate to cholesterol
  • Succinyl-CoA to poryphyrins
  • Malate to glucose
79
Q

What are 5 anaplerotic reactions of TCA cycle?

A
  • CO2 to oxaloacetate
  • Pyruvate to oxaloacetate
  • Asparate phenylalanine tryosine to fumarate
  • isoleucine methionine valine to succinyl-CoA
  • Odd-chain fatty acids to succinyl-CoA
80
Q

What happens to citrate when it is exported from mitochondria?

A

It is converted to acetyl-CoA, which is used for fatty acid and cholesterol synthesis

81
Q

What things can be transported into mitochondria to make succinyl-CoA?

A

Odd chain fatty acids

Some amino acids

82
Q

Ketoglutarate can be interconverted with what?

A

Ketoglutarate can be interconverted with glutamate

83
Q

Oxaloacetate is a precursor for what in the liver? It can be converted to what?

A

Glucose synthesis (gluconeogenesis) in the liver.Can be converted to aspartate for protein synthesis and breakdown.

84
Q

What enzyme does acetyl-CoA stimulate to convert pyruvate (to what?)

A

Pyruvate carboxylase, converts pyruvate to oxaloacetate

85
Q

Acetyl-CoA inhibits PDH, which converts pyruvate to what?

A

Acetyl-CoA

86
Q

If there is an overabundance of acetyl-CoA (eg. due to fatty acid breakdown), what will happen to pyruvate?

A

Pyruvate will be converted to oxaloacetate to provide enough TCA cycle intermediates to use the Acetyl-CoA

87
Q

What saves glucose from TCA cycle when energy can come from fat?

A

Acetyl-CoA inhibition of PDH and stimulation of PC (pyruvate carboxylase)

88
Q

What is the PDH complex composed of?

A

3 enzymes in one,

Pyruvate dehydrogenase (E1)
Dihydrolipoyl transacetylase (E2)
Dihydrolipoyl dehydrogenase (E3)
89
Q

What are the 5 reactions catalyzed by the PDH complex?

A
  1. Pyruvate is decarboxylated (loses CO2) and forms hydroxyethyl TTP (no redox)
  2. Hydroxyethyl group is transferred to lipoic acid and oxidized to form acetyl dihydrolipoamide (dehydrogenase reaction, redox: hydroxyethyl group is oxidized, lipoamide is reduced)
  3. Acetyl group is transferred to CoA
  4. Dihydrolipoamide is reoxidized, which is linked to the reduction of NAD+ in reaction 5