Brainscape's Knowledge GenomeTM

Browse over 1 million classes created by top students, professors, publishers, and experts.


See full index

Biochemistry > Chapter 17- The citric acid cycle > Flashcards

Chapter 17- The citric acid cycle Flashcards

1
Q

What is the main entry point to the citric acid cycle?

A

Acetyl CoA

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

Acetyl CoA function

A

Under aerobic conditions, pyruvate enters the mitochondria where it is converted into acetyl CoA. Acetyl CoA is the fuel for the citric acid cycle.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

Citric acid cycle

A

Processes the two-carbon acetyl unit to two molecules of CO2 while harvesting high-energy electrons that can be used to form ATP. A key function of the citric acid cycle is to harvest high-energy electrons in the form of NADH and FADH2

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

How are high energy electrons harvested in the citric acid cycle?

A

The two-carbon acetyl unit from acetyl CoA condenses with oxaloacetate to form citrate, which is subsequently oxidized

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

What are high energy electrons used for in the electron transport chain?

A

The high-energy electrons are used later in the electron transport chain and eventually reduce O2 to H2O. During the passage of electrons through the transport chain, proton pumps generate a proton gradient that is used to synthesize ATP.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

Pyruvate dehydrogenase complex

A

The pyruvate dehydrogenase complex, a component of the mitochondrial matrix, is composed of three distinct enzymes that oxidatively decarboxylate pyruvate to form acetyl CoA. This reaction is an irreversible link between glycolysis and the citric acid cycle.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

The synthesis of acetyl CoA requires

A

3 enzymes and 5 coenzymes (catalytic and stochiometric cofactors).

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

Catalytic cofactors (3)

A
  1. Thiamine pyrophosphate
  2. Lipoic acid
  3. FAD
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

Stochiometric cofactors (2)

A
  1. CoA
  2. NAD+
    Stochiometric cofactors are cofactors that function as substrates
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

Substrate

A

The substance on which an enzyme acts

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

Steps of the synthesis of acetyl CoA from pyruvate (3)

A

A decarboxylation, an oxidation, and the transfer of an acetyl unit to CoA

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

Why must the steps of the synthesis of acetyl CoA from pyruvate be coupled?

A

The steps must be coupled to preserve the free energy derived from the decarboxylation step, since this drives the formation of NADH and acetyl CoA

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

How is the decarboxylation in the synthesis of acetyl CoA catalyzed?

A

The first step in the reaction that is catalyzed by the pyruvate dehydrogenase complex is the decarboxylation. Pyruvate dehydrogenase (E1), a component of the complex, catalyzes the decarboxylation. Pyruvate combines with the ionized form of the coenzyme thiamine pyrophosphate (TPP).

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

Mechanism of decarboxylation (4 steps)

A
  1. TPP forms a carbanion.
  2. The carbanion attacks the carbonyl group of pyruvate.
  3. Decarboxylation occurs. The positive charge on the TPP stabilizes the negative charge resulting from the decarboxylation.
  4. Protonation occurs to yield the hydroxyethyl-TPP intermediate.
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

How does oxidation in the synthesis of acetyl CoA occur?

A

The second step in the reaction that is catalyzed by the pyruvate dehydrogenase complex is the oxidation. The two-carbon fragment is oxidized and transferred to dihydrolipoamide to form acetyllipoamide on E2 in a reaction also catalyzed by E1

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

How does the linkage to acetyl CoA occur?

A

E2 catalyzes the transfer of the acetyl group from acetyllipoamide to coenzyme A to form acetyl CoA.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
17
Q

How does the regeneration of oxidized lipoamide occur in the synthesis of acetyl CoA?

A

To participate in another reaction cycle, dihydrolipoamide must be reoxidized. This reaction is catalyzed by dihydrolipoyl dehydrogenase (E3), and it also regenerates NADH

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
18
Q

Dihydrolipoamide is formed by

A

The attachment of the vitamin lipoic acid to a lysine residue in dihydrolipoyl transacetylase (E2)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
19
Q

The core of the pyruvate dehydrogenase complex is formed by

A

60 molecules of E2, the transacetylase.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
20
Q

Why are the enzymes of the pyruvate dehydrogenase complex structurally integrated?

A

The three enzymes of the pyruvate dehydrogenase complex are
structurally integrated, and the lipoamide arm allows rapid movement of substrates and products from one active site of the complex to another.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
21
Q

Steps in the pyruvate dehydrogenase mechanism (6)

A
  1. Pyruvate is decarboxylated at the active site of E1, forming the
    hydroxyethyl-TPP intermediate. CO2 leaves as the first product.
  2. E2 inserts the lipoamide arm of the lipoamide domain into the deep channel in E1 leading to the active site.
  3. E1 catalyzes the transfer of the acetyl group to the lipoamide. The acetylated arm then leaves E1 and enters the E2 cube to visit the active site of E2, located deep in the cube at the subunit interface.
  4. The acetyl group is then transferred to CoA, and the second product, acetyl CoA, leaves. The reduced lipoamide arm then swings to the active site of E3.
  5. At the E3 active site, the lipoamide is oxidized by FAD. The reactivated lipoamide is ready to begin another reaction cycle.
  6. The final product, NADH, is produced with the reoxidation of FADH2
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
22
Q

Citrate synthase

A

Catalyzes the condensation of acetyl CoA and oxaloacetate to form citrate. The enzyme is referred to as a synthase since it joins two units without direct participation of an NTP.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
23
Q

Which molecule is first formed in the citric acid cycle?

A

Citryl CoA is first formed. The favorable hydrolysis of the thioester to release CoA drives what would otherwise be a relatively unfavorable lengthening of the carbon chain

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
24
Q

How does the mechanism of citrate synthase prevent undesirable reactions?

A

Citrate synthase exhibits induced fit, since oxaloacetate binding induces structural changes in the enzyme that lead to the formation of the acetyl CoA binding site. This also indicates that it is an example of “ordered sequential” kinetics

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
25
Q

Citryl CoA function

A

The formation of the reaction intermediate citryl CoA causes a dramatic structural change that completes active site formation, enabling cleavage of the thioester linkage. Citryl CoA is then cleaved to form citrate and CoA.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
26
Q

Aconitase

A

An iron–sulfur protein (also referred to as a non-heme iron protein) that catalyzes the formation of isocitrate from citrate. It catalyzes a dehydration followed by a hydration.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
27
Q

Isocitrate dehydrogenase

A

Catalyzes the oxidative decarboxylation of isocitrate, forming α-ketoglutarate and capturing high-energy electrons as NADH. The first of two CO2 molecules released in the citric acid cycle is produced here.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
28
Q

α-ketoglutarate dehydrogenase complex

A

Catalyzes the synthesis of succinyl CoA from α-ketoglutarate, generating another molecule of NADH.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
29
Q

Succinyl coenzyme A is formed by

A

The oxidative decarboxylation of alpha-ketoglutarate

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
30
Q

Succinyl CoA synthetase

A

Catalyzes the cleavage of a thioester linkage and concomitantly forms ATP. The formation of ATP by succinyl CoA synthetase is an
example of a substrate-level phosphorylation because succinyl phosphate, a high phosphoryl-transfer potential compound, donates a phosphate to ADP.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
31
Q

Where does the the ADP-requiring isozyme of succinyl coenzyme A
predominate?

A

In tissues that perform large amounts of cellular respiration (e.g., skeletal and heart muscle), the ADP-requiring isozyme predominates

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
32
Q

Where does the the GDP-requiring isozyme of succinyl coenzyme A
predominate?

A

In tissues that perform large amounts of cellular respiration (e.g., skeletal and heart muscle), the ADP-requiring isozyme predominates. In tissues that perform many anabolic reactions (e.g., liver), the GDP-requiring enzyme is common and can work in reverse so that GTP is used to power succinyl CoA synthesis. Succinyl CoA is then used in heme synthesis

33
Q

Succinyl coenzyme A synthetase-catalyzed reaction steps (4)

A
  1. Phosphate attacks succinyl CoA, displacing the CoA and
    forming succinyl phosphate, a molecule with high
    phosphoryl-transfer potential.
  2. Histidine removes the phosphoryl group, forming
    phosphohistidine and succinate.
  3. The phosphohistidine reorients to approach the bound
    ADP.
  4. The phosphoryl group is transferred to ADP to form ATP.
34
Q

How is oxaloacetate regenerated?

A

Succinate dehydrogenase, fumarase, and malate dehydrogenase catalyze successive reactions to regenerate oxaloacetate. FADH2 and NADH are generated. Oxaloacetate can condense with another acetyl CoA to initiate another cycle.

35
Q

Succinate dehydrogenase

A

Succinate dehydrogenase is associated with the electron transport chain. The electrons pass directly from FADH2 to coenzyme Q. The acceptor needs to be FAD, because the free energy change for this reaction would have been insufficient to reduce NAD+

36
Q

Malate dehydrogenase

A

Catalyzes the stereospecific addition of H+ and OH−, yielding only the L-isomer of malate

37
Q

What occurs in the final step of the oxidation of succinate?

A

In the final step, malate is oxidized to oxaloacetate, producing another molecule of NADH. This reaction is extremely endergonic under standard conditions. The actual ΔG becomes favorable because of the use of the products: oxaloacetate in the first step of the citric acid cycle and NADH in the electron transport chain

38
Q

Each pair of electrons from NADH will generate

A

2.5 ATP when used to reduce oxygen in the electron-transport chain

39
Q

Each pair of electrons from FADH2 will power

A

The synthesis of ~1.5 ATP with the reduction of oxygen in the electron-transport chain.

40
Q

Substrate channeling

A

Unlike glycolysis, which has anaerobic strategies (fermentation) for replenishing NAD+ if needed, the citric acid cycle can only proceed if there is enough O2 for the electron transport chain to proceed, using NADH and FADH2 and releasing the oxidized form of these carriers.

41
Q

Which characteristic of the citric acid cycle allows for substrate channeling?

A

Evidence suggests that there is a physical association of all of the enzymes of the citric acid cycle into a supramolecular complex. This close arrangement of enzymes enhances the efficiency of the citric acid cycle by the strategy of substrate channeling

42
Q

Function of the supramolecular complex

A

Evidence suggests that there is a physical association of all of the enzymes of the citric acid cycle into a supramolecular complex. The close arrangement of enzymes enhances the efficiency of the citric acid cycle because a reaction product can pass directly from one
active site to the next through connecting channels

43
Q

Citric acid cycle reactants (2)

A
  1. Two carbon atoms enter in the form of an acetyl unit

2. Two water molecules are consumed

44
Q

When is each water molecule consumed in the citric acid cycle?

A

One in the synthesis of citrate by the hydrolysis of citryl CoA and the other in the hydration of fumarate

45
Q

Citric acid cycle products (3)

A
  1. Two carbons leave in the form of CO2 molecules (though isotope labeling studies indicate that they are not the same carbon atoms that immediately leave).
  2. Four pairs of electrons leave on the reduced form of electron carriers (three NADH and one FADH2)
  3. One NTP (usually ATP) is generated
46
Q

Is the formation of acetyl CoA reversible?

A

The formation of acetyl CoA from pyruvate is irreversible in animal cells

47
Q

2 main fates of acetyl CoA

A

Metabolism by the citric acid cycle or incorporation into fatty acids.

48
Q

Why must the pyruvate dehydrogenase complex be regulated?

A

The pyruvate dehydrogenase complex must be carefully regulated in order to meet the cell’s needs. The regulatory strategies include both allosteric regulation and reversible phosphorylation.

49
Q

How does PDK regulate the pyruvate dehydrogenase complex?

A

The key means of regulating the complex is covalent modification. The kinase pyruvate dehydrogenase kinase (PDK), which in mammals is associated with the complex, phosphorylates and inactivates the complex

50
Q

How does PDP regulate the pyruvate dehydrogenase complex?

A

The phosphatase pyruvate dehydrogenase phosphatase (PDP), also associated with the complex, removes the phosphate and reactivates the enzyme

51
Q

High ratios of which molecules inactivate the pyruvate dehydrogenase complex?

A

High ratios of NADH/NAD+, acetyl CoA/ CoA, and ATP/ADP
promote phosphorylation and inactivation of the complex by
activating PDK. This means that high concentrations of immediate (acetyl CoA and NADH) and ultimate (ATP) products inhibit the complex.

52
Q

Which molecules stimulate the pyruvate dehydrogenase complex?

A

High ADP and pyruvate stimulate the complex

53
Q

Pyruvate dehydrogenase phosphatase deficiency

A

Individuals with pyruvate dehydrogenase phosphatase deficiency have a pyruvate dehydrogenase complex that is always phosphorylated (i.e., inactive). In these individuals, glucose is processed to lactate rather than to acetyl CoA, and high blood lactic acid results. Many systems malfunction in the acidified environment,
particularly the central nervous system.

54
Q

What are the key control points of the citric acid cycle?

A

The key control points in the citric acid cycle are the reactions catalyzed by the allosteric enzymes isocitrate dehydrogenase and α-ketoglutarate dehydrogenase. These are the first two enzymes that harvest high-energy electrons in the cycle. Some aspects of the control of α-ketoglutarate dehydrogenase are similar to that of pyruvate dehydrogenase. Recall that these two are evolutionarily
related.

55
Q

Defects in which enzymes contribute to the development of cancer? (4)

A
  1. Succinate dehydrogenase
  2. Fumarase
  3. Pyruvate dehydrogenase kinase
  4. Isocitrate dehydrogenase
56
Q

How do defects in succinate dehydrogenase, fumarase, and pyruvate dehydrogenase kinase contribute to cancer development?

A

Mutations activate HIF-1, leading to enhanced aerobic glycolysis

57
Q

How do defects in isocitrate dehydrogenase contribute to cancer development?

A

Mutations result in the synthesis of 2-hydroxyglutarate, which modifies methylation patterns in DNA. These modifications can alter gene expression and promote rapid cell growth

58
Q

Acetyl CoA acetyltransferase

A

Synthesizes ketone bodies (e.g., acetoacetate), which serve as a fuel source for various tissues

59
Q

How do defects in acetyl CoA acetyltransferase contribute to cancer development?

A

In some cancers, the enzyme becomes phosphorylated, which changes its activity so that it acts as a protein acetyltransferase instead. It can then acetylate both pyruvate dehydrogenase and pyruvate dehydrogenase phosphatase. That acetylation inhibits those enzymes and facilitates the metabolic switch from oxidative
phosphorylation to aerobic glycolysis (known as the Warburg effect).

60
Q

Which general category of molecules is the citric acid cycle the source of?

A

Components of the citric acid cycle are precursors for biosynthesis of key biomolecules. As a major metabolic hub of the cell, the citric acid cycle integrates many of the cell’s other metabolic pathways, including those that involve the synthesis and degradation of carbohydrates, fats, amino acids, and other important molecules

61
Q

How is the citric acid cycle replenished?

A

Mammals lack the enzymes for the net conversion of acetyl CoA into oxaloacetate or any other citric acid cycle intermediate. Instead, oxaloacetate is formed by the carboxylation of pyruvate; this reaction is catalyzed by pyruvate carboxylase. Recall that this
reaction is also used in gluconeogenesis and is dependent on the
presence of acetyl CoA. This is an example of an anapleurotic reaction.

62
Q

Anapleurotic reaction

A

Filling up reaction- it replenishes the supply of a critical citric acid cycle intermediate

63
Q

Thiamine deficiency results in

A

Insufficient activity of pyruvate dehydrogenase and α-ketoglutarate
dehydrogenase, as well as an enzyme in the pentose phosphate pathway (transketolase). Thymine is the precursor of the cofactor thiamine pyrophosphate (TPP), and its absence prevents the functioning of those enzymes. The neurologic and cardiovascular disorder beriberi can result

64
Q

Where is thiamine found?

A

The vitamin thiamine is found in brown rice but not in white (polished) rice.

65
Q

Mercury and arsenite impair what process?

A

Pyruvate dehydrogenase complex activity

66
Q

How do mercury and arsenite impair pyruvate dehydrogenase complex activity?

A

Bind to the two sulfurs of dihydrolipoamide. 2, 3-Dimercaptopropanol can counter the effects of arsenite poisoning by forming a complex with the arsenite that can be excreted. Early hatters (hatmakers) used mercury to make felt, which inhibited
activity of the pyruvate dehydrogenase complex in the brain, often leading to strange behavior.

67
Q

Which pre-existing pathways could the citric acid cycle have evolved from?

A

Compounds such as pyruvate, α-ketoglutarate, and oxaloacetate were likely present early in evolution for biosynthetic purposes. The oxidative decarboxylation of these α-ketoacids is favorable thermodynamically and can be used to drive the synthesis of both acyl CoA derivatives and NADH.

68
Q

Glyoxylate cycle

A

The glyoxylate cycle is similar to the citric acid cycle but bypasses the two decarboxylation steps, allowing the synthesis of carbohydrates from fats. Succinate can be converted into oxaloacetate and then into glucose

69
Q

Where does the glyoxylate cycle occur?

A

Occurs in organelles called glyoxysomes, is prominent in oil-rich seeds such as sunflower seeds.

70
Q

What is the purpose of the glyoxylate cycle?

A

Enables plants and bacteria to grow on acetate

71
Q

What is diabetic neuropathy?

A

A numbness, tingling, or pain in the limbs and digits, it is a common
complication of both type 1 and type 2 diabetes

72
Q

What can cause diabetic neuropathy?

A

The symptoms may be caused by overproduction of lactic acid by cells in the dorsal root ganglion, a part of the nervous system responsible for pain perception. Lactate is a common fuel for neurons, which import the lactate and convert it to pyruvate for use in cellular respiration

73
Q

What causes the increase in lactic acid in diabetics?

A

May be due to hyperglycemia (high glucose), the defining feature of
diabetes. This increases pyruvate dehydrogenase kinase activity
in the cells of the dorsal root ganglion. This kinase then phosphorylates and inhibits the pyruvate dehydrogenase complex. Glycolytically produced pyruvate is then converted to lactate, and excess lactate leads to an increase in acid-sensing pain receptors

74
Q

How is mycobacterium tuberculosis transmitted?

A

The bacterium responsible for tuberculosis (TB), Mycobacterium tuberculosis, is transmitted by people with active lung infections by coughing and sneezing

75
Q

Why are new treatments necessary for tuberculosis?

A

A common treatment for TB is the antibiotic rifampicin, which acts as an inhibitor of bacterial protein translation. However, as resistant bacterial strains emerge, new treatments are needed

76
Q

How do tuberculosis bacteria replicate?

A

The bacteria are dependent on the glyoxylate cycle (which allows conversion of fats to glucose), especially when they are in a latent state in the lungs.

77
Q

Isocitrate lyase

A

A key enzyme in the glyoxylate cycle is isocitrate lyase. In the process of catalysis, a reactive thiolate is formed on cysteine 191 in the active site.

78
Q

How can a lyase inhibitor treat tuberculosis?

A

Because this cysteine is conserved in all M. tuberculosis strains, the
likelihood of evolving resistance is diminished.

Biochemistry (13 decks)

Brainscape helps you reach your goals faster, through stronger study habits.
© 2024 Bold Learning Solutions. Terms and Conditions