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2) Biochemistry II > Regulation of the TCA Cycle > Flashcards

Regulation of the TCA Cycle Flashcards

1
Q

Who first described the TCA cycle? Using what? What did he also contribute to?

A
  • Krebs
  • Using pigeon muscle
  • Urea cycle
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2
Q

What is the underlying premise of the TCA cycle?

A
  • Acetyl group of Acetyl-CoA is oxidized to CO2

- In the process, creates cellular respiration, energy released is conserved as NADH and FADH2

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3
Q

What is the most common input in the TCA cycle?

A
  • Most common: Acetyl CoA

- Some amino acids can yield other intermediates

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4
Q

What mechanisms yield Acetyl-CoA?

A
  • B-oxidation

- Amino acid catabolism (Leucine, threonine)

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5
Q

How many carbons does Acetyl-CoA contain? What about Pyruvate?

A
  • Acetyl-CoA: 2

- Pyruvate: 3

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6
Q

Which enzyme catalyzes the conversion of Pyruvate to Acetyl-CoA? What type of reaction is it?

A
  • Pyruvate Dehydrogenase Complex (PDC)

- IRREVERSIBLE oxidative decarboxylation

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7
Q

What is removed in the generation of Acetyl-CoA from Pyruvate?

A

Removal of hydrogen (oxidation) and removal of carbon (decarboxylation)

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8
Q

What is generated in the conversion of Pyruvate to Acetyl-CoA?

A

NADH

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9
Q

What is the composition of Coenzyme A?

A
  • Adenine + Ribose-phosphate: Phosphoadenosine diphosphate
  • Vitamin B5
  • Reactive thiol group (CoA-SH)
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10
Q

What is the first enzyme of PDC?

A

E1: Pyruvate dehydrogenase

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11
Q

What is the second enzyme of PDC?

A

E2: Dihydrolipoyl transacetylase

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12
Q

What is the third enzyme of PDC?

A

E3: Dihydrolipoyl dehydrogenase

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13
Q

What are the co-substrates of PDC?

A
  • CoA-SH

- NAD

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14
Q

What are the prosthetic groups of PDC?

A
  • Thiamine pyrophosphate (TPP)
  • Lipoate
  • FAD
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15
Q

Which B vitamin composes TPP?

A

Thiamine (B1)

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16
Q

Which B vitamin composes FAD?

A

Riboflavin (B2)

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17
Q

Which B vitamin composes NAD?

A

Niacin (B3)

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18
Q

Which B vitamin composes CoA?

A

Pantothenic acid (B5)

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19
Q

What happens in pyruvate dehydrogenase (E1)

A

1) Pyruvate attaches to TPP on E1, forming a hydroxyethal TPP
2) CO2 is removed

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20
Q

What happens in dihydrolipoyl transacetylase (E2)

A

1) Lipoate is attached to Lysine on E2, which forms a lipoyllysine
2) Lipoyllysine is acetylated (from its oxidized form) when the acetyl group of Pyruvate is transferred
3) Lipoyllysine is changed to its reduced form when the acetyl group is transferred to CoA, forming Acetyl-CoA

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21
Q

What happens in dihydrolipoyl dehydrogenase (E3)?

A

1) FADH2 produced is oxidized to FAD

2) NAD is reduced to NADH

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22
Q

Which compounds in PDC are permanently bound? What are they called?

A
  • Prosthetic groups

- TPP, lipoate, FAD

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23
Q

How many intermediates are there in the TCA cycle? How many enzymatic reactions?

A
  • 9 intermediates

- 8 enzymatic reactions

24
Q

How many carbons does oxaloacetate contain? What does it combine with to form citrate?

A
  • Oxaloacetate: 4C
  • Acetyl-CoA: 2C
  • Oxaloacetate + Acetyl-CoA = Citrate
25
Q

How many TCA cycle passes are needed to form CO2 from 2C of Acetyl-CoA? At which steps?

A
  • Steps 3 and 4

- 2 TCA cycle passes

26
Q

Which enzyme catalyzes the condensation step of the TCA cycle? What does it form? From what?

A
  • Enzyme: Citrate synthase

- Oxaloacetate + Acetyl-CoA = CItrate

27
Q

What does citrate inhibit?

A
  • PFK1 (glycolysis)

- ACC (FA synthesis)

28
Q

Which components of the TCA cycle have 3 carboxyl groups?

A
  • Isocitrate

- Citrate

29
Q

Which enzyme catalyzes the hydration/dehydration step of the TCA cycle? What does it form? From what?

A
  • Enzyme: Aconitase

- Citrate -> Isocitrate

30
Q

Which enzyme catalyzes the oxidative decarboxylation step of the TCA cycle? What does it form? From what?

A
  • Enzyme: Isocitrate dehydrogenase

- Isocitrate -> a-ketoglutarate

31
Q

What does isocitrate dehydrogenase synthesize as a by-product?

A

NADH or NAPDH depending on the enzyme isoform

32
Q

Which steps generate energy molecules in the TCA cycle?

A
  • Isocitrate dehydrogenase (NADH)
  • a-Ketoglutarate dehydrogenase complex (NADH)
  • Succinyl-CoA Synthetase (GTP or ATP)
  • Succinate dehydrogenase (FADH2)
  • Malate dehydrogenase (NADH)
33
Q

Which steps generate CO2 in the TCA cycle?

A
  • Isocitrate dehydrogenase

- a-Ketoglutarate dehydrogenase complex

34
Q

Which enzyme catalyzes the second oxidative decarboxylation step of the TCA cycle? What does it form? From what?

A
  • Enzyme: a-ketoglutarate dehydrogenase complex

- a-Ketoglutarate –> Succinyl-CoA

35
Q

Which enzyme of the TCA cycle is similar to the PDC?

A

a-Ketoglutarate dehydrogenase complex

36
Q

Which enzyme catalyzes the substrate-level phosphorylation step of the TCA cycle? What does it form? From what?

A
  • Enzyme: Succinyl-CoA Synthetase

- Succinyl-CoA –> Succinate

37
Q

Differentiate the two isoforms of Succinyl-CoA synthetase.

A

o Isoform that has affinity for GDP synthesizes GTP

o Isoform that has affinity for ADP synthesizes ATP

38
Q

Which enzyme can convert a GTP into an ATP (or vice-versa)?

A

Nucleoside diphosphate kinase

39
Q

Differentiate synthetase and synthase.

A

o Synthetase: when synthesis involves an energy molecule

o Synthase: when synthesis does not involve energy

40
Q

Differentiate kinase and phosphorylase.

A

o Kinase: when synthesis involves an energy molecule

o Phosphorylase: when synthesis does not involve energy

41
Q

Which enzyme catalyzes the dehydrogenation step of the TCA cycle? What does it form? From what?

A
  • Enzyme: Succinate dehydrogenase

- Succinate –> Fumarate

42
Q

Which enzyme of the TCA cycle is the only one that is located on the inner wall of the mitochondria?

A

Succinate dehydrogenase

43
Q

Which enzyme catalyzes the second hydration step of the TCA cycle? What does it form? From what?

A
  • Enzyme: Fumarase

- Fumarate –> Malate (OH- is added, then H+ is added)

44
Q

Which enzyme catalyzes the second dehydrogenation step of the TCA cycle? What does it form? From what?

A
  • Enzyme: Malate dehydrogenase

- Malate –> Oxaloacetate

45
Q

What are the products of the TCA cycle?

A

Acetyl-CoA = 2CO2 + 3 NADH + 1 FADH2 + 1 ATP/GTP

46
Q

What is an amphibolic pathway? Give an example.

A
  • Biochemical pathway that involves catabolism and anabolism
    (hub of mechanisms)
  • TCA cycle
47
Q

What is the PDC inhibited by?

A

Inhibited by ATP, Acetyl-CoA, NADH, fatty acids

48
Q

What is the PDC activated by?

A

Activated by AMP, CoA, NAD+, Ca2+

49
Q

What is citrate synthase inhibited by?

A

Inhibited by NADH, Succinyl-CoA, citrate, ATP

50
Q

What is citrate synthase activated by?

A

Activated by ADP

51
Q

What is isocitrate dehydrogenase inhibited by?

A

Inhibited by ATP

52
Q

What is isocitrate dehydrogenase activated by?

A

Activated by Ca2+, ADP

53
Q

What is the a-ketoglutarate dehydrogenase complex inhibited by?

A

Inhibited by Succinyl-CoA, NADH

54
Q

What is the a-ketoglutarate dehydrogenase complex activated by?

A

Activated by Ca2+

55
Q

Which steps are irreversible in the TCA cycle?

A

1, 3, 4

2) Biochemistry II (23 decks)

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