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1) Biochemistry I > TCA Cycle > Flashcards

TCA Cycle Flashcards

1
Q

The 2 pyruvate molecules produced in the cytosol in the glycolytic process retain 90% of the energy stored in glucose. How is this energy recovered? Where do these processes take place.

A
  • by the TCA cycle and oxidative phosphorylation

- take place inside the mitochondrial of eukaryotic cells

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2
Q

Explain the structure of the mitochondrial membranes.

A
  • mitochondria enclosed by two membranes – inner and outer separated by an inter membrane space
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3
Q

What does the inner membrane possess in terms of structure?

A

Inward folds called cristae

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4
Q

What is another word for inner mitochondria space?

A

Matrix

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5
Q

Define TCA.

A

Tricarboxylic Acid Cycle

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6
Q

How is mitochondria inherited?

A

Materanally

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7
Q

How is the permeability of the outer membrane?

A

has large permeable channels or porins that allow compounds <5, 000 Da to pass freely

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8
Q

How is the permeability of the inner membrane?

A
  • Highly impermeable

- Contains transport proteins (carriers) that transport specific substrates

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9
Q

What does the inner membrane contain?

A

succinate dehydrogenase complex NADH dehydrogenase complex electron transport chain components ATPase

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10
Q

What does the matrix contain?

A

soluble enzymes of TCA cycle

Pyruvate dehydrogenase complex DNA & ribosomes

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11
Q

What does the intermembrane space contain?

A

Enzymes

- Ex: adenylate kinase (ATP + AMP -> 2ADP)

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12
Q

Where is ATP produced during TCA and oxidative phosphorylation? Where is it exporter? How?

A
  • Produced in mitochondrial matrix

- Exported to the cytosolic space by exchangers (membrane transporters)

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13
Q

What are porins?

A

Channels that allow small compounds to pass through (ex: NADH and ATPase)

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14
Q

What is the inner membrane impermeable to? What does it less pass?

A
  • Impermeable to charged compounds

- Lets small compounds like O2 pass through

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15
Q

How does pyruvate go through into the matrix?

A

Pyruvate is charged, will diffuse into intermembrane space, transporter carrier will transport it to the matrix (pyruvate translocase)

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16
Q

What are 2 other names for the TCA cycle?

A

Citric acid cycle or Krebs cycle

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17
Q

What goes into the TCA cycle?

A

Pyruvate in the mitochondria

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18
Q

What happens to pyruvate when it enters the mitochondria?

A
  • Is decarboxylated and coupled to Coenzyme A (Co-A)

- Produces NADH

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19
Q

What is the conversion of pyruvate to acetyl-CoA catalyzed by? Is the delta G^o’ favourable?

A
  • Pyruvate dehydrogenase complex

- Yes

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20
Q

Where is pyruvate dehydrogenase complex located?

A

In the inner membrane of mitochondria

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21
Q

What is the overall equation for the oxidative decarboxylation of pyruvate to form acetyl-CoA

A

pyruvate + NAD+ + CoASH → acetyl-CoA + CO2 + NADH + H+

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22
Q

What is pyruvate dehydrogenase formed of?

A
  • Multi-subunit with 3 activities

- E1, E2, E3

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23
Q

What is the activity of E1, E2, E3?

A

E1: pyruvate decarboxylation
E2: acetyl CoASH transfer
E3: re-oxidize dihydrolipoamide

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24
Q

What are the coenzymes for E1, E2, E3?

A

E1: TPP
E2: lipoic acid and CoASH
E3: NAD+ FAD

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25
Q

What is the overall TCA reaction?

A

Acetyl-CoA + 3NAD+ + FAD + GDP + Pi +2H2O → 2CO2 + 3NADH + FADH2 + Co-ASH + GTP + 2H+

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26
Q

How many CO2 molecules does 1 glucose molecule make?

A

1 Glucose = 6 CO2

27
Q

Explain the structure of the pyruvate dehydrogenase complex.

A

Outer: E1
Middle: E2
Centre: E3

28
Q

Why is the pyruvate dehydrogenase complex efficient? What can this structure be called?

A
  • Substrate never released from enzyme complex, passes substrate on the the next step directly
  • Substrate channel
29
Q

Name the 3 coenzymes in the TCA cycle

A
  • Thiamine pyrophosphate (TPP)
  • Lipoic acid
  • Coenzyme A
30
Q

What does TPP do?

A
  • Thiazolium ring has a very acidic H
  • Will leave a - charge on the carbon -> generates carbanion
  • Which attracts pyruvate for decarboxylation
31
Q

What does lipoic acid do?

A

Disulfide bond is easily interconverted between SH and SS

- Adds or removes 2e- and 2p+

32
Q

What does coenzyme A do?

A

forms high energy thioesther because of the SH

33
Q

NADH and FADH2 are both high energy electron carriers. What do they carry?

A

NADH: 2e- and 2p+
FADH2: 2e- and 2p+

34
Q

What goes in/comes out of the mechanism for pyruvate dehydrogenase?

A

In: pyruvate, acetyl CoA, NAD+
Out: CO2, NADH, acetyl CoA

35
Q

What does TPP do in the mechanism for pyruvate dehydrogenase?

A

TPP attacks pyruvate and forms a covalent C-C bond, which breaks another C-bond and releases a molecule of CO2

36
Q

What does HETPP do in the mechanism for pyruvate dehydrogenase?

A
  • Covalent intermediate (needs to be taken off)

- Nucleophile attaks lipoic acid, forms intermediate with a covalent esther bond

37
Q

Why does arsenic kill?

A

Because it reacts with hydrolipoic acid, can’t regenerate lipoic acid, no more TCA cycle

38
Q

What intermediates can be pulled out of the TCA cycle to make other compounds?

A

Protein and glucose

39
Q

TCA cycle is not just for energy production. What does it also do?

A

A reservoir for making precursors

40
Q

What is the anaplerotic reaction? What is it catalyzed by?

A
  • Mechanism that keeps supplies of oxaloacetate very high

- Catalyzed by pyruvate carboxylase

41
Q

Name the 3 enzymes that regulate the TCA cycle.

A

1) Citrate synthase
2) Isocitrate dehydrogenase
3) a ketoglutarate dehydrogenase

42
Q

What reaction is citrate synthase responsible for?

A

Oxaloacetate + acetyl -> citrate

43
Q

What is citrate synthase inhibited by?

A

succinyl-CoA, citrate , ATP and NADH

44
Q

What ratios are high in resting cells?

A

NADH/NAD+ and ATP/ADP

45
Q

What reaction is isocitrate dehydrogenase responsible for?

A

citrate↔isocitrate → α−ketoglutarate

46
Q

What is isocitrate dehydrogenase inhibited by?

A

inhibited by high levels of ATP & NADH

47
Q

What is isocitrate dehydrogenase activated by?

A

activated by high level of ADP and NAD+

48
Q

What reaction is a-ketoglutarate dehydrogenase responsible for?

A

α ketoglutarate → succinyl-CoA

49
Q

What is a-ketoglutarate inhibited by?

A

high levels of NADH & succinyl-CoA

50
Q

What is a-ketoglutarate activated by?

A

activated by high level of AMP

51
Q

How many molecules of ATP does one pyruvate generate? One molecule of glucose?

A

12.5 ATP per pyruvate

25 ATP per glucose

52
Q

What is produced in the TCA cycle?

A

4 NADH, 1 FADH2, 1 GTP

53
Q

How many molecules of ATP does glycolysis generate?

A
  • 2 ATP + 2 NADH (2.5 ATP per NADH) -> 7 molecules of ATP
54
Q

What is the net yield of ATP for one glucose molecule from glycolysis through oxidative phosphorylation?

A

30-32 ATP

55
Q

Where is the pyruvate dehydrogenase complex located?

A

Matrix

56
Q

Where is the NADH dehydrogenase complex located?

A

Inner membrane

57
Q

Where are DNA and ribosomes located?

A

matrix

58
Q

Where is succinate dehydrogenase complex located?

A

Inner membrane

59
Q

Where are the electron transport chain components located?

A

Inner membrane

60
Q

Where is ATPase located?

A

Inner membrane

61
Q

Which steps in the TCA cycle are not favourable?

A 
Cis-Aconitase (13.3 kJ/mol)
Malate dehydrogenase (29.7 kJ/mol)
62
Q

Which step in the TCA cycle is at equilibrium (0 kJ/mol)?

A

Succinate dehydrogenase

63
Q

What are three properties of O2 that favour energy extraction?

A
  • O2 abundant (21% of air)
  • O2 diffuses through membranes
  • O2 very reactive and easily accepts electrons

1) Biochemistry I (12 decks)

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