Week 6: Citric Acid Cycle Flashcards

1
Q

Is the CAC aerobic or anaerobic?

A

Aerobic

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2
Q

Where is the citric acid cycle located?

A

Mitochondria in muscle and liver cells

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3
Q

Where are the enzymes for the CAC located?

A

Mitochondrial matrix

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4
Q

How does the RBC the receive energy if they don’t have mitochondria?

A

RBCs rely on energy generated from glycolysis

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5
Q

What are the 2 coenzymes for CAC?

A

NADH and FADH2

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6
Q

What would the CAC link?

A

The chemical energy of nutrients and chemical energy of ATP

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7
Q

Why would CAC be considered an aerobic metabolic process?

A

It links the ETC and oxidative phosphorylation

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8
Q

Which enzyme located in the inner membrane of the mitochondria and not the matrix?

A

Succinate dehydrogenase

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9
Q

How does pyruvate enter the mitochandria?

A

Must be transported from the cytosol into the matrix through transporter in the inner membrane

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10
Q

Where would would oxidative phosphorylation occur in?

A

Mitochondrial inner membrane

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11
Q

What needs to happen for glycolysis to transition to CAC?

A
  1. Conversion of pyruvate into Acetyl-CoA

2. Acetyl-CoA is enters the CAC

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12
Q

What occurs during the conversion of pyruvate to acetyl-CoA?

A

The oxidative decarboxylation of pyruvate by pyruvate dehydrogenase complex into Acetyl-CoA

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13
Q

Is pyruvate to Acetyl-CoA reversible or irreversible?

A

Irreversible

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14
Q

What are the 5 coenzymes involved with the conversion of pyruvate to Acetyl-CoA?

A
  1. TPP
  2. Lipoyllysine
  3. FAD
  4. NAD+
  5. CoA-SH
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15
Q

What are the 3 enzymes in the pyruvate dehydrogenase complex?

A
  1. Pyruvate dehydrogenase (E1)
  2. Dihydrolipoyl transacetylase (E2)
  3. Dihydrolipoyl dehydrogenase (E3)
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16
Q

What are the advantages of a multi-enzyme complex?

A
  1. Shorter distance between catalytic sites channeling of substrates from one catalytic site to another
  2. Channeling minimizes side reactions
  3. The regulation of activity of one subunit affects the entire complex
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17
Q

What enzymes of the CAC cause substrate-level phosphorylation?

A

Succinyl-CoA synthetase

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18
Q

What occurs in Step 1 of CAC?

A

Acetyl-CoA and oxaloacetate is condensated by citrate synthase to make citrate and CoA-SH

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19
Q

Why is Step 1 of CAC considered favorable and irreversible?

A
  1. Regulated by substrate availability and product inhibition
  2. Inhibited by increased concentration of ATP, NADH, citrate, and succinyl-CoA
  3. Stimulated by ADP
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20
Q

What occurs during Step 2 of CAC?

A
  1. H2O is eliminated from citrate by aconitase to for cis-Aconitate
  2. H2O is added to cis-Aconitate by aconitase to form isocitrate
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21
Q

Why does Step 2 of CAC require 2 steps?

A

Citrate is a poor substrate for oxidation, isocitrate is good for oxidation

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22
Q

Why is Step 2 of CAC unfavorable/reversible?

A

Product concentration kept low to pull forward

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23
Q

What occurs during Step 3 of CAC?

A
  1. Isocitrate is oxidized to oxalosuccinate by NAD+ and Isocitrate Dehydrogenase
  2. Oxalosuccinate is decarboxylated by Isocitrate Dehydrogenase to a-Ketoglutarate releasing CO2
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24
Q

Why is Step 3 of CAC considered favorable/irreversible?

A
  1. If ATP and NADH is high, enzyme is inhibited (high energy signal)
  2. Stimulated by increased ADP and Ca2+ (low energy signal)
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25
Q

What occurs during Step 4 of CAC?

A

a-ketoglutarate is oxidized and decarboxilated by a-ketoglutarate dehydrogenase complex to succinyl-CoA, NADH, and CO2

26
Q

What kind of bond is Succinyl-CoA?

A

High energy thioester bond

27
Q

Why is Step 4 of CAC favorable/irreversible?

A
  1. Succinyl-CoA or NADH increase inhibits enzyme

2. Enzyme is stimulated by icnreased Ca+

28
Q

What occurs during Step 5 of CAC?

A

Thioester energy bond from Succinyl-CoA is broken by GDP, Pi, and succinyl-CoA synthetase to produce Succinate

29
Q

Why is Step 5 of CAC considered favorable/reversible?

A

Product concentration kept low to pull forward

30
Q

What occurs during Step 6 of CAC?

A

Succinate is oxidated by FAD and succinate dehydrogenase to fumarate

31
Q

Why is FAD used instead of NAD in Step 6 of CAC?

A

Reduction potential of C-H bond is too low for production of NADH

32
Q

Why is succinate dehydrogenase bound to the mitochondrial inner membrane?

A

It also serves as Complex II in the ETC

33
Q

What is the delta G of Step 6 of CAC?

A

0

34
Q

What occurs during Step 7 of CAC?

A

Fumarate is converted to L-Malate by fumerase and addition of H2O

35
Q

Why is Step 7 of CAC favorable/reversible?

A

Product concentration kept low to pull reaction forward

36
Q

What occurs during Step 8 of CAC?

A

L-Malate is oxidized by L-malate dehydrogenase and NAD+ to form oxaloacetate

36
Q

What occurs during Step 8 of CAC?

A

L-Malate is oxidized by L-malate dehydrogenase and NAD+ to form oxaloacetate

37
Q

Why is Step 8 of CAC unfavorable/reversible?

A

Oxaloacetate concentration kept very low by citrate synthase pulling the reaction forward

38
Q

What is the overall reaction of the pyruvate dehydrogenase complex?

A

Pyruvate + CoA-SH + NAD+ → Acetyl-CoA + NADH + CO2 +H+

39
Q

What is the overall reaction of the CAC?

A

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

40
Q

What is the overall reaction of pyruvate oxidation?

A

Pyruvate + 4NAD+ + FAD + GDP + Pi + 2H2O → 3CO2 + 4NADH + FADH2 + GTP + 4H+

41
Q

How much is ATP is produced from CAC?

A

12.5 ATP/pyruvate

25 ATP/glucose

42
Q

Why does NADH have a greater reduction potential of FADH2?

A

E is more negative

43
Q

What does it mean when E is more negative?

A

The greater the energy available for ATP generation when that compound passes it electron to oxygen

44
Q

How does oxaloacetate leave the mitochondria?

A

Reduced to malate which exits the mitochondria into cytosol

45
Q

How is NADH produced in the cytosol?

A

Malate is oxidized to oxaloacetate by malate dehydrogenase

46
Q

What does it mean to be amphibiolic?

A

Reactions that are both catabolic and anabolic

47
Q

What happens to the CAC when energy levels are high?

A

The CAC is cycled is slowed and the intermediates are diverted to other purposes

48
Q

What reactions are used to replenish other biomolecules?

A

Anaplerotic reactions

49
Q

What enzymes of the CAC are highly favorable and irreversible steps?

A
  1. Pyruvate dehydrogenase complex
  2. Citrate synthase
  3. Isocitrate dehydrogenase
  4. Ketogluterate dehydrogenase complex
50
Q

What are the general regulatory mechanism?

A
  1. Activated by substrate availability

2. Inhibited by product accumulation

51
Q

What are the inhibitors of the CAC?

A

NADH and ATP

52
Q

What are the activators of CAC?

A

NAD+, Ca2+, AMP, ADP

53
Q

Which actives and inactivates Pyruvate Dehydrogenase?

A

Activate: Dephosphorylation

Inactivate: Phosphorylation

54
Q

Which PDHs are part of the mammalian complex?

A

Kinase and phosphorylase

55
Q

What happens to kinase when ATP levels are high?

A

PDH is phosphorylated and less Acetyl-CoA is produced

56
Q

What happens to kinase when ATP levels are low?

A

Kinase is less active and phosphorylase removes phosphate from PDH and more acetyl-CoA is produced

57
Q

What is a strong activator of the phosphatase?

A

Ca2+

58
Q

How is citrate synthase inhibited by succinyl-CoA?

A
  1. α-Ketoglutarate is an important branch point for amino acid metabolism.
  2. Succinyl-CoA communicates flow at this branch point to the start of the cycle.
59
Q

How does regulation of isocitrate dehydrogenase control citrate levels?

A
  1. Aconitase is reversible.
  2. Inhibition of isocitrate dehydrogenase leads to accumulation of isocitrate and reverses acconitase.
  3. Accumulated citrate leaves mitochondria and inhibits phosphofructokinase (PFK) in glycolysis.