Biochemistry: Citric Acid Cycle

Front 1

Where is pyruvate oxidatively decarboxylated to form acetyl CoA?

Back 1

In the mitochondrial matrix!

Front 2

What forms acetyl CoA from pyruvate?

Back 2

Pyruvate dehydrogenase complex

Front 3

Substrates are completely oxidized to form what?

Back 3

CO2

Front 4

Electrons are removed from substrates and transferred to what?

Back 4

Carriers like NADH and FADH2

Front 5

What do NADH and FADH2 do?

Back 5

They deliver electrons to the respiratory chain and eventually to O2

Front 6

When O2 is NOT present, pyruvate is converted into what?

Back 6

Lactic acid or ethanol

Front 7

When O2 IS present, pyruvate is converted into what?

Back 7

acetyl CoA

Front 8

What is the link between glycolysis and the citric acid cycle?

Back 8

The IRREVERSIBLE conversion of pyruvate into acetyl CoA

Front 9

What is the pyruvate dehydrogenase complex?

Back 9

Large complex of 3 distinct enzymes, each with its own active site.

Front 10

What are the 3 enzymes that make up the pyruvate dehydrogenase complex?

Back 10

1. Pyruvate dehydrogenase component, E1

2. Dihydrolipoyl transacetylase, E2

3. Dihydrolipoyl dehydrogenase, E3

Front 11

FAD can pick up what?

Back 11

2 electrons and 2 protons to form FADH2

Front 12

What 3 enzymes serve as catalytic coenzymes of the pyruvate dehydrogenase complex?

Back 12

1. Thiamine pyrophosphate (TPP)

2. Lipoic acid

3. Flavin adenine dinucleotide (FAD)

Front 13

What 2 enzymes serve as stoichiometric coenzymes of the pyruvate dehydrogenase complex?

Back 13

1. CoA

2. NAD+

Front 14

What do stoichiometric coenzymes do?

Back 14

They function as substrates

Front 15

What reaction does pyruvate dehydrogenase component catalyze?

Back 15

Oxidative decarboxylation of pyruvate

Front 16

What reaction does dihydrolipoyl transacetylase catalyze?

Back 16

Transfer of acetyl group to CoA

Front 17

What reaction does dihydrolipoyl dehydrogenase catalyze?

Back 17

Regeneration of the oxidized form of lipoamide

Front 18

In basic terms, what are the three steps to converting pyruvate into acetyl CoA?

Back 18

1. Decarboxylation

2. Oxidation

3. Transfer to CoA

Front 19

What happens in the inner membrane of mitochondria?

Back 19

Respiratory chain and ATP synthesis

Front 20

What is the net reaction for pyruvate dehydrogenase?

Back 20

Pyruvate + CoA + NAD+

--->

Acetyl CoA + CO2 + NADH + H+

Front 21

What is the prosthetic group for pyruvate dehydrogenase component?

Back 21

TPP

Front 22

What is the prosthetic group for dihydrolipoyl transacetylase?

Back 22

Lipoamide

Front 23

What is the prosthetic group for dihydrolipoyl dehydrogenase?

Back 23

FAD

Front 24

Back 24

FAD

Front 25

Back 25

TPP

Front 26

Back 26

Lipoic acid

Front 27

Why is TPP good at attacing R2CO groups?

Back 27

TPP forms a stable carbanion

Front 28

How is pyruvate decarboxylated? What is formed?

Back 28

Carbanion of TPP + Pyruvate + 2H+ with pyruvate dehydrogenase component (E1)

forms

hydroxyethyl-TPP and CO2

Front 29

Back 29

Carbanion of TPP

Front 30

Back 30

Hydroxyethyl-TPP

Front 31

What is done to the hydroxyethyl-TPP?

Back 31

Via pyruvate dehydrogenase component (E1), H-TPP is oxidized while being simultaneously transferred to lipoamide (a derivative of lipoic acid) to form acetyllipoamide.

Front 32

Back 32

Acetyllipoamide

Front 33

CoA + Acetyllipoamide forms what?

Back 33

Acetyl CoA and dihydrolipoamide via dihydrolipoyl transacetylase (E2)

Front 34

Back 34

Dihydrolipoamide

Front 35

Pyruvate dehydrogenase complex cannot complete another catalytic cycle until what is done?

Back 35

Until dihydrolipoamide is oxidized to lipoamide via dihydrolipoyl dehydrogenase (E3)

Front 36

Back 36

Lipoamide

Front 37

When the pyruvate dehydrogenase complex is reset, what is done electron wise?

Back 37

2 electrons are transferred to an FAD prosthetic group and then to NAD+ (so FAD and NADH remain)

Front 38

What does TPP do with its electrons in regards to pyruvate?

Back 38

TPP shares its electrons with pyruvate.

Front 39

Lipoamide has what side chain?

Back 39

Lysine side chain

Front 40

What is the role of lipoate (lipoic acid)?

Back 40

It serves as a place for the acetyl group from TPP which results in the formation of an energy-rich thioester bond.

Front 41

What is the role of FAD for pyruvate dehydrogenase complex?

Back 41

It takes electrons from dihydrolipoamide so lipoamide can be formed again.

Front 42

Back 42

FADH2

Front 43

FAD picks up 2 electrons and 2 protons from dihydrolipoamide to form what?

Back 43

FADH2

Front 44

Back 44

Pyruvate is decarboxylated to form hydroxyethyl-TPP via E1

Front 45

Back 45

Lipoamide arm of E2 movies into the active site of E1

Front 46

Back 46

E1 catalyzes the transfer of the acetyl group to the lipoamide

Front 47

Back 47

E2 catalyzes the transfer of the acetyl moiety to CoA to form acetyl CoA

Front 48

Back 48

The oxidation of the dihydrolipoamide by FAD

Front 49

Back 49

The final product, NADH, is produced with the reoxidation of FADH2 to FAD.

Front 50

TRUE OR FALSE: Pyruvate dehydrogenase reaction is reversible in animals. What does this mean?

Back 50

FALSE. It is irreversible. It means you can't make glucose from fats.

Front 51

What is the key means of regulating the pyruvate dehydrogenase complex?

Back 51

Phosphorylation!

Front 52

What does Pyruvate Dehydrogenase (PDH) kinase do? What does it need?

Back 52

It phosphorylates PDH and INACTIVATES it.

It needs ATP to do this!

Front 53

Deactivation of Pyruvate Dehydrogenase is reversed by what?

Back 53

By PDH phosphatase which REMOVES the phosphoryl group through hydrolysis and ACTIVATES PDH

Front 54

High NADH/NAD+, acetyl CoA/CoA, and ATP/ADP ratios stimulate what?

Back 54

Stimulate pyruvate dehydrogenase kinase which phosphorylates PDH and INACTIVATES it

Front 55

Low NADH/NAD+, acetyl CoA/CoA, and ATP/ADP ratios stimulate what?

Back 55

Stimulate the INHIBITION of PDH kinase (so PDH won't get phosphorylated)

Front 56

What does a rise in Ca2+ concentration do?

Back 56

It activates PDH phosphatase which removes phosphoryl groups on PDH and ACTIVATES it.

Front 57

What is the function of the citric acid cycle?

Back 57

Harvesting of high-energy electrons from carbon fuels in the form of NADH and FADH2

Front 58

What are the two parts of the citric acid cycle?

Back 58

One oxidizes carbon atoms to CO2

Other regenerates oxaloacetate

Front 59

What drives ATP synthesis?

Back 59

Electron-transport chain

Front 60

Oxaloacetate and Acetyl CoA combine to form what? What catalyzes the reaction?

Back 60

Combine to form Citryl CoA via citrate synthase

Front 61

Back 61

Citryl CoA

Front 62

Citryl CoA is converted into Citrate via what? What powers it?

Back 62

Hydrolysis of the high-energy thioester bond powers the synthesis of Citrate

Front 63

What is this and how is it formed?

Back 63

cis-aconitate is the intermediate between Citrate and Isocitrate.

It is formed via aconitase.

Front 64

Why is Citrate isomerized to Isocitrate?

Back 64

Citrate's hydroxyl group is not properly located for oxidative decarboxylations to occur

Front 65

How is Isocitrate converted into alpha-ketoglutarate?

Back 65

Oxidative decarboxylation of isocitrate to form oxalosuccinate which then converts to alpha-ketoglutarate via isocitrate dehydrogenase.

Front 66

Isocitrate to oxalosuccinate forms what?

Back 66

NADH

Front 67

Back 67

Oxalosuccinate

Front 68

How is alpha-ketoglutarate converted into Succinyl CoA?

Back 68

Oxidative decarboxylation via alpha-ketoglutarate dehydrogenase complex

Front 69

By the time Succinyl CoA is made, what have been released?

Back 69

2 CO2 molecules

2 NADH molecules

Front 70

The cleavage of the thioester bond of Succinyl CoA is coupled with what?

Back 70

The phosphorylation of a purine nucleoside diphosphate, usually ADP

Front 71

How is Succinyl CoA converted to Succinate?

Back 71

Succinyl CoA Synthase catalyzes Succinyl CoA + Pi + ADP to form Succinate + CoA + ATP

Front 72

What is the only step in the Citric Acid cycle that directly yield a compound with high phosphoryl-transfer potential?

Back 72

Succinyl CoA to Succinate via Succinyl CoA Synthase

Front 73

How is Succinate converted to Fumarate? What is produced?

Back 73

Oxidation with FAD and Succinate Dehydrogenase produces Fumarate and FADH2

Front 74

How is Fumarate converted to Malate?

Back 74

Fumarate is hydrated to L-malate via Fumarase

Front 75

How is Malate converted to Oxaloacetate? What does this produce?

Back 75

Malate is oxidized with NAD+ to form oxaloacetate via malate dehydrogenase forming NADH

Front 76

What are the 4 oxidation reactions of the Citric Acid Cycle?

Back 76

1. Isocitrate to a-ketoglutarate

2. a-Ketoglutarate to Succinyl CoA

3. Succinate to Fumarate

4. Malate to Oxaloacetate

Front 77

In what 3 steps is NADH made?

Back 77

1. Isocitrate to a-ketoglutarate

2. a-ketoglutarate to Succinyl CoA

3. Malate to Oxaloacetate

Front 78

Although citrate is symmetric, the carboxyl groups at the ends are what?

Back 78

NOT equivalent meaning that citrate can only bind one way in the aconitase active cite

Front 79

Which step of the Citric Acid Cycle produces ATP?

Back 79

Succynl CoA to Succinate

Front 80

What are the primary control points of the Citric Acid Cycle?

Back 80

Regulating the allosteric enzymes isocitrate dehydrogenase and a-ketoglutarate dehydrogenase

Front 81

What stimulates isocitrate dehydrogenase?

Back 81

ADP because it signifies the need for more energy

Front 82

What two things inhibit isocitrate dehydrogenase?

Back 82

ATP and NADH because it signifies that energy is already present

Front 83

What 3 things inhibit a-ketoglutarate dehydrogenase?

Back 83

1. ATP

2. Succinyl CoA

3. NADH

Front 84

The inhibition of isocitrate dehydrogenase causes what? What does this lead to?

Back 84

The buildup of citrate which signals phosphofructokinase to halt glycolysis

Front 85

What are the 3 fates of Oxaloacetate?

Back 85

1. Glucose

2. Continuation in the citric acid cycle

3. Aspartate and then amino acids, purines, pyrimidines

Front 86

What are the 2 fates of Citrate?

Back 86

1. Fatty acids, sterols

2. Continuation in the citric acid cycle

Front 87

What are the two fates of a-ketoglutarate?

Back 87

1. Glutamate and then other amino acids and purines

2. Continuation in the citric acid cycle

Front 88

What are the two fates of Succinyl CoA?

Back 88

1. Porphyrins, heme, chlorophyll

2. Continuation in the citric acid cycle

Front 89

How is oxaloacetate replenished?

Back 89

Pyruvate is converted into oxaloacetate via pyruvate carboxylase

Front 90

What is the Glyoxylate Cycle?

Back 90

Cycle that bypasses the two decarboxylation steps of the citric acid cycle to convert acetyl CoA into glucose. ONLY IN PLANTS