Citric Acid Cycle

Question 1

The CAC is a circular pathway of ____ reactions that oxidize acetyl-CoA to carbon dioxide.

Answer 1

8

Question 2

Where does the CAC take place?

Answer 2

The mitochondrial matrix

Question 3

What are the 8 intermediates of the CAC (excluding acetyl-CoA)?

Answer 3

1. Citrate
2. Isocitrate
3. Alpha-ketoglutarate
4. Succinyl-CoA
5. Succinate
6. Fumarate
7. Malate
8. Oxaloacetate

Question 4

What are the 8 enzymes of the CAC?

Answer 4

1. Citrate synthetase
2. Aconitase
3. Isocitrate dehydrogenase
4. Alpha-ketoglutarate dehydrogenase
5. Succinyl-CoA synthetase
6. Succinate dehydrogenase
7. Fumarase
8. Malate dehydrogenase

Question 5

What is the structure of acetyl CoA?

Answer 5

Question 6

What is the structure of pyruvate?

Answer 6

Question 7

What is the structure of oxaloacetate?

Answer 7

Question 8

Citrate synthase converts ________________ and __________________ to citrate via a Claisen condensation.

Answer 8

Acetyl-CoA

Oxaloacetate

Question 9

Citrate synthase produces citrate and expels ______________.

Answer 9

CoASH

Question 10

What is the mechanism of citrate synthase?

Answer 10

An irreversible Claisen condensation

Question 11

What is the mechanism of action of citrate sythase?

Answer 11

1. Acidic proton deprotonates and carbanion forms on acetyl-CoA
2. Carbanion attacks C carbonyl and O protonates
3. Water attacks chiral C and expels CoASH
4. Citrate forms

Question 12

Aconitase converts cistrate to isocitrate via an ___________________ and dehydration.

Answer 12

Isomerization

Question 13

What is the structure of isocitrate?

Answer 13

Question 14

The enzyme aconitase catalyzes the reversible transformation of citrate to isocitrate through the intermediary formation of the tricarboxylic acid ______________________, which normally does not dissociate from the active site.

Answer 14

Cis-aconitase

Question 15

Aconitase contains an _________________________, which acts both in the binding of the substrate in the active site and in the catalytic addition and removal of water.

Answer 15

Iron-sulfur center

Question 16

What is the mechanism of action for aconitase?

Answer 16

1. Proton abstraction
2. Formation of alkene
3. Expulsion of hydroxyl
4. Formation of cis-aconitase
5. Water is added across alkene
6. Formation of isocitrate

Question 17

The iron-sulfur cluster of aconitase assists in what part of the enzyme’s mechanism?

Answer 17

The removal of water

Question 18

The iron-sulfur cluster of aconitase contains a __________ residue that coordinates four iron artoms and four sulfur atoms.

Answer 18

Cysteine

Question 19

Citrate synthase incorporates acetyl-CoA only into the pro-__ carboxymethyl group and that aconitase abstracts a proton only from the pro-__ carboxymethyl group of citrate.

Answer 19

pro-S

pro-R

Question 20

Isocitrate dehydrogenase catalyzes the formation of alpha-ketoglutarate from isocitrate via an ________________ _________________.

Answer 20

Oxidative decarboxylation

Question 21

Isocitrate dehydrogenase catalyzes an oxidative decarboxylation of a beta-keto acid just as ____________________ _________________ in the pentose phosphate pathway.

Answer 21

6-phosphogluconate dehydrogenase

Question 22

What is the structure of alpha-ketoglutarate?

Answer 22

Question 23

What is the mechanism of action for isocitrate dehydrogenase?

Answer 23

1. Isocitrate binds enzyme and is oxidized via hydride transfer to NAD+ or NADP+
2. Interaction of the carbonyl O with a bound Mg2+ or Mn2+ increases electron-withdrawing capacity of carbonyl group and facilitates decarboxylation
3. Rearrangement of enol intermediate generates alpha-ketoglutarate

Question 24

What is the structure of succinyl-CoA?

Answer 24

Question 25

alpha-ketoglutarate dehydrogenase catalyzes the oxidative decarboxylation of an \_\_\_\_-keto acid.

Answer 25

Alpha keto acid

Question 26

Alpha-ketoglutarate dehydrogenase cataylzes the conversion of __________________________ to \_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_.

Answer 26

Alpha-ketoglutarate Succinyl-CoA

Question 27

What is the mechanism of action for alpha-ketoglutarate dehydrogenase?

Answer 27

1. TPP carbanion attacks alpha keto group 2. Gamma O kicks back, expels carbon dioxide, and forms carbanionic intermediate 3.

Question 28

Citrate synthase incorporates acetyl-coenzyme A only into the pro-\_\_\_ carboxymethyl group and aconitase abstracts a protron from only the pro-\_\_\_ carboxymethyl group of citrate.

Answer 28

Pro-S Pro-R

Question 29

What coenzymes are required for alpha-ketoglutarate dehydrogenase to function?

Answer 29

TPP Lipoic acid CoASH FAD NAD+

Question 30

\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_ refers to an enzyme that catalyzes a condensation reaction that involves a nucleotide triphosphate while _______________ refers to an enzyme that catalyzes a condensation reaction that does not involve a nucleotide triphosphate.

Answer 30

Synthetase Synthase

Question 31

What cosubstrate is required for the reaction catalyzed by succinyl-CoA synthetase?

Answer 31

Inorganic phosphate

Question 32

What amino acid residue assists in the succinyl-CoA synthetase reaction?

Answer 32

A deprotonated histidine

Question 33

What is the function of GDP in the succinyl-CoA synthetase mechanism?

Answer 33

To dephosphorylate the amino acid residue and to form GTP

Question 34

Succinyl-CoA synthetase catalyzes the conversion of _______________ to \_\_\_\_\_\_\_\_\_\_\_\_\_\_.

Answer 34

Succinyl-CoA to succinate

Question 35

Which enzyme in the CAC reduces FAD?

Answer 35

Succinate dehydrogenase

Question 36

\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_ _______________ catalyzes the conversion of succinate to fumarate.

Answer 36

Succinate dehydrogenase

Question 37

Which enzyme in the CAC catalyzes a hydration reaction?

Answer 37

Fumarase

Question 38

\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_ catalyzes the conversion of fumarate to malate via a hydration reaction.

Answer 38

Fumarase

Question 39

Isocitrate dehydrogenase, alpha-ketoglutarate dehydrogenase, and ___________________ dehydrogenase reduce NAD+ to NADH in the CAC.

Answer 39

Malate dehydrogenase

Question 40

\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_ _________________ catalyzes the conversion of malatae to oxaloacetate in the CAC\>

Answer 40

Malate dehydrogenase

Question 41

\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_ ___________________ also known as Complex II of the electron transport chain; it is an integral membrane protein complex bound to the inner mitochondrial membrane that feeds electrons directly into the electron transport chain. It contains three different Fe-S clusters where electrons are passed from FADH2 to coenzuyme Q.

Answer 41

Succinate dehydrogenase

Question 42

Malate dehydrogenase is pro-\_\_\_\_ specific.

Answer 42

Pro-R

Question 43

Why is the oxidation of malate to oxaloacetate spontaneous under cellular conditions despite the standard free energy change being close to 30 kJ?

Answer 43

Because OAA is constantly being converted to citrate; therefore, the product is very low, pushing the reaction forward despite such a positive standard free energy change

Question 44

What are the three irreversible steps of the CAC?

Answer 44

1. Citrate synthase 2. Isocitrate dehydrogenase 3. Alpha-ketoglutarate dehydrogenase

Question 45

The CAC is controlled at the level of _________________ \_\_\_\_\_\_\_\_\_\_\_\_ at three points: transport of pyruvate into the mitochondria by the mitochondrial pyruvate carrier, the pyruvate dehydrogenase complex, and citrate synthase.

Answer 45

Pyruvate entry