MODULE 10: Chapter 10.2

Question 1

What is the role of pyruvate in cellular metabolism?

Answer 1

Pyruvate serves as a source of reducing power for the citrate cycle and as a precursor for glucose synthesis in gluconeogenesis.

Question 2

How is pyruvate transported into the mitochondria?

Answer 2

Pyruvate transport is accomplished by a transmembrane transporter protein.

Question 3

What enzyme catalyzes the conversion of pyruvate to acetyl-CoA?

Answer 3

Pyruvate dehydrogenase.

Question 4

What is the reaction mechanism of pyruvate dehydrogenase?

Answer 4

It involves a five-step reaction mechanism that requires three distinct enzymes and five different coenzymes.

Question 5

List the five coenzymes required for the pyruvate dehydrogenase reaction.

Answer 5

• NAD⁺
• FAD
• CoA
• Thiamine pyrophosphate (TPP)
• α-lipoic acid (lipoamide)

Question 6

What is NAD⁺ derived from?

Answer 6

NAD⁺ is derived from the water-soluble vitamin niacin, also called vitamin B3.

Question 7

What is the daily requirement of niacin for adults?

Answer 7

15–20 mg.

Question 8

What disease is caused by severe niacin deficiency?

Answer 8

Pellagra.

Question 9

What are the common symptoms of pellagra?

Answer 9

• Skin rash
• Diarrhea
• Neurologic problems (depression, memory loss)

Question 10

How does corn preparation affect niacin absorption?

Answer 10

Soaking corn in lime solution releases niacin from its protein-bound form, improving absorption.

Question 11

What vitamin is flavin adenine dinucleotide (FAD) derived from?

Answer 11

Riboflavin, also called vitamin B2.

Question 12

What is the primary function of FAD in metabolic reactions?

Answer 12

FAD serves as a coenzyme in redox reactions.

Question 13

What is the consequence of riboflavin deficiency?

Answer 13

Cheilosis, characterized by swelling and cracked lips.

Question 14

What is Coenzyme A (CoA) derived from?

Answer 14

Pantothenic acid, also called vitamin B5.

Question 15

What is the primary role of CoA?

Answer 15

To function as a carrier molecule for an acetyl group in the form of acetyl-CoA.

Question 16

What is thiamine pyrophosphate (TPP) derived from?

Answer 16

Thiamine, also called vitamin B1.

Question 17

What disease is caused by thiamine deficiency?

Answer 17

Beriberi.

Question 18

What are the symptoms of beriberi?

Answer 18

• Anorexia
• Cardiovascular problems
• Neurologic symptoms

Question 19

What is α-lipoic acid’s role in metabolic reactions?

Answer 19

To provide a reactive disulfide that can participate in redox reactions.

Question 20

What is the structure of Coenzyme A?

Answer 20

It consists of a central pantothenic acid unit linked to β-mercaptoethylamine and 3′-phosphoadenosine diphosphate.

Question 21

Fill in the blank: The acetyl group in acetyl-CoA is linked to CoA through a _______.

Answer 21

thioester bond.

Question 22

True or False: FAD can only accept two electrons at a time.

Answer 22

False.

Question 23

What is the average daily intake of pantothenic acid?

Answer 23

∼5 mg.

Question 24

What is the recommended dietary allowance of thiamine for adults?

Answer 24

∼1 mg.

Question 25

What covalent linkage forms a lipoamide in the pyruvate dehydrogenase complex?

Answer 25

α-lipoic acid is linked to a lysine ε amino group on the E2 subunit ## Footnote This linkage occurs in the dihydrolipoyl acetyltransferase.

Question 26

What is the first step in the pyruvate dehydrogenase reaction?

Answer 26

Pyruvate is decarboxylated by the E1 enzyme subunit to form hydroxyethyl-TPP and CO2.

Question 27

What is the end product of the pyruvate dehydrogenase reaction?

Answer 27

Acetyl-CoA.

Question 28

What is the role of α-lipoic acid in the pyruvate dehydrogenase complex?

Answer 28

It functions as a coenzyme and is involved in the transfer of acetyl groups.

Question 29

List the three different catalytic enzymes in the eukaryotic pyruvate dehydrogenase complex.

Answer 29

* E1: pyruvate dehydrogenase * E2: dihydrolipoyl acetyltransferase * E3: dihydrolipoyl dehydrogenase.

Question 30

True or False: α-Lipoic acid is considered a vitamin.

Answer 30

False.

Question 31

What are the two transiently associated coenzymes in the pyruvate dehydrogenase complex?

Answer 31

* CoA * NAD⁺.

Question 32

What is the approximate stoichiometry of the subunits in the pyruvate dehydrogenase complex?

Answer 32

E1:E2:E3 = 22:60:6.

Question 33

What structural feature allows the E2 subunit to transfer acetyl groups?

Answer 33

The lipoamide 'ball and chain' structure.

Question 34

Fill in the blank: The E2 amino-terminal segment consists of a ball, a chain, a pivot, and a _______.

Answer 34

linker.

Question 35

What is the role of arsenic in relation to pyruvate dehydrogenase?

Answer 35

Arsenic acts as an environmental inhibitor by forming adducts with dihydrolipoamide.

Question 36

What are the potential health effects of chronic arsenic exposure?

Answer 36

* Ulcerous skin lesions * Increased risk of cancers.

Question 37

What happens to lipoamide during arsenic poisoning?

Answer 37

The reduced lipoamide forms an adduct with arsenite, leading to inactivation.

Question 38

What is the overall reaction type for the conversion of pyruvate to acetyl-CoA?

Answer 38

Oxidative decarboxylation.

Question 39

How many amino acids compose the lipoamide 'ball and chain' structure?

Answer 39

146 amino acids.

Question 40

What is the function of coenzymes in the pyruvate dehydrogenase complex?

Answer 40

They provide a platform for the catalytic reactions.

Question 41

What is the significance of the E2 subunit's flexible segment?

Answer 41

It allows movement and facilitates the transfer of acetyl groups.

Question 42

True or False: The E3 subunit of the pyruvate dehydrogenase complex is also found in the α-ketoglutarate dehydrogenase complex.

Answer 42

True.

Question 43

What is the molecular mass of the pyruvate dehydrogenase complex?

Answer 43

Approximately 7800 kDa.

Question 44

What is produced during the reoxidation of E3-FADH2?

Answer 44

NADH + H⁺.

Question 45

What toxic element was found in drinking water that prompted massive purification efforts?

Answer 45

Arsenic ## Footnote Arsenic-contaminated drinking water has been found in Southeast Asia and South America, often near mined areas.

Question 46

What are the three metabolic fates of Acetyl-CoA?

Answer 46

* Metabolized by the citrate cycle to produce ATP * Stored as fatty acids in adipose tissue * Used for the synthesis of membrane lipids, cholesterol, and ketones

Question 47

Why is the pyruvate dehydrogenase reaction considered essentially irreversible?

Answer 47

Physiologic concentrations of reactants and products cannot overcome the biochemical standard free energy change (ΔG°′ = −33.4 kJ/mol)

Question 48

What regulates the activity of the pyruvate dehydrogenase complex?

Answer 48

Phosphorylation ## Footnote The phosphorylated form of pyruvate dehydrogenase is inactive.

Question 49

What effect do high NADH-to-NAD⁺ ratios have on pyruvate dehydrogenase activity?

Answer 49

NADH competes with NAD⁺ for binding to E3, reducing the efficiency of the complex.

Question 50

What happens when acetyl-CoA levels are high in the mitochondrial matrix?

Answer 50

They compete with CoA binding, reducing the efficiency of the E2 complex.

Question 51

Which enzyme phosphorylates the E1 subunit of pyruvate dehydrogenase?

Answer 51

Pyruvate dehydrogenase kinase

Question 52

What activates the enzyme pyruvate dehydrogenase phosphatase-1?

Answer 52

Calcium ions (Ca2⁺)

Question 53

What effect does increased NADH, acetyl-CoA, and ATP have on pyruvate dehydrogenase activity?

Answer 53

They activate pyruvate dehydrogenase kinase, leading to phosphorylation and inhibition of pyruvate dehydrogenase.

Question 54

What indicates a need to shift metabolic flux toward catabolic pathways?

Answer 54

Elevated levels of NAD⁺, CoA, ADP, and Ca2⁺

Question 55

What are coenzymes and why were they initially discovered as vitamins?

Answer 55

Biomolecules providing additional functional groups to enzymes; they are often not synthesized by all organisms and are required for key metabolic enzymes.

Question 56

How many coenzymes are required for the pyruvate dehydrogenase complex?

Answer 56

Five ## Footnote The coenzymes are TPP, lipoamide, CoA, FAD, and NAD⁺.

Question 57

What is the role of TPP in the pyruvate dehydrogenase reaction?

Answer 57

It functions in a decarboxylation reaction to convert pyruvate to CO2 and hydroxyethyl-TPP.

Question 58

What is the disease caused by a severe deficiency of niacin (vitamin B3)?

Answer 58

Pellagra

Question 59

What is the function of flavoproteins?

Answer 59

They require the coenzyme FAD or FMN for activity.

Question 60

What is the precursor of coenzyme A (CoA)?

Answer 60

Pantothenic acid (vitamin B5)

Question 61

What disease is caused by thiamine deficiency?

Answer 61

Beriberi

Question 62

What does α-lipoic acid (lipoamide) do?

Answer 62

It is a coenzyme carrier of acetyl groups and contains a reactive thiol group.