MODULE 9: Chapter 9.3

Question 1

What is glycolysis?

Answer 1

Glycolysis is a core metabolic pathway that converts glucose to pyruvate, generating ATP under anaerobic conditions.

It consists of 10 enzymatic reactions and occurs in the cytosol.

Question 2

What are the three primary reasons glycolysis is significant?

Answer 2

• Glycolytic enzymes are highly conserved among all living organisms
• It is the primary pathway for ATP generation under anaerobic conditions
• Metabolites of glycolysis serve as precursors for many interdependent pathways

This includes mitochondrial ATP synthesis.

Question 3

What does glycolysis accomplish for the cell?

Answer 3

Glycolysis generates ATP and produces pyruvate, which can be converted to acetyl-CoA, lactate, or ethanol.

This is critical for energy production, especially in anaerobic conditions.

Question 4

What is the overall net reaction of glycolysis?

Answer 4

Glucose + 2 NAD⁺ + 2 ADP + 2 Pi → 2 Pyruvate + 2 NADH + 2 ATP + 2 H₂O.

This reaction involves the conversion of one molecule of glucose into two molecules of pyruvate.

Question 5

What are the key enzymes in glycolysis?

Answer 5

• Hexokinase
• Phosphofructokinase-1
• Pyruvate kinase

Each enzyme plays a critical role in specific steps of the glycolytic pathway.

Question 6

How is hexokinase regulated?

Answer 6

Hexokinase is feedback inhibited by glucose-6-P.

This regulation helps control glucose phosphorylation.

Question 7

What activates phosphofructokinase-1?

Answer 7

AMP and fructose-2,6-bisphosphate activate phosphofructokinase-1.

It is inhibited by ATP and citrate.

Question 8

What is the significance of pyruvate kinase?

Answer 8

Pyruvate kinase catalyzes the final reaction in glycolysis and is activated by AMP and fructose-1,6-bisphosphate.

It is inhibited by ATP and acetyl-CoA.

Question 9

What is the role of glycolysis in blood glucose levels?

Answer 9

Glycolysis helps maintain appropriate blood glucose levels.

A deficiency in glucokinase can lead to MODY2 diabetes.

Question 10

What is the ATP yield from glycolysis under anaerobic conditions?

Answer 10

Glycolysis yields 2 net ATP molecules from one molecule of glucose.

This is significantly lower than the yield from aerobic respiration.

Question 11

What happens to pyruvate under aerobic conditions?

Answer 11

Pyruvate is oxidized to CO2 and H2O in the mitochondrial matrix, generating an additional 30 molecules of ATP.

This contributes to a total of 32 ATP from one glucose molecule.

Question 12

What are the two stages of glycolysis?

Answer 12

• Stage 1: ATP investment (reactions 1–5)
• Stage 2: ATP earnings (reactions 6–10)

These stages highlight the initial investment of ATP and subsequent production of ATP.

Question 13

What is the first step of glycolysis?

Answer 13

Hexokinase phosphorylates glucose to form glucose-6-phosphate.

This step requires ATP.

Question 14

What reaction does aldolase catalyze in glycolysis?

Answer 14

Aldolase catalyzes the cleavage of fructose-1,6-bisphosphate into glyceraldehyde-3-phosphate and dihydroxyacetone phosphate.

This is a key step in converting a six-carbon molecule into two three-carbon molecules.

Question 15

What is substrate-level phosphorylation?

Answer 15

Substrate-level phosphorylation is the direct production of ATP by transferring a phosphoryl group from a high-energy donor to ADP.

This occurs in glycolysis during specific reactions.

Question 16

Which enzymes in glycolysis have large negative ΔG values?

Answer 16

• Hexokinase
• Phosphofructokinase-1
• Pyruvate kinase

These reactions are considered irreversible under physiological conditions.

Question 17

What is the significance of the ΔG values in glycolysis?

Answer 17

The ΔG values help identify critical steps in the pathway that drive product formation.

Large negative values indicate irreversible reactions.

Question 18

What type of reactions are primarily involved in glycolysis?

Answer 18

Glycolysis involves bond rearrangements, phosphoryl transfer reactions, isomerizations, an aldol cleavage, an oxidation, and a dehydration.

These reactions contribute to the overall conversion of glucose to pyruvate.

Question 19

What is the first reaction in glycolysis?

Answer 19

Phosphorylation of Glucose by Hexokinase or Glucokinase

Question 20

What product is generated from the phosphorylation of glucose?

Answer 20

Glucose-6-P

Question 21

Which enzymes catalyze the phosphorylation of glucose?

Answer 21

• Hexokinase
• Glucokinase

Question 22

What is the role of Mg2⁺ in the phosphorylation reaction?

Answer 22

It shields negative charges in the ATP molecule

Question 23

How does hexokinase differ from glucokinase?

Answer 23

• Hexokinase: found in all cells, broad substrate specificity
• Glucokinase: present only in liver and pancreatic cells, highly specific for glucose

Question 24

What inhibits hexokinase activity?

Answer 24

Glucose-6-P

Question 25

What is the second reaction in glycolysis?

Answer 25

Isomerization of Glucose-6-P to Fructose-6-P by Phosphoglucoisomerase

Question 26

What type of reaction is catalyzed by phosphoglucoisomerase?

Answer 26

Interconversion of an aldose and a ketose

Question 27

What is the free energy change for the isomerization of glucose-6-P to fructose-6-P?

Answer 27

ΔG = -2.9 kJ/mol

Question 28

What is the third reaction in glycolysis?

Answer 28

Phosphorylation of Fructose-6-P to Fructose-1,6-BP by Phosphofructokinase-1

Question 29

What is the significance of the reaction catalyzed by phosphofructokinase-1?

Answer 29

It serves as a major regulatory site in the pathway

Question 30

What is the free energy change for the phosphorylation of fructose-6-P?

Answer 30

ΔG = -18.8 kJ/mol

Question 31

What regulates phosphofructokinase-1 activity?

Answer 31

* AMP * ADP (positive effectors) * ATP (negative effector)

Question 32

What is the fourth reaction in glycolysis?

Answer 32

Cleavage of Fructose-1,6-BP into Glyceraldehyde-3-P and Dihydroxyacetone-P by Aldolase

Question 33

What does the term 'lysis' refer to in glycolysis?

Answer 33

Splitting

Question 34

What is the mechanism of aldolase in the cleavage reaction?

Answer 34

Formation of a covalent enzyme–substrate complex through a Schiff base

Question 35

What are the products of the cleavage of fructose-1,6-BP?

Answer 35

* Glyceraldehyde-3-P * Dihydroxyacetone-P

Question 36

What is the fifth reaction in glycolysis?

Answer 36

Isomerization of Dihydroxyacetone-P to Glyceraldehyde-3-P by Triose Phosphate Isomerase

Question 37

What problem does the production of dihydroxyacetone-P create?

Answer 37

Only glyceraldehyde-3-P is the substrate for the next reaction

Question 38

What occurs in stage 1 of glycolysis?

Answer 38

ATP investment and production of phosphorylated compounds

Question 39

What is the net ATP yield from glycolysis after stage 1 and stage 2?

Answer 39

2 ATP per glucose

Question 40

What is the main outcome of stage 2 of glycolysis?

Answer 40

ATP earnings through substrate-level phosphorylation

Question 41

What is the sixth reaction in glycolysis?

Answer 41

Oxidation and Phosphorylation of Glyceraldehyde-3-P to Form 1,3-Bisphosphoglycerate by Glyceraldehyde-3-P Dehydrogenase

Question 42

What is required for the glyceraldehyde-3-P dehydrogenase reaction to proceed?

Answer 42

A constant supply of NAD⁺

Question 43

What happens to NADH produced in glycolysis under anaerobic conditions?

Answer 43

It is oxidized by lactate dehydrogenase to form lactate

Question 44

What is the final product of glycolysis?

Answer 44

Pyruvate

Question 45

True or False: Reaction 10 in glycolysis is reversible.

Answer 45

False

Question 46

Fill in the blank: The difference between ΔG°′ and ΔG values indicates the ________ of a reaction under cellular conditions.

Answer 46

favorability

Question 47

What two high-energy phosphoryl compounds are required for gluconeogenesis?

Answer 47

ATP and GTP

Question 48

What is the product of the oxidation and phosphorylation of glyceraldehyde-3-P?

Answer 48

1,3-bisphosphoglycerate

Question 49

Which enzyme catalyzes the reaction that forms 1,3-bisphosphoglycerate from glyceraldehyde-3-P?

Answer 49

Glyceraldehyde-3-P dehydrogenase

Question 50

What coenzyme is required for the oxidation step in the reaction forming 1,3-bisphosphoglycerate?

Answer 50

NAD⁺

Question 51

What must be continually replenished in the cytosol to maintain flux through glycolysis?

Answer 51

NAD⁺

Question 52

What are the four steps of the enzyme mechanism for glyceraldehyde-3-P dehydrogenase?

Answer 52

* Binding of glyceraldehyde-3-P to the enzyme * Dehydrogenation of the aldehyde group * Release of NADH and regeneration of NAD⁺ * Nucleophilic attack by phosphate ion

Question 53

What is the standard free energy of hydrolysis for 1,3-bisphosphoglycerate?

Answer 53

−49.4 kJ/mol

Question 54

What is the standard free energy of hydrolysis for ATP?

Answer 54

−30.5 kJ/mol

Question 55

What accounts for the large favorable free energy change for phosphate hydrolysis of 1,3-bisphosphoglycerate?

Answer 55

Resonance stabilization of the product 3-phosphoglycerate

Question 56

What is the biochemical standard free energy change for phosphoenolpyruvate?

Answer 56

−61.9 kJ/mol

Question 57

What does the high phosphoryl transfer energy in 1,3-bisphosphoglycerate allow?

Answer 57

Phosphorylation of ADP to generate ATP

Question 58

Which enzyme catalyzes the conversion of 1,3-bisphosphoglycerate to 3-phosphoglycerate?

Answer 58

Phosphoglycerate kinase

Question 59

How many ATP molecules are generated from one molecule of glucose during glycolysis?

Answer 59

2 ATP

Question 60

What structural feature do phosphoglycerate kinase and hexokinase share?

Answer 60

They have two lobes, each binding a substrate molecule

Question 61

What is the actual change in free energy for reactions 6 and 7?

Answer 61

Close to zero (ΔG ₌ −1.3 kJ/mol; ΔG ₌ −3.4 kJ/mol)

Question 62

Which three enzymes in glycolysis catalyze irreversible reactions?

Answer 62

* Hexokinase * Phosphofructokinase-1 * Pyruvate kinase

Question 63

What is the side reaction involving 1,3-bisphosphoglycerate in erythrocytes?

Answer 63

Conversion to 2,3-bisphosphoglycerate (2,3-BPG)

Question 64

What is the role of 2,3-bisphosphoglycerate in erythrocytes?

Answer 64

It is an allosteric regulator of hemoglobin

Question 65

What does the presence of defects in glycolytic enzymes affect regarding oxygen transport?

Answer 65

Levels of 2,3-BPG

Question 66

What is the purpose of reaction 8 in glycolysis?

Answer 66

To generate 2-phosphoglycerate

Question 67

What enzyme catalyzes the reaction that forms 2-phosphoglycerate from 3-phosphoglycerate?

Answer 67

Phosphoglycerate mutase

Question 68

What type of reaction does phosphoglycerate mutase catalyze?

Answer 68

Isomerization reaction

Question 69

What is the mechanism of the phosphoglycerate mutase reaction based on?

Answer 69

Phosphoryl transfer from a phosphorylated histidine residue

Question 70

What is the product formed from the dehydration of 2-phosphoglycerate?

Answer 70

Phosphoenolpyruvate

Question 71

What enzyme catalyzes the dehydration of 2-phosphoglycerate to form phosphoenolpyruvate?

Answer 71

Enolase

Question 72

What reaction does enolase catalyze in glycolysis?

Answer 72

The conversion of 2-phosphoglycerate to phosphoenolpyruvate through a dehydration reaction ## Footnote This reaction increases the phosphoryl transfer potential of the triose sugar.

Question 73

What is the standard free energy change (ΔG°′) for the conversion of 2-phosphoglycerate to phosphoenolpyruvate?

Answer 73

ΔG°′ = +1.7 kJ/mol ## Footnote This indicates that the overall metabolic energy available from 2-phosphoglycerate or phosphoenolpyruvate is similar.

Question 74

What is the significance of the enol form generated by enolase?

Answer 74

It traps the phosphoryl group in an unstable form, dramatically increasing the phosphoryl transfer potential ## Footnote The biochemical standard free energy change for phosphate hydrolysis of 2-phosphoglycerate is ΔG°′ = -17.6 kJ/mol, while for phosphoenolpyruvate it is ΔG°′ = -61.9 kJ/mol.

Question 75

What is substrate-level phosphorylation?

Answer 75

A mechanism for ATP production through the direct transfer of a phosphoryl group from a high-energy donor to ADP ## Footnote This process is independent of ATP synthase.

Question 76

Which enzymes catalyze the substrate-level phosphorylation reactions in glycolysis?

Answer 76

Phosphoglycerate kinase and pyruvate kinase ## Footnote These enzymes transfer phosphoryl groups from substrates with high biochemical standard free energy changes.

Question 77

How many ATP are generated from glycolysis per glucose molecule under anaerobic conditions?

Answer 77

Net yield of 2 ATP ## Footnote This accounts for the 2 ATP invested in the initial stages of glycolysis.

Question 78

What is the role of pyruvate kinase in glycolysis?

Answer 78

It catalyzes the conversion of phosphoenolpyruvate and ADP to pyruvate and ATP ## Footnote This is the second substrate-level phosphorylation reaction in glycolysis.

Question 79

What is the overall standard change in free energy (ΔG°′) for the glycolytic pathway?

Answer 79

The specific value is not provided in the text ## Footnote The overall actual change in free energy (ΔG) for the glycolytic pathway also needs to be determined.

Question 80

What is the key function of phosphoenolpyruvate in glycolysis?

Answer 80

It has a high phosphoryl transfer potential used to generate ATP ## Footnote This potential is exploited in the reaction catalyzed by pyruvate kinase.

Question 81

True or False: Pyruvate is a stable compound in cells.

Answer 81

True ## Footnote Pyruvate is used by many other metabolic pathways.

Question 82

Fill in the blank: The enzyme _______ catalyzes the conversion of glucose to glucose-6-phosphate.

Answer 82

hexokinase ## Footnote Hexokinase is a key enzyme in glycolysis.

Question 83

Fill in the blank: The enzyme _______ converts fructose-6-phosphate to fructose-1,6-bisphosphate.

Answer 83

phosphofructokinase-1 ## Footnote This enzyme is a key regulated enzyme in the glycolytic pathway.