Chapter 14: Regulation of Glycolysis and Gluconeogenesis

Question 1

Insulin favors

Answer 1

• Glycolysis

Question 2

Glucagon favors

Answer 2

• Gluconeogenesis

Question 3

Fructose-2,6-bisphosphate

Answer 3

• Activates PFK-1

- WORKS AS A KINASE OR PHOSPHATASE

Question 4

In the fed state

Answer 4

• Insulin/glucagon ration is high

- Use insulin to convert glucose to storage, glycogen

Question 5

In the starving state

Answer 5

• Insulin/glucagon ratio is low

Question 6

Substrate (futile) cycling

Answer 6

• Occurs where two opposing enzymes are active at the same time

Question 7

Glucokinase

Answer 7

• Very specific for glucose but has a high km (not saturated)
• Not inhibited by G-6-P

Question 8

Glucose-6-phsphate and products

Answer 8

• Allosterically inhibit hexokinase

Question 9

Hexokinase inhibited by

Answer 9

• Fructose-6-phosphate

- Overcome by fructose-1-phosphate

Question 10

F2,6BP is produced by a bifunctional enzyme

Answer 10

• PFK-2

- As a kinase produces F2,6BP (activator of PFK I)

Question 11

PFK-1 is a large oligomeric enzyme

Answer 11

• Catalyzes the first irreversible reaction that is UNIQUE to the glycolytic pathway
• The committed step

Question 12

ATP in glycolytic pathways

Answer 12

• Acts as both a substrate and inhibitor

- Increases the Km of PFK-1 for substrate, inhibiting the enzyme (AMP overcomes inhibition)

Question 13

Citrate inhibits

Answer 13

• PFK-1

Question 14

Fructose-2,6-bisphosphate

Answer 14

• Most potent allosteric activator of PFK-1

Question 15

Allosteric activators of PFK-1

Answer 15

• ADP
• AMP
• Fructose-2,6,-bisphosphate

Question 16

Allosteric inhibitors of PFK-1

Answer 16

• ATP

- Citrate

Question 17

Fructose-1,6-bisphosphatase inhibits

Answer 17

• PFK-1 activity

Question 18

Activation by F-1,6-BP

Answer 18

• Feed forward activation

- Second most common enzymopathy in humans (after glucose-6-phosphate dehydrogenase)

Question 19

Alanine production

Answer 19

• Produced by proteolysis

Question 20

Hepatic pyruvate kinase by protein kinase A

Answer 20

• Glucagon stimulated phosphorylation (inactivation)

Question 21

Control of pyruvate kinase activity by reversible phosphorylation

Answer 21

• Glucagon signals the fasting state
• Causes phosphorylation
• Turns off pyruvate kinase (glycolysis will be off)

Question 22

Pyruvate kinase is activated by

Answer 22

• Fructose-1,6-bisphosphate

Question 23

When glucose is in short supply

Answer 23

• Glucagon is secreted from the alpha cells of the pancreas

Question 24

Low blood sugar levels

Answer 24

• Glucagon is secreted

- Receptor mediated activation of protein kinase A inhibits pyruvate kinase

Question 25

Glucagon mediated phosphorylation

Answer 25

- Inhibits pyruvate kinase

Question 26

Pyruvate carboxylase

Answer 26

- Helps bypass the pyruvate kinase step in glycolysis - Mitochondrial enzyme - Allosteric control - Requires Acetyl-SCoA

Question 27

Fructose-2,6-bisphosphate

Answer 27

- Produced by a bifunctional enzyme - Not a glycolytic intermediate - Most potent activator of glycolysis - Inhibits gluconeogenesis

Question 28

Fructose-2,6-bisphosphate bifunctional enzymatic activity

Answer 28

- Works as a kinase and phosphatase - Phosphofructokinase 2 - Under allosteric and hormonal control

Question 29

Allosteric activation of PFK-1 by F-2,6-BP

Answer 29

- Increasing affinity for substrate - Reducing inhibitory effect of ATP - Favors T --> R transition

Question 30

Phosphorylation of kinase

Answer 30

- Turns it off | - Causes it to work as a phosphatase

Question 31

F6P is a substrate for the kinase

Answer 31

- Activates glycolysis

Question 32

Low blood sugar level favors glucagon

Answer 32

- Phosphorylates things - Bifuncitonal enzyme - Reduces glycolytic flux

Question 33

Hormones (endocrine mechanism)

Answer 33

- Can effect the amount of enzyme produced | - Induction or repression

Question 34

Endocrine mechanisms

Answer 34

- Cause covalent modification, thus altering activity

Question 35

Secretion of insulin

Answer 35

- Positive post prandially (the fed state) - Increases all anabolic pathways that decrease blood glucose levels - Induces the irreversible enzymes in the glycolytic pathway - Represses the enzymes in the gluconeogenic pathway

Question 36

Insulin induction

Answer 36

- Glucokinase (liver) - PFK-1 - Pyruvate kinase

Question 37

Insulin repression

Answer 37

- G-6-Pase - PEP carboxylase - FBPase-1 - Pyruvate carboxylase

Question 38

Induction of gluconeogenic enzymes during periods of starvation

Answer 38

- G-6-Pase - PEP carboxykinase - FBPase-1 - Pyruvate carboxylase

Question 39

Low glucose levels increase gluconeogenesis via

Answer 39

- Glucagon-mediated covalent modification

Question 40

Glucagon secreted from alpha cells in response to

Answer 40

- Low glucose | - Inhibits glycolysis

Question 41

Pyruvate kinase A (PrK A) mediated phosphorylation

Answer 41

- Favors phosphatase activity of bifunctional enzyme | - Reduces F-2,6-BP levels

Question 42

Glucagon generally causes

Answer 42

- Phosphorylation

Question 43

Insulin generally causes

Answer 43

- Dephosphorylation

Question 44

With dephosphorylation

Answer 44

- Kinase activity of the bifunctional enzyme is favored

Question 45

With phosphorylation

Answer 45

- Phosphatase activity of bifunctional enzyme is favored

Question 46

Glucagon stimulates

Answer 46

- Phosphorylation | - Inactivation of the hepatic PFK-2

Question 47

Transcription of the gene for PEP carboxykinase

Answer 47

- Promoted by glucagon | - Opposed by insulin

Question 48

Cortisol

Answer 48

- Can induce gluconeogenic enzymes | - Opposes the action of insulin

Question 49

Steroid hormones

Answer 49

- Interact with nuclear or cytoplasmic receptors - Alter enzyme synthesis - Promote protein catabolism (increases amino acid availability for gluconeogenesis)

Question 50

Fructose-2,6-bisonosphate inhibits

Answer 50

- Bisphosphatase activity of gluconeogenesis