Chapter 14: Regulation of Glycolysis and Gluconeogenesis Flashcards

1
Q

Insulin favors

A
  • Glycolysis
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2
Q

Glucagon favors

A
  • Gluconeogenesis
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3
Q

Fructose-2,6-bisphosphate

A
  • Activates PFK-1

- WORKS AS A KINASE OR PHOSPHATASE

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4
Q

In the fed state

A
  • Insulin/glucagon ration is high

- Use insulin to convert glucose to storage, glycogen

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5
Q

In the starving state

A
  • Insulin/glucagon ratio is low
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6
Q

Substrate (futile) cycling

A
  • Occurs where two opposing enzymes are active at the same time
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7
Q

Glucokinase

A
  • Very specific for glucose but has a high km (not saturated)
  • Not inhibited by G-6-P
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8
Q

Glucose-6-phsphate and products

A
  • Allosterically inhibit hexokinase
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9
Q

Hexokinase inhibited by

A
  • Fructose-6-phosphate

- Overcome by fructose-1-phosphate

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10
Q

F2,6BP is produced by a bifunctional enzyme

A
  • PFK-2

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

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11
Q

PFK-1 is a large oligomeric enzyme

A
  • Catalyzes the first irreversible reaction that is UNIQUE to the glycolytic pathway
  • The committed step
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12
Q

ATP in glycolytic pathways

A
  • Acts as both a substrate and inhibitor

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

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13
Q

Citrate inhibits

A
  • PFK-1
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14
Q

Fructose-2,6-bisphosphate

A
  • Most potent allosteric activator of PFK-1
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15
Q

Allosteric activators of PFK-1

A
  • ADP
  • AMP
  • Fructose-2,6,-bisphosphate
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16
Q

Allosteric inhibitors of PFK-1

A
  • ATP

- Citrate

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17
Q

Fructose-1,6-bisphosphatase inhibits

A
  • PFK-1 activity
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18
Q

Activation by F-1,6-BP

A
  • Feed forward activation

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

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19
Q

Alanine production

A
  • Produced by proteolysis
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20
Q

Hepatic pyruvate kinase by protein kinase A

A
  • Glucagon stimulated phosphorylation (inactivation)
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21
Q

Control of pyruvate kinase activity by reversible phosphorylation

A
  • Glucagon signals the fasting state
  • Causes phosphorylation
  • Turns off pyruvate kinase (glycolysis will be off)
22
Q

Pyruvate kinase is activated by

A
  • Fructose-1,6-bisphosphate
23
Q

When glucose is in short supply

A
  • Glucagon is secreted from the alpha cells of the pancreas
24
Q

Low blood sugar levels

A
  • Glucagon is secreted

- Receptor mediated activation of protein kinase A inhibits pyruvate kinase

25
Q

Glucagon mediated phosphorylation

A
  • Inhibits pyruvate kinase
26
Q

Pyruvate carboxylase

A
  • Helps bypass the pyruvate kinase step in glycolysis
  • Mitochondrial enzyme
  • Allosteric control
  • Requires Acetyl-SCoA
27
Q

Fructose-2,6-bisphosphate

A
  • Produced by a bifunctional enzyme
  • Not a glycolytic intermediate
  • Most potent activator of glycolysis
  • Inhibits gluconeogenesis
28
Q

Fructose-2,6-bisphosphate bifunctional enzymatic activity

A
  • Works as a kinase and phosphatase
  • Phosphofructokinase 2
  • Under allosteric and hormonal control
29
Q

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

A
  • Increasing affinity for substrate
  • Reducing inhibitory effect of ATP
  • Favors T –> R transition
30
Q

Phosphorylation of kinase

A
  • Turns it off

- Causes it to work as a phosphatase

31
Q

F6P is a substrate for the kinase

A
  • Activates glycolysis
32
Q

Low blood sugar level favors glucagon

A
  • Phosphorylates things
  • Bifuncitonal enzyme
  • Reduces glycolytic flux
33
Q

Hormones (endocrine mechanism)

A
  • Can effect the amount of enzyme produced

- Induction or repression

34
Q

Endocrine mechanisms

A
  • Cause covalent modification, thus altering activity
35
Q

Secretion of insulin

A
  • 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
36
Q

Insulin induction

A
  • Glucokinase (liver)
  • PFK-1
  • Pyruvate kinase
37
Q

Insulin repression

A
  • G-6-Pase
  • PEP carboxylase
  • FBPase-1
  • Pyruvate carboxylase
38
Q

Induction of gluconeogenic enzymes during periods of starvation

A
  • G-6-Pase
  • PEP carboxykinase
  • FBPase-1
  • Pyruvate carboxylase
39
Q

Low glucose levels increase gluconeogenesis via

A
  • Glucagon-mediated covalent modification
40
Q

Glucagon secreted from alpha cells in response to

A
  • Low glucose

- Inhibits glycolysis

41
Q

Pyruvate kinase A (PrK A) mediated phosphorylation

A
  • Favors phosphatase activity of bifunctional enzyme

- Reduces F-2,6-BP levels

42
Q

Glucagon generally causes

A
  • Phosphorylation
43
Q

Insulin generally causes

A
  • Dephosphorylation
44
Q

With dephosphorylation

A
  • Kinase activity of the bifunctional enzyme is favored
45
Q

With phosphorylation

A
  • Phosphatase activity of bifunctional enzyme is favored
46
Q

Glucagon stimulates

A
  • Phosphorylation

- Inactivation of the hepatic PFK-2

47
Q

Transcription of the gene for PEP carboxykinase

A
  • Promoted by glucagon

- Opposed by insulin

48
Q

Cortisol

A
  • Can induce gluconeogenic enzymes

- Opposes the action of insulin

49
Q

Steroid hormones

A
  • Interact with nuclear or cytoplasmic receptors
  • Alter enzyme synthesis
  • Promote protein catabolism (increases amino acid availability for gluconeogenesis)
50
Q

Fructose-2,6-bisonosphate inhibits

A
  • Bisphosphatase activity of gluconeogenesis