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SMP - MNE Exam 2 > Lecture 26: Gluconeogenesis > Flashcards

Lecture 26: Gluconeogenesis Flashcards

1
Q

What are the 2 main metabolic priorities of our bodies?

A
  1. Make sure the brain has enough fuel

2. Make sure we’re not breaking down to much protein in our muscles = avoiding too many AA catabolism for gluconeo

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2
Q

3 mechanism to maintain blood glucose levels?

A
  1. Eating
  2. Glycogen synthesis/breakdown
  3. Gluceoneo
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3
Q

What 2 organs can perform gluconeo? % of where it happens?

A
  1. Liver: 90%

2. Kidneys: 10%

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4
Q

What are the possible starting materials for gluconeo?

A
  1. Pyruvate from lactate
  2. Glycerol (small amounts during fasting state)
  3. TCA cycle intermediates (which can be formed by glucogenic AAs)
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5
Q

How do adipocytes contribute to gluconeo?

A

They break down TAGs to free glycerol:
1. Can convert all the way up to DHAP but process stops there
OR
2. Liberate a ton of it for the liver/kidneys to perform full gluconeo

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6
Q

How is glycerol converted to DHAP? 2 steps

A
  1. Glycerol kinase: glycerol + ATP = glycerol-3-P + ADP (only in kidneys/liver)
  2. Glycerol-phosphate dehydrogenase: glycerol-3-P + NAD+ = DHAP + NADH
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7
Q

What do the 3 bypasses of gluconeo accomplish?

A
  1. Add Cs to make glucose

2. Reduce molecules to give glucose its reducing power

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8
Q

How much ATP does gluconeogenesis use compared to the energy created by glycolysis?

A

It uses up more energy than glycolysis provides (6 used vs 2 in glycolysis)

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9
Q

What are the 2 inhibitors of pyruvate kinase? Explain how each works.

A
  1. Alanine: allosteric inhibition

2. Glucagon/catecholamines: cAMP/PKA phosphorylation of pyruvate kinase = decreased activity

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10
Q

Gluconeo Step 1: Reactant/Products? Include # of Cs.

A

Pyruvate (3C) + HCO3- + ATP => Oxaloacetate + ADP + Pi

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11
Q

Gluconeo Step 1: Reaction type? 2 answers

A
  1. Carboxylation

2. Anaplerotic because provides a TCA intermediates thereby the TCA rate

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12
Q

Where does the pyruvate in Step 1 of gluconeo come from?

A
  1. Cytosol
  2. Alanine
  3. Lactic acid
  4. Glucogenic AAs: glutamate, aspartate among others
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13
Q

What are alpha keto acids? What is their purpose?

A

AAs without the amino group (replaced by another carboxyl group) that will feed into other pathways

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14
Q

How is pyruvate generated from alanine?

A

Alanine + alpha ketoglutarate = pyruvate + glutamate

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15
Q

What is the glucose-alanine cycle? 5 steps

A
  1. Glucose converted to pyruvate in muscle
  2. Pyruvate converted to alanine via aminotransferase
  3. Alanine is delivered from the muscle during starvation to the liver
  4. Liver converts it to glucose through gluconeo
  5. Glucose goes back to muscle for protein formation and energy
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16
Q

What is the Cori cycle?

A
  1. Lactate formed in muscles during anaerobic metabolism of glucose is sent to the liver
  2. Liver converts it to glucose through gluconeo
  3. Glucose goes back to muscle for protein formation and energy
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17
Q

How is lactate converted to pyruvate?

A

Lactate dehydrogenase: lactate + NAD+ => pyruvate + NADH

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18
Q

Which conversion to pyruvate is faster: AAs or lactate? Why is this a good thing?

A

Lactate

Good to avoid muscle wasting during fasting

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19
Q

Gluconeo Step 1: Enzyme?

A

Pyruvate carboxylase

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20
Q

What is pyruvate carboxylase regulated by?

A

Acetyl CoA: high levels activate it, low levels inhibit it (allosteric regulation)

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21
Q

Gluconeo Step 1: Cofactors?

A
  1. ATP

2. Biotin

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22
Q

Gluconeo Step 2: Reactant/Products? Include # of Cs.

A

Oxaloacetate (4C) + NADH => Malate (4C) + NAD+

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23
Q

Gluconeo Step 2: Purpose?

A

Get oxaloacetate out of the mitosol! Malate shuttle.

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24
Q

Gluconeo Step 4: Reactant/Products? Include # of Cs.

A

Malate (4C) + NAD+ => Oxaloacetate (4C) + NADH

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25
Q

Gluconeo Step 3?

A

Malate transport from mitosol to cytosol

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26
Q

Gluconeo Step 5: Reactant/Products? Include # of Cs.

A

Oxaloacetate (4C) + GTP => Phosphoenolpyruvate (3C) + GDP + CO2

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27
Q

Gluconeo Step 5: Reversible or irreversible?

A

Reversible

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28
Q

Where does gluconeo step 5 happen?

A

Can happen either in mitosol or cytosol

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29
Q

Gluconeo Step 5: Enzyme?

A

Cytosolic/Mitochondrial PEP carboxykinase

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30
Q

Gluconeo Step 5: Cofactor?

A

GTP

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31
Q

Where is PEPCK present?

A
  1. Liver
  2. Kidneys
  3. Adipocytes
  4. Muscles
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32
Q

Where is pyruvate carboxylase found?

A
  1. Liver
  2. Kidneys
  3. Adipocytes
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33
Q

What is the purpose of having PEPCK in muscles? When is this most useful?

A

Performs reverse reaction as a key anaplerotic reaction which is key in muscles during high physical activity during which energy is needed

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34
Q

What happens after mitochondrial PEPCK converts oxaloacetate to PEP? In which cases does this happen?

A

PEP can cross mito membrane

Happens when we obtained pyruvate from lactate, which already provided an NADH, so no need to use the malate shuttle

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35
Q

Gluconeo Step 6: Enzyme?

A

Enolase

36
Q

Gluconeo Step 6: Reactant/Products? Include # of Cs.

A

Phosphoenolpyruvate (3C) + H2O => 2-phosphoglycerate (3C)

37
Q

Gluconeo Step 7: Enzyme?

A

Phosphoglycerate mutase

38
Q

Gluconeo Step 7: Reactant/Products? Include # of Cs.

A

2-phosphoglycerate (3C) => 3-phosphoglycerate (3C)

39
Q

Gluconeo Step 8: Enzyme?

A

Phosphoglycerate kinase

40
Q

Gluconeo Step 8: Reactant/Products? Include # of Cs.

A

3-phosphoglycerate (3C) + ATP => 1,3BPG (3C) + ADP

41
Q

Gluconeo Step 9: Enzyme?

A

Glyceraldehyde-3-Phosphate Dehydrogenase (GAPDH)

42
Q

Gluconeo Step 9: Reactant/Products? Include # of Cs.

A

1,3-bisphosphoglycerate (3C) + NADH + H+ => GAP (3C) + Pi + NAD+

43
Q

Gluconeo Step 10: Enzyme?

A

TPI

44
Q

Gluconeo Step 10: Reactant/Products? Include # of Cs.

A

DHAP (3C) => GAP (3C)

45
Q

Gluconeo Step 11: Enzyme?

A

Aldolase

46
Q

Gluconeo Step 11: Reactant/Products? Include # of Cs.

A

DHAP (3C) + GAP (3C) => F1,6BP (6C)

47
Q

Gluconeo Step 12: Enzyme?

A

Fructose-1,6-bisphosphatase

48
Q

Gluconeo Step 12: Reactant/Products? Include # of Cs.

A

F1,6BP (6C) => F6P (6C) + Pi

49
Q

What is fructose-1,6-bisphosphatase stimulated by?

A
  1. Absence of F26BP

2. Glucagon/cAMP

50
Q

What do we call F-2,6-BP in regards to its effect on fructose-1,6-bisphosphatase?

A

An allosteric effector

51
Q

How are levels of F-2,6-BP downregulated?

A

Glucagon/epi activate PKA to phosphorylate Fructose-2 bisphosphatase (FBPase-2), activating it, which dephosphorylates F-2,6-BP

52
Q

Explain how PFK2 is regulated when blood glucose is high?

A

Insulin stimulates dephosphorylation of PKA (inactive) and phosphoprotein phosphatase (active) –> PP-1 dephosphorylates PFK2 –> activates it –> converts F-6P to F-2,6-BP –> stimulates PFK

53
Q

Explain how PFK2 is regulated when blood glucose is low?

A

Glucagon phosphorylates PKA (active) –> PKA phosphorylates PFK2 (inactive) –> activating the FBPase2 –> dephosphorylates F-2,6-BP to F-6P –> PFK not activated

54
Q

Gluconeo Step 13: Reactant/Products? Include # of Cs.

A

F6P (6C) => G6P (6C)

55
Q

Gluconeo Step 13: Enzyme?

A

Phosphohexose isomerase

56
Q

Gluconeo Step 14: Reactant/Products? Include # of Cs.

A

G6P (6C) => Glucose (6C) + Pi

57
Q

Gluconeo Step 14: Enzyme?

A

G6P phosphatase

58
Q

Where does the NADH and ATP/GTP for gluconeo come from? What happens when this runs out?

A

TAGs => FFAs => Beta oxidation => Acetyl-CoA + Increased rate of TCA because of intermediates formed by gluconeo => NADH/ATP/GTP
When TCA cannot keep up: ketogenesis!

59
Q

AA catabolism Step 1: Reactant/Products?

A

AA + alpha-ketoglutarate => alpha keto acid + glutamate

60
Q

How does starvation affect the rate of step 1 of AA catabolism? What is the purpose of this?

A

TCA cycle rate increased => less alpha-ketoglutarate available to accept amino group => lower rate of AA catabolism
Purpose: avoid muscle wasting during starvation

61
Q

AA catabolism Step 1: Enzyme?

A

Aminotransferase

62
Q

AA catabolism Step 1: Cofactor? Role?

A

Pyridoxal phosphate (PLP) (VB6 derivative): conduit to accept amino group

63
Q

What is the precursor to pyridoxal phosphate?

A

Vitamin B6

64
Q

AA catabolism Step 2: Reactant/Products?

A

Glutamate + H2O + NADP/NAD+ => alpha-ketoglutarate + NADPH/NADH + NH4+

65
Q

AA catabolism Step 2: Enzyme?

A

Glutamate dehydrogenase

66
Q

Gluconeo Step 2: Enzyme?

A

Malate dehydrogenase

67
Q

Gluconeo Step 4: Enzyme?

A

Malate dehydrogenase

68
Q

Other than glutamate, what is another good nitrogen donor? Describe the reaction. Where is this enzyme found?

A

Glutaminase: glutamine + H2O => glutamate + NH4+

Liver and kidney

69
Q

Which steps of gluconeo happen in the mitochondria?

A

1 and 2

Optional: 4 and 5

70
Q

Why else is malate transport from mitosol to the cytosol important (other than transporting oxaloacetate out)?

A

It transports NADH out which is needed for gluconeo!

71
Q

Under what conditions do steps 4 and 5 of gluconeo happen in the mitosol?

A

When the pyruvate source is lactate because NADH has already been generated in the cytosol by lactate dehydrogenase

72
Q

Where is the enzyme glucose-6-phosphatase found in the liver cells?

A

The ER

73
Q

What is the deamination of AAs limited by? Purpose of this?

A

The availability of alpha-ketoglutarate, which is a TCA intermediate
Starvation: low TCA intermediates so slows down AA degradation: PREVENTS MUSCLE WASTING

74
Q

AA catabolism Step 2: Cofactor?

A

NADP OR NAD+ (rare enzyme that can use both)

75
Q

AA catabolism Step 1: Reactant/Products?

A

Amino acid + alpha-ketoglutarate => alpha-keto acid + glutamate

76
Q

Can FAs be used for gluconeogenesis?

A

Odd numbered ones can because propionyl-CoA converted to succinyl-CoA

77
Q

Where does AA catabolism happen?

A

Mitosol

78
Q

What are the 2 types of malate dehydrogenases and what are they used for?

A
  1. Mitochondrial: TCA cycle AND gluconeogenesis (oxaloacetate to malate)
  2. Cytosolic: gluconeogenesis
79
Q

Where does the conversion of oxaloacetate to malate happen?

A

Mitochondria

80
Q

Where does the conversion of malate to oxaloacetate happen?

A

Both cytosol and mitosol

81
Q

What is the exact definition of a cofactor?

A

Substance (other than the substrate) whose presence is essential for the activity of an enzyme

82
Q

What is fructose-1,6-bisphosphatase inhibited by?

A
  1. AMP

2. High levels of fructose-2,6-BP

83
Q

What is the major source for gluconeo during the fasting state?

A

AAs

84
Q

When is glycerol used in gluconeo?

A

Starvation

85
Q

What is the main anaplerotic enzyme in the kidney?

A

Pyruvate carboxylase

86
Q

Which is the only AA that can be directly deaminated?

A

Glutamate

SMP - MNE Exam 2 (17 decks)

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