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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
Gluconeo Step 3?
Malate transport from mitosol to cytosol
26
Gluconeo Step 5: Reactant/Products? Include # of Cs.
Oxaloacetate (4C) + GTP => Phosphoenolpyruvate (3C) + GDP + CO2
27
Gluconeo Step 5: Reversible or irreversible?
Reversible
28
Where does gluconeo step 5 happen?
Can happen either in mitosol or cytosol
29
Gluconeo Step 5: Enzyme?
Cytosolic/Mitochondrial PEP carboxykinase
30
Gluconeo Step 5: Cofactor?
GTP
31
Where is PEPCK present?
1. Liver 2. Kidneys 3. Adipocytes 4. Muscles
32
Where is pyruvate carboxylase found?
1. Liver 2. Kidneys 3. Adipocytes
33
What is the purpose of having PEPCK in muscles? When is this most useful?
Performs reverse reaction as a key anaplerotic reaction which is key in muscles during high physical activity during which energy is needed
34
What happens after mitochondrial PEPCK converts oxaloacetate to PEP? In which cases does this happen?
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
35
Gluconeo Step 6: Enzyme?
Enolase
36
Gluconeo Step 6: Reactant/Products? Include # of Cs.
Phosphoenolpyruvate (3C) + H2O => 2-phosphoglycerate (3C)
37
Gluconeo Step 7: Enzyme?
Phosphoglycerate mutase
38
Gluconeo Step 7: Reactant/Products? Include # of Cs.
2-phosphoglycerate (3C) => 3-phosphoglycerate (3C)
39
Gluconeo Step 8: Enzyme?
Phosphoglycerate kinase
40
Gluconeo Step 8: Reactant/Products? Include # of Cs.
3-phosphoglycerate (3C) + ATP => 1,3BPG (3C) + ADP
41
Gluconeo Step 9: Enzyme?
Glyceraldehyde-3-Phosphate Dehydrogenase (GAPDH)
42
Gluconeo Step 9: Reactant/Products? Include # of Cs.
1,3-bisphosphoglycerate (3C) + NADH + H+ => GAP (3C) + Pi + NAD+
43
Gluconeo Step 10: Enzyme?
TPI
44
Gluconeo Step 10: Reactant/Products? Include # of Cs.
DHAP (3C) => GAP (3C)
45
Gluconeo Step 11: Enzyme?
Aldolase
46
Gluconeo Step 11: Reactant/Products? Include # of Cs.
DHAP (3C) + GAP (3C) => F1,6BP (6C)
47
Gluconeo Step 12: Enzyme?
Fructose-1,6-bisphosphatase
48
Gluconeo Step 12: Reactant/Products? Include # of Cs.
F1,6BP (6C) => F6P (6C) + Pi
49
What is fructose-1,6-bisphosphatase stimulated by?
1. Absence of F26BP | 2. Glucagon/cAMP
50
What do we call F-2,6-BP in regards to its effect on fructose-1,6-bisphosphatase?
An allosteric effector
51
How are levels of F-2,6-BP downregulated?
Glucagon/epi activate PKA to phosphorylate Fructose-2 bisphosphatase (FBPase-2), activating it, which dephosphorylates F-2,6-BP
52
Explain how PFK2 is regulated when blood glucose is high?
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
Explain how PFK2 is regulated when blood glucose is low?
Glucagon phosphorylates PKA (active) --> PKA phosphorylates PFK2 (inactive) --> activating the FBPase2 --> dephosphorylates F-2,6-BP to F-6P --> PFK not activated
54
Gluconeo Step 13: Reactant/Products? Include # of Cs.
F6P (6C) => G6P (6C)
55
Gluconeo Step 13: Enzyme?
Phosphohexose isomerase
56
Gluconeo Step 14: Reactant/Products? Include # of Cs.
G6P (6C) => Glucose (6C) + Pi
57
Gluconeo Step 14: Enzyme?
G6P phosphatase
58
Where does the NADH and ATP/GTP for gluconeo come from? What happens when this runs out?
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
AA catabolism Step 1: Reactant/Products?
AA + alpha-ketoglutarate => alpha keto acid + glutamate
60
How does starvation affect the rate of step 1 of AA catabolism? What is the purpose of this?
TCA cycle rate increased => less alpha-ketoglutarate available to accept amino group => lower rate of AA catabolism Purpose: avoid muscle wasting during starvation
61
AA catabolism Step 1: Enzyme?
Aminotransferase
62
AA catabolism Step 1: Cofactor? Role?
Pyridoxal phosphate (PLP) (VB6 derivative): conduit to accept amino group
63
What is the precursor to pyridoxal phosphate?
Vitamin B6
64
AA catabolism Step 2: Reactant/Products?
Glutamate + H2O + NADP/NAD+ => alpha-ketoglutarate + NADPH/NADH + NH4+
65
AA catabolism Step 2: Enzyme?
Glutamate dehydrogenase
66
Gluconeo Step 2: Enzyme?
Malate dehydrogenase
67
Gluconeo Step 4: Enzyme?
Malate dehydrogenase
68
Other than glutamate, what is another good nitrogen donor? Describe the reaction. Where is this enzyme found?
Glutaminase: glutamine + H2O => glutamate + NH4+ | Liver and kidney
69
Which steps of gluconeo happen in the mitochondria?
1 and 2 | Optional: 4 and 5
70
Why else is malate transport from mitosol to the cytosol important (other than transporting oxaloacetate out)?
It transports NADH out which is needed for gluconeo!
71
Under what conditions do steps 4 and 5 of gluconeo happen in the mitosol?
When the pyruvate source is lactate because NADH has already been generated in the cytosol by lactate dehydrogenase
72
Where is the enzyme glucose-6-phosphatase found in the liver cells?
The ER
73
What is the deamination of AAs limited by? Purpose of this?
The availability of alpha-ketoglutarate, which is a TCA intermediate Starvation: low TCA intermediates so slows down AA degradation: PREVENTS MUSCLE WASTING
74
AA catabolism Step 2: Cofactor?
NADP OR NAD+ (rare enzyme that can use both)
75
AA catabolism Step 1: Reactant/Products?
Amino acid + alpha-ketoglutarate => alpha-keto acid + glutamate
76
Can FAs be used for gluconeogenesis?
Odd numbered ones can because propionyl-CoA converted to succinyl-CoA
77
Where does AA catabolism happen?
Mitosol
78
What are the 2 types of malate dehydrogenases and what are they used for?
1. Mitochondrial: TCA cycle AND gluconeogenesis (oxaloacetate to malate) 2. Cytosolic: gluconeogenesis
79
Where does the conversion of oxaloacetate to malate happen?
Mitochondria
80
Where does the conversion of malate to oxaloacetate happen?
Both cytosol and mitosol
81
What is the exact definition of a cofactor?
Substance (other than the substrate) whose presence is essential for the activity of an enzyme
82
What is fructose-1,6-bisphosphatase inhibited by?
1. AMP | 2. High levels of fructose-2,6-BP
83
What is the major source for gluconeo during the fasting state?
AAs
84
When is glycerol used in gluconeo?
Starvation
85
What is the main anaplerotic enzyme in the kidney?
Pyruvate carboxylase
86
Which is the only AA that can be directly deaminated?
Glutamate

SMP - MNE Exam 2 (17 decks)

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