Gluconeogenesis Flashcards

1
Q

What is Gluconeogenesis?

A

It is the process by which glucose is derived from pyruvate

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2
Q

Where is the major site of gluconeogenesis?

A

The major site of gluconeogenesis is the liver (Can also occur in the kidney)

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3
Q

When is gluconeogenesis important?

A

Gluconeogenesis is especially important during
fasting or starvation

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4
Q

What are the steps of gluconeogenesis? (exclusive steps only)

A
  1. Pyruvate into oxaloacetate
  2. Oxaloacetate into phosphoenolpyruvate
    3-8. Reversed glycolysis steps using the same enzymes
  3. Fructose 1,6-bisphosphatase to Fructose 6-phosphatase (Using a new enzyme)
  4. Reversed glycolysis steps using the same enzymes
  5. Glucose 6-phosphate into glucose (Using a new enzyme)
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5
Q

Which enzymes are found in gluconeogenesis but not in glycolysis.

A
  1. Pyruvate Carboxylase
  2. Phosphoenolpyruvate Carboxykinase
  3. Fructose 1,6-bisphosphatase
  4. Glucose-6-Phosphatase
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6
Q

What are the two types of gluconeogenesis vs glycolysis regulation?

A

Reciprocal Regulation: When one pathway is active the other is inhibited
Positive Effectors for Glycolysis (AMP, F-2,6-BP, F-1,6-BP) Negative effectors for Glycolysis (ATP, Alanine, Citrate, H+, G6P)
Positive Effectors for Gluconeogenesis (Citrate, Acetyl-CoA)
Negative effectors for Gluconeogenesis (ADP, AMP, F-2,6-BP)

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7
Q

What are the three key enzymes for gluconeogenesis?

A
  1. Pyruvate carboxylase
  2. FBPase
  3. Glucose-6-phosphatase
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8
Q

What is the key regulator of glucose metabolism in the liver?

A

Fructose 2,6-bisphosphate (Stimulates phosphofructokinase and inhibits fructose 1,6-bisphosphatase)

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9
Q

What is the pathway that occurs when blood glucose levels are low?

A
  1. Glucagon is released
  2. Phosphorylation of the PFK2-FPBase2 enzyme
  3. Deactivation of the kinase domain and activation of the phosphate domain
  4. Lowering the amount of F-2,6-BP in the cell
  5. Glycolysis would slow down and Gluconeogenesis would speed up
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10
Q

What is the pathway that occurs when blood glucose levels are high?

A
  1. Insulin is released
  2. Dephosphorylation of the PFK2-FPBase2 enzyme
  3. Activation of the kinase domain and deactivation of the phosphate domain
  4. Raising the amount of F-2,6-BP in the cell
  5. Glycolysis would speed up and Gluconeogenesis would slow down
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11
Q

Why is the reaction catalyzed by the pyruvate dehydrogenase complex a crucial juncture in metabolism?

A

The pyruvate dehydrogenase complex converts pyruvate into acetyl-CoA, which enters the TCA cycle. (This bridges Glycolysis and the Citric Acid Cycle)

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12
Q

Which enzymes make up the pyruvate dehydrogenase complex? What does each one do?

A

Pyruvate Dehydrogenase (E1): removes a carbon from pyruvate
Dihydrolipoamide Acetyltransferase (E2): forms acetyl-CoA
Dihydrolipoamide Dehydrogenase (E3): restores the lipoamide cofactor of E2

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13
Q

What are the cofactors for the enzymes that make up the pyruvate dehydrogenase complex?

A

Pyruvate Dehydrogenase (E1): Thiamine (Vitamin B1) (TPP)
Dihydrolipoamide Acetyltransferase (E2): Lipoic acid & Coenzyme A (CoA)
Dihydrolipoamide Dehydrogenase (E3): FAD & NAD⁺

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14
Q

What is each cofactor responsible for in the pyruvate dehydrogenase complex?

A

TPP: Works with E1 to help remove a carbon from pyruvate
Lipoamide: Carries the intermediate product from E1 to E2
CoA: Joins with the intermediate from E2 to form acetyl-CoA
FAD: Helps in E3 to transfer electrons
NAD+: Picks up electrons in the final step to make NADH

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15
Q

How is the Pyruvate Dehydrogenase Complex regulated?

A

Allosteric Regulation: High levels of acetyl-CoA, NADH, and ATP inhibit the activity of the PDC, increased levels of ADP and pyruvate can activate PDC
Covalent modification: Deactivated when phosphorylated,
activated when not phosphorylated

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16
Q

What is the purpose of the citric acid cycle?

A

The primary catabolic function of the citric acid cycle is to generate high-energy electron carriers (NADH and FADH₂) and GTP/ATP by oxidizing acetyl-CoA.

17
Q

How is the citric acid cycle regulated?

A

Allosteric Regulation: Isocitrate dehydrogenase is activated by ADP and inhibited by ATP and NADH
Substrate Availability: Levels of acetyl-CoA, NAD⁺, and oxaloacetate impact the cycle’s rate.
Feedback Inhibition: High concentrations of the products ATP and NADH inhibit early enzymes in the cycle

18
Q

What is the role of the Citric Acid Cycle in Anabolism?

A

Lots of the intermediate products can be used as building blocks for other things like proteins, lipids, and DNA

19
Q

What are the steps of the citric acid cycle?

A
  1. Acetyl-CoA + Oxaloacetate → Citrate
  2. Citrate → Isocitrate
  3. Isocitrate → α-Ketoglutarate + CO₂ + NADH
  4. α-Ketoglutarate → Succinyl-CoA + CO₂ + NADH
  5. Succinyl-CoA → Succinate + GTP
  6. Succinate → Fumarate + FADH₂
  7. Fumarate → Malate
  8. Malate → Oxaloacetate + NADH
20
Q

What are the products of each citric acid cycle?

A

Each cycle turn produces 3 NADH, 1 FADH₂, and 1 GTP (or ATP), and releases two molecules of CO₂.

21
Q

What mnemonic helps you easily remember the STEPS/PRODUCTS of the citric acid cycle?

A

“Can I Keep Selling Substances For Money, Officer?”
C (Citrate)
I (Isocitrate)
K (α-Ketoglutarate)
S (Succinyl-CoA)
S (Succinate)
F (Fumarate)
M (Malate)
O (Oxaloacetate)

22
Q

Which steps of the citric acid cycle produce NADH?

A

Step 3. Isocitrate → α-Ketoglutarate + CO₂ + NADH

Step 4. α-Ketoglutarate → Succinyl-CoA + CO₂ + NADH

Step 8. Malate → Oxaloacetate + NADH

23
Q

Which step of the citric acid cycle produces FADH₂?

A
  1. Succinate → Fumarate + FADH₂
24
Q

Which steps of the citric acid cycle produce CO₂?

A
  1. Isocitrate → α-Ketoglutarate + CO₂ + NADH
  2. α-Ketoglutarate → Succinyl-CoA + CO₂ + NADH
25
Q

Which step of the citric acid cycle produces GTP?

A
  1. Succinyl-CoA → Succinate + GTP
26
Q

What are the regulatory enzymes of the citric acid cycle?

A

Isocitrate Dehydrogenase (Rate limiting)
Alpha-Ketogluterase Dehydrogenase

27
Q

What are all the enzymes of the citric acid cycle?

A
  1. Citrate synthase
  2. Aconitase
  3. Isocitrate dehydrogenase
  4. alpha-ketoglutarate dehydrogenase
  5. Succinyl-CoA synthetase
  6. Succinate dehydrogenase
  7. Fumarase
  8. Malate dehydrogenase
28
Q

What mnemonic helps you easily remember the ENZYMES of the citric acid cycle?

A

“Cindy And I Knew Some Silly Fun Magic”