Chapter 28 Gluconeogenesis Flashcards

1
Q

List the precursors of gluconeogenesis and where they come from

A
  1. lactate: anaerobic glycolysis (RBC & muscle)
  2. glycerol: released from adipose stores of triacylglycerol
  3. amino acids: especially alanine, from degradation of muscle protein
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2
Q

What makes the carbons of glycerol gluconeogenic?

A

They form dihydroxyacetone phosphate (DHAP), a glycolytic intermediate.

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3
Q

Is gluconeogenesis the reverse of glycolysis? Why or why not?

A

Glycolysis has three highly exergonic steps, so gluconeogenesis must use other enzymes to make glucose from pyruvate. Thus, gluconeogenesis is not the exact opposite of glycolysis.

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4
Q

How is the conversion of pyruvate to phosphoenolpyruvate regulated?

A

Pyruvate carboxylase is activated by acetyl CoA. PEPCK is induced (transcription and translation increased) by cAMP induced by glucagon (fasting) or by epinephrine (stress). CREB (cAMP response element binding protein) activates transcription. When glucagon is elevated, liver pyruvate kinase is phosphorylated (involving PKA from GPCR cascade). This prevents PEP from reconversion to pyruvate, and avoids a futile cycle. PKA phosphorylates and activates phosphorylase kinase, and phosphorylates and INactivates glycogen syntase. Phosphorylase kinase activates phosphorylase, which breaks down glycogen.

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5
Q

What is the primary source of glucose at the 12 hour mark of a fast?

A

glycogenolysis

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6
Q

What 2 tissues cannot synthesize their own glucose but depend on glucose for energy?

A

the brain and RBCs

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7
Q

Where does lactate come from?

A

Primarily RBCs, and some from muscles during exercise

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8
Q

When is the CO2 that was added to pyruvate to form oxaloacetatereleased?

A

In the reaction catalyzed by phosphoenolpyruvate carboxykinase.

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9
Q

What 3 sequences in gluconeogenesis are regulated?

A
  1. pyruvate –> PEP
  2. Fructose 1,6-bisP –> fructose 6-P
  3. Glucose 6-P –> glucose
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10
Q

When will PEP form glucose and NOT pyruvate?

A

When pyruvate dehydrogenase is inactive (phosphorylated and therefore, not converted to acetyl CoA), pyruvate carboxylase is active, PEP carboxykinase is induced, and/or pyruvate kinase is inactive.

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11
Q

What is the key difference of glucose between liver and muscle?

A

Insulin is greatly stimulates transport of glucose into muscle cells, BUT only slightly simulates the transport of glucose into liver cells.

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12
Q

What can deliver triglycerides to muscle for immediate oxidation if energy is required?

A

VLDL

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13
Q

How do glucagon blood levels respond to a high-carb meal and to a high-protein meal?

A

Glucagon blood levels DECREASE in response to a high-carb meal and INCREASE in response to a high-protein meal.

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14
Q

What type of meal keeps glucagon blood levels constant and allow insulin levels to increase?

A

A mixed meal containing carb, protein, and fat

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15
Q

When is the glycolytic enzyme, pyruvate kinase, activated and inhibited? When it is inhibited, what pathway would its inhibition help begin?

A

Pyruvate kinase is activated by fructose-1,6-bisphosphate and is inhibited by ATP and alanine and is inhibited by phosphorylation (glucagon and epinephrine lead to an increase in cAMP levels, which activates protein kinase A).
Pyruvate kinase inhibition contributes to the activation of gluconeogenesis.

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16
Q

When is the glycolytic enzyme, phosphofructokinase-1, activated and inhibited? Its inhibition contributes to the stimulation of what pathway?

A

Phosphofructokinase-1 is activated by fructose-2,6-bisphosphate and AMP and is inhibited by ATP and citrate. Its inhibition contributes to the stimulation of gluconeogenesis.

17
Q

What is the glycolytic enzyme’s, glucokinase, mechanism? What happens when its inhibited?

A

Glucokinase has a high Km for glucose and is induced by insulin. When [insulin] is low like in the fasting state, glucokinase is inhibited, allowing gluconeogenesis to be stimulated.

18
Q

When is pyruvate carboxylase activated in gluconeogenesis?

A

Activated by acetyl-CoA

19
Q

When is phosphoenolpyruvate carboxy kinase (PEPCK) induced and repressed?

A

Induced (increase in gene transcription) by glucagon, epinephrine, or glucocorticoids
Repressed (decrease in gene transcription) by insulin

20
Q

When is glucose 6-phosphatase induced?

A

Its induced (increase in gene transcription) during fasting

21
Q

When is fructose 1, 6-bisphosphatase induced and inhibited?

A

Induced (increase in gene transcription) during fasting

22
Q

What determines the relative activity or amount of the glycolytic or gluconeogenic enzymes?

A

The net flow of carbons

Glycolysis: Glucose to Pyruvate
Gluconeogenesis: Pyruvate to Glucose