Chapter 17: Gluconeogenesis Flashcards

1
Q

Where are the major sites of gluconeogenesis?

A

Liver and kidneys

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2
Q

Gluconeogenesis is important for maintaining ________ during _____.

A

Normal blood glucose levels during starvation

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3
Q

Brain uses only glucose, therefore the liver essentially works to…

A

Make the brain happy by maintaing blood glucose levels

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4
Q

Most of the glucose generated in gluconeogenesis is used by _____ and ______.

A

Brain and contracting muscle

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5
Q

Gluconeogenesis converts ______ to ______.

A

Pyruvate to Glucose

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6
Q

What are the three precursors for gluconeogenesis?

A
  1. Lactate (muscle)
  2. Amino acids
  3. Glycerol (adipose tissue)

Not present in glycolysis

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7
Q

Glycerol enters gluconeogenesis as…

A

Dihydroxyacetone phosphate

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8
Q

The 3 irreversible reactions of glycolysis are…

A

Bypassed in gluconeogenesis by new steps/enzymes

7/10 Enzymes are the same

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9
Q

Pyruvate kinase reaction (irreversible) of glycolysis is bypassed by:

A
  • Pyruvate carboxylase
  • Phosphoenolpyruvate carboxykinase (PEP)
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10
Q

Step 1 of gluconeogenesis

A

Pyruvate carboxylated to oxaloacetate by pyruvate carboxylase (mitochondrial enzyme)

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11
Q

First step of gluconeogenesis occurs in the…

A

Mitochondrial matrix

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12
Q

Oxaloacetate is transported to the cytosol as…

A

Malate

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13
Q

Once reoxidized in the cytoplasm, oxaloacetate is decarboxylated and phosphorylated to…

A

PEP by PEP carboxykinase

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14
Q

In glycolysis, PFK controls the rate. What enzyme controls the rate of gluconeogenesis, bypassing the PFK reaction?

A

Fructose 1,6-bisphosphatase (FBPase)

*Allosteric enzyme that controls gluconeogenesis

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15
Q

Which enzyme is critical for free glucose levels?

A

Glucose 6-phosphatase

*Reverse of hexokinase

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16
Q

Free glucose is generated mainly in the…

A

Liver

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17
Q

Glucose 6-phosphatase is present only in…

A

Liver and kidney

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18
Q

Glucose 6-phosphate is hydrolyzed to ______ in the _______.

A

Glucose in the ER lumen

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19
Q

When glucose is abundant, which process will predominate?

A

Glycolysis

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20
Q

When glucose is scarce, which process will take over?

A

Gluconeogenesis

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21
Q

Both glycolysis and gluconeogenesis are highly _____ under cellular conditions.

A

Exergonic

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22
Q

When synthesizing glucose from pyruvate, __________ are spent.

A

6 high transfer-potential phosphoryl transfer groups (4 ATP and 2 GTP)

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23
Q

What is lactic acidosis?

A

Accumulation of lactic acid in the blood (lowers the pH) which is caused by a deficiency in gluconeogenic enzymes

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24
Q

What is hypoglycemia?

A

Low blood glucose levels

-Liver cannot produce glucose to maintain normal glucose levels

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25
Q

Gluconeogenesis and glycolysis are…

A

Coordinated

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26
Q

Rate of glycolysis is determined by…

A

Glucose concentration

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27
Q

Rate of gluconeogenesis is dependent on…

A

Lactate concentration and other precursors

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28
Q

When high levels of AMP…

A

Low energy

Glycolysis turned on

Gluconeogenesis turned off

(AMP stimulates PFK, but inhibits Fructose 1,6-bisphosphatase)

29
Q

When high levels of ATP…

A

High energy

Turn off glycolysis

(Citrate inhibits PFK)

30
Q

Citrate is an activator of ________ and promotes ________.

A

Fructose 1,6-bisphosphatase and promotes gluconeogenesis

31
Q

Pyruvate carboxylase - what activates/inhibits?

A

Activated by ADP

Inhibited by acetyl CoA

32
Q

PEP carboxykinase is inhibited by…

A

ADP

33
Q

If ATP is required, ________ predominates.

A

Glycolysis

34
Q

If glucose is required, ________ is favored.

A

Gluconeogenesis

35
Q

Blood glucose levels regulate glycolysis and gluconeogenesis in _____ by changing _______.

A

Liver

Fructose 2,6-bisphosphate levels

36
Q

Fructose 2,6-bisphosphatase is an ________ and stimulates _______. Also inhibits __________.

A

Allosteric regulator

Stimulates PFK

Inhibits Fructose1,6-bisphosphatase

37
Q

At high blood glucose levels, fructose 2,6-bisphosphate levels _____.

A

Increase

38
Q

When blood glucose levels are low, fructose 2,6-bisphosphate is converted to…

A

Fructose 6-phosphate

39
Q

PFK2 and FBPase2 are present in a single polypeptide chain. This is a ________ enzyme with three domains. What are they?

A

Bifunctional enzyme

Domains: N-terminal regulatory, kinase and phosphatase

40
Q

PFK2 and FBPase2 are controlled ________ by ________ of a single serine residue.

A

Reciprocally by phosphorylation

41
Q

Phosphorylation activates _____ and inhibits _____ to turn off _______.

A

FBPase 2 activated

PFK2 inhibited

Turns off glycolysis

42
Q

When glucose is scarce, _______ levels rise in the blood and trigger a cascade of _______ to activate ____.

Which process is active? (Glycolysis/Gluconeogenesis)

A

Glucagon levels rise, trigger cyclic AMP and activate PKA

Gluconeogenesis is active

43
Q

When glucose is abudant, the enzyme becomes dephosphorylated, which activates _______ and inhibits ________.

Which process is active? (Glycolysis/Gluconeogenesis)

A

Activates PFK2

Inhibits FBPase2

Glycolysis is active

44
Q

Insulin levels rise after each meal in response to __________. Insulin promotes _______.

A

Increasing blood glucose levels

Promotes glycolysis

45
Q

Glucagon levels rise during ______ when glucose is _____. This promotes…

A

Fasting when glucose is scarce

This promotes gluconeogenesis

46
Q

Insulin normally inhibits _______. In type 2 diabetes, insulin _________. This condition is called __________.

A

Inhibits gluconeogenesis

Insulin fails to do this in type 2 diabetes. This is called insulin resistance.

(Liver does not react to insulin, it just keeps making glucose, even if starving)

47
Q

What two factors enhance insulin sensitivity?

A

Exercise and diet

48
Q

What is the Cori cycle?

A

Lactate produced by muscle during contraction is released into the blood.

*Interrelationship between liver and muscle

Liver removes the lactate, converts to glucose via gluconeogenesis which is released into the blood and taken up by muscle.

49
Q

What are the 3 major factors that control glycolysis and gluconeogenesis?

A
  1. ATP levels
  2. Citrate
  3. Blood glucose levels
50
Q

Glycolysis:

  • Major control point
  • Fructose 2,6-bisphosphate
  • AMP
  • Citrate
  • Hormonal activation by
A
  • PFK
  • Activates
  • Activates
  • Inhibits
  • Insulin
51
Q

Gluconeogenesis:

  • Major control point
  • Fructose 2,6-bisphosphate
  • AMP
  • Citrate
  • Hormonal activation by
A
  • FBPase
  • Inhibits
  • Inhibits
  • Activates
  • Glucagon
52
Q

The hexokinase reaction of glycolysis is bypassed during gluconeogenesis by the enzyme:

A

Glucose 6-phosphatase

53
Q

Which of the following molecules is NOT a precursor for gluconeogenesis?

A

Acetyl CoA

54
Q

Which enzyme controls the rate of gluconeogenesis?

A

Fructose 1,6-bisphosphatase

55
Q

Deficiencies in enzymes specific for gluconeogenesis lead to:

A

Lactic acidosis and hypoglycemia

56
Q

When blood glucose levels are high, insulin activates _______ and stimulates _______.

A

Activates protein phosphatase-1; glycogen synthesis

57
Q

Which enzyme converts pyruvate to oxaloacetate in gluconeogenesis?

A

Pyruvate carboxylase

58
Q

Which compound is NOT a precursor for the synthesis of glucose by gluconeogenesis?

A

Acetyl CoA

59
Q

Which enzyme controls the rate of gluconeogenesis?

A

Fructose 1,6-biphosphatase

60
Q

Deficiencies in enzymes specific for gluconeogenesis lead to:

A

Lactic acidosis and hypoglycemia

61
Q

What type of glycosidic bond causes the branching of glycogen?

A

alpha 1,6-glycosidic bond

62
Q

Glycogen phosphorylase cleaves glycogen and produces:

A

Glucose 1-phosphate

63
Q

When blood glucose levels are high, insulin activates____________
and stimulates _______________.

A

Protein phosphatase-1; glycogen synthesis

64
Q

Which enzyme is specific for the gluconeogenesis pathway?

A

Phosphoenolpyruvate carboxykinase

65
Q

The enzyme _______________ controls the rate of gluconeogenesis and is allosterically inhibited by high levels of _______________.

A

Fructose 1,6-bisphosphatase; fructose 2,6-bisphosphate

66
Q

Glucagon ________________ glycogen degradation and signals the __________ state.

A

stimulates; fasted

67
Q

Which enzyme is NOT specific for gluconeogenesis?

A

Phosphoglycerate mutase

68
Q

. Gluconeogenesis occurs in the ____________ and is activated during ______________.

A

Liver; starvation