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Biochem Take 2. > Gluconeogenesis. > Flashcards

Gluconeogenesis. Flashcards

1
Q

What is allosteric activation?

A

When an enzyme is activated by the binding of a molecule to its allosteric site.

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2
Q

What is an allosteric site?

A

A site on an enzyme that is distinct from the binding site.

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3
Q

What happens when a molecule binds to the allosteric site?

A

It may activate or inhibit the enzyme.

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4
Q

What is an apoenzyme?

A

An enzyme that is in its inactive state.

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5
Q

What is a co-enzyme?

A

An organic molecule that is not a protein and will bind to an enzyme to help it perform its task.

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6
Q

What is the overall aim of the gluconeogenesis pathway?

A

To produce new molecules of glucose from smaller molecules.

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7
Q

Will gluconeogenesis function in the well fed state or the fasting state?

A

In the fasting state.

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8
Q

Gluconeogenesis is a reverse of what other pathway?

A

Glycolysis.

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9
Q

Which steps of glycolysis can gluconeogenesis not reverse?

A

The irreversible rate limiting steps.

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10
Q

What steps of gluconeogenesis are the reverse of steps from glycolysis?

A

The reversible steps.

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11
Q

How long after a meal does it take for gluconeogenesis to start?

A

Around 5 hours.

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12
Q

What would happen if gluconeogenesis did not occur?

A

Blood sugar levels would drop and the organs are solely dependent on glucose for their energy would stop functioning.

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13
Q

Name some organs that are dependent on glucose for their energy?

A

Brain.

Erythrocytes.

Testes.

Kidney medulla.

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14
Q

Gluconeogenesis will help to balance the levels of what in the body?

A

Blood glucose levels.

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15
Q

Without gluconeogenesis occurring, would a person become hyperglycaemic or hypoglycaemic?

A

Hypoglycaemic.

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16
Q

What is used to keep blood sugar levels balanced while gluconeogenesis gets going?

A

Glycogen stores.

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17
Q

What are the 3 pre-cursor molecules that are used for gluconeogenesis?

A

α-keto acids.
Glycerol.
Lactate and pyruvate.

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18
Q

Where are the α-keto acids used as a pre-cursor for gluconeogenesis made?

A

From amino acid metabolism.

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19
Q

Where is the glycerol used as a pre-cursor for gluconeogenesis made?

A

From lipids.

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20
Q

In what organs will gluconeogenesis occur?

A

90% in the liver.

10% will occur in the kidneys

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21
Q

Will gluconeogenesis occur in all cells?

A

No.

Only in the liver and kidney cells.

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22
Q

How does gluconeogenesis get around the 3 irreversible steps of glycolysis?

A

It will bypass them.

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23
Q

Where does the 1st step of gluconeogenesis occur?

A

In the cytoplasm and mitochondrial matrix.

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24
Q

What happens in part 1 of the 1st step of gluconeogenesis?

A

2 pyruvate into the mitochondrial matrix where they are converted to oxaloacetate.

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25
Q

Where do the 2 pyruvate molecules that are transported into the mitochondrial matrix come from?

A

They come from the cytoplasm.

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26
Q

What enzyme converts the 2 pyruvate molecules to oxaloacetate in step 1 part 1?

A

Pyruvate carboxylase.

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27
Q

How does pyruvate carboxylase convert the 2 pyruvate molecules in step 1 part 1?

A

It adds a CO2 molecule to each pyruvate to form oxaloacetate.

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28
Q

Will pyruvate ever leave the cell?

A

No.

So, it will never be found in the bloodstream.

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29
Q

Where will the enzyme, pyruvate carboxylase be found?

A

Only in the liver and the kidneys.

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30
Q

Does pyruvate carboxylase require any co-enzymes?

A

Yes.

Biotin.

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31
Q

Is any energy used up in step 1 part 1 of gluconeogenesis where pyruvate is converted to oxaloacetate?

A

1 ATP.

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32
Q

How many pyruvates are produced per glucose molecule?

A

2.

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33
Q

Is step 1 of gluconeogenesis a reverse of the final step of glycolysis?

A

No.

Step 9 of glycolysis is irreversible so step 1 of gluconeogenesis must bypass it.

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34
Q

What happens in part 2 of step 1 of gluconeogenesis?

A

Oxaloacetate is converted to malate.

Malate crosses into the cytoplasm and is re-oxidised to form oxaloacetate and NADH.

Oxaloacetate is then converted to phosphoenol pyruvate.

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35
Q

Why is oxaloacetate converted to malate in part 2 of step 1 of gluconeogenesis?

A

Because oxaloacetate cannot cross the mitochondrial membrane

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36
Q

What enzyme converts oxaloacetate to malate?

A

Malate dehydrogenase.

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37
Q

Is any energy used in part 2 of step 1 of gluconeogenesis?

A

1 GTP.

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38
Q

How much total energy is used up per pyruvate molecule in step 1 of gluconeogenesis?

A

1 ATP.

1 GTP.

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39
Q

Is any energy generated in part 2 of step 1 of gluconeogenesis?

A

1 NADH.

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40
Q

How much energy is gained in step 1 of gluconeogenesis?

A

1 NADH.

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41
Q

What is the net spend of energy in step 1 of gluconeogenesis?

A

1 ATP.

1 GTP.

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42
Q

Can Phosphoenol pyruvate (PEP) be converted to fructose 1,6-bisphosphate by reversing glycolysis?

A

Yes.

All of the steps back to step 3 of glycolysis (7 of gluconeogenesis) are reversible.

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43
Q

Is step 7 of gluconeogenesis a reverse of step 3 of glycolysis?

A

No.

Step 3 of glycolysis is irreversible.

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44
Q

What location do steps 2-9 occur in gluconeogenesis?

A

In the cytoplasm.

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45
Q

What happens in step 7 of gluconeogenesis?

A

The phosphate group on carbon 1 is removed from the molecule to form fructose 6-phosphate.

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46
Q

What enzyme de-phosphorylates carbon 1 of fructose-1,6 bisphosphate in step 7 of gluconeogenesis?

A

Fructose 1,6-bisphosphatase.

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47
Q

The bi-functional enzyme that is used in step 3 of glycolysis and step 7 of gluconeogenesis is made up of what 2 enzymes?

A

Fructose 2,6-bisphosphatase (F 2,6 BPase).

Phosphofructokinase-2 (PFK-2).

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48
Q

Is step 8 of gluconeogenesis a reverse of step 2 of glycolysis?

A

Yes.

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49
Q

Where does step 9 of gluconeogenesis occur?

A

In the ER of the liver and in the cytoplasm.

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50
Q

What happens in step 9 of gluconeogenesis?

A

The phosphate group will be removed from carbon 6 of glucose 6-phosphate.

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51
Q

Is step 1 of glycolysis reversible?

A

No.

To form glucose, gluconeogenesis must bypass step 1 of glycolysis.

52
Q

Where does the de-phosphorylation of glucose-6 phosphate occur?

A

In the ER of liver and kidney cells.

53
Q

Can glucose 6-phosphate be released into the bloodstream?

A

No.

It must be converted to glucose 1st.

54
Q

What transporter will release glucose into the bloodstream at the end of gluconeogenesis?

A

GLUT-2.

55
Q

What transporter will take glucose between the cytoplasm and the ER of the liver of kidneys?

A

GLUT-7.

56
Q

What enzyme will remove the phosphate group from glucose 6-phosphate in step 9 of gluconeogenesis?

A

Glucose 6-phosphatase.

57
Q

Where can glucose 6-phosphatase be found?

A

In the endoplasmic-reticulum of kidney and liver cells.

58
Q

In what steps of gluconeogenesis are ATP molecules used for energy?

A

Step 4.

Step 1.

59
Q

How many ATP molecules are used in step 4 and step 1 of gluconeogenesis?

A

1 ATP per pyruvate.

2 ATP per glucose.

60
Q

How much energy is used in gluconeogenesis to form a glucose molecule?

A

4 ATP molecules.

2 GTP molecules.

2 NADH molecules.

61
Q

In total, how many ATPs are used up in gluconeogenesis?

A

12 ATP.

62
Q

What are the regulated enzymes in gluconeogenesis and what steps are they used in?

A

Pyruvate carboxylase. (Step 1, part 1).

PEP carboxykinase. (Step 1, part 2).

Fructose 1,6-bisphosphatase. (Step 7).

63
Q

What is pyruvate carboxylase activated by?

A

ACoA (allosterically).

64
Q

Where will the ACoA that is used to activate pyruvate carboxylase be made?

A

By fatty acid oxidation.

65
Q

What is fatty acid oxidation?

A

An additional energy source that can be used when glucose levels are low.

66
Q

If the levels of ACoA in the liver increase, what will happen?

A

Pyruvate carboxylase will be stimulated.

67
Q

What is pyruvate carboxylase inhibited by?

A

ADP.

68
Q

What is PEP carboxykinase activated by?

A

Glucagon and ADP.

69
Q

What is pyruvate carboxylase inhibited by?

A

ADP.

70
Q

What hormone will cause an up-regulation of PEP carboxykinase?

A

Glucagon.

71
Q

What is fructose 1,6-bisphosphatase activated by?

A

High levels of ATP.

Low levels of AMP.

72
Q

What is fructose 1,6-bisphosphatase inhibited by?

A

Fructose 2,6 bisphosphate.

Low levels of ATP.

73
Q

What type of activation does fructose 1,6-bisphosphatase have?

A

Allosteric and hormonal.

74
Q

What type of inhibition does fructose 1,6-bisphosphatase have?

A

Allosteric.

75
Q

Biotin is what form of co-enzyme?

A

A vitamin.

76
Q

How does biotin help pyruvate carboxylase?

A

Biotin helps to transfer CO2 to pyruvate forming oxaloacetate.

77
Q

What must be removed from the cell to allow fructose 1,6 bisphosphatase to work?

A

Fructose 2,6 bisphosphate.

78
Q

Fructose 2,6 bisphosphate will activate what metabolic pathway?

A

Glycolysis.

79
Q

Fructose 2,6 bisphosphate will inhibit what metabolic pathway?

A

Gluconeogenesis.

80
Q

What enzyme will remove fructose 2,6 bisphosphate from the cell to allow gluconeogenesis to occur?

A

Fructose bisphosphatase-2.

81
Q

What is fructose bisphosphatase-2 activated by?

A

Phosphorylation.

82
Q

What pathway will activate the phosphorylation of FBPase-2?

A

PKA via the cAMP pathway which is activated by glucagon.

83
Q

Does the phosphorylation of FBPase-2 use up any energy?

A

1 ATP.

84
Q

What will FBPase-2 do once it is activated?

A

FBPase-2 will start to break down F 2,6-BP, removing it from the cell.

85
Q

What happens once F2,6-BP can be removed from the cell?

A

F,1,6-BPase can form fructose 6 phosphate and gluconeogenesis to continue.

86
Q

Is F2,6-BP made in gluconeogenesis or glycolysis?

A

No.

It is made via a side pathway.

87
Q

What happens when the bi-functional enzyme is phosphorylated?

A

FBPase-2 will be inactive.

PFK-2 will be active.

88
Q

What will lead to the phosphorylation of the bi-functional enzyme?

A

Insulin via the CAMP pathway.

89
Q

What stimulates the synthesis of F 2,6-BP?

A

PFK-2.

90
Q

What hormone stimulates gluconeogenesis?

A

Glucagon.

91
Q

How will a rise in glucagon affect levels of fructose 2,6-bisphosphate?

A

It will lower them.

92
Q

How does glucagon lower levels of fructose 2,6-bisphosphate?

A

Glucagon will activate the cAMP pathway which will phosphorylate the bi-functional enzyme allowing FBPase-2 to break down F 2,6-BP.

93
Q

What does the break down of F 2,6-BP allow fructose 1,6 BPase to do?

A

To convert glucose 6-phosphate to glucose.

94
Q

How will glucagon affect pyruvate kinase?

A

Glucagon activates the cAMP pathway and phosphorylates pyruvate kinase.

95
Q

What stimulates the release of glucagon?

A

Low blood sugar.

96
Q

Is pyruvate kinase inhibited when it is phosphorylated or when it is de-phosphorylated?

A

When it is phosphorylated.

97
Q

The inhibition of pyruvate kinase results in the activation of what metabolic pathway?

A

Gluconeogenesis.

98
Q

Will a rise in glucagon affect any the concentration of any allosteric effectors of glycolysis or gluconeogenesis?

A

It will lower levels of fructose 2,6-bisphosphate.

99
Q

What will affect the rate of gluconeogenesis?

A

The availability of guconeogenic pre-cursors.

100
Q

The availability of what gluconeogenic pre-cursor will result particularly affect the rate of gluconeogenesis?

A

Glucogenic amino acids such as keto acids.

101
Q

Amino acids provide what for gluconeogenesis?

A

Carbon skeletons.

102
Q

What amino acid is the most favoured precursor for gluconeogenesis?

A

Alanine.

103
Q

What will activate hepatic pyruvate carboxylase during periods of starvation?

A

Acetyl CoA.

104
Q

How is ACoA formed?

A

Via the beta-oxidation of these fatty acids.

105
Q

Why is it important for ACoA levels to accumulate?

A

The accumulation of ACoA will stimulate pyruvate carboxylase to start gluconeogenesis.

106
Q

The pre-cursors for gluconeogenesis are intermediates from what forms of metabolism

A

Protein and lipid metabolism?

107
Q

How is glycerol produced?

A

Via the breakdown of fats during fasting.

108
Q

What specific form lf fat is hydrolised to form glycerol?

A

Triacylglycerols.

109
Q

What happens to the glycerol that is released from the oxidation of triacylglycerols?

A

It is delivered to the liver by the blood.

110
Q

What happens to glycerol when it is delivered to the liver?

A

It will be phosphorylated to form DHAP.

111
Q

What enzyme converts glycerol to DHAP?

A

Glycerol kinase.

112
Q

Can DHAP enter gluconeogenesis?

A

Yes.

113
Q

When is lactate released into the bloodstream?

A

By anaerobic glycolysis.

114
Q

What cycle converts lactate to pyruvate?

A

The CORI cycle.

115
Q

What happens in the CORI cycle?

A

Lactate will be picked up from the blood by the liver and will be converted to pyruvate.

116
Q

What enzyme converts lactate to pyruvate?

A

Lactate dehydrogenase.

117
Q

How can alanine be derived as a gluconeogenic pre-cursor?

A

From the natural degradation of muscle proteins.

118
Q

What happens to the amino acids muscle proteins once they are degraded?

A

They are released into the blood and delivered to the liver.

119
Q

What happens to the amino acids that are used for gluconeogenic pre-cursors once they enter the liver?

A

The keto-acids from alanine can be converted to pyruvate.

120
Q

What is the conversion of alanine to pyruvate known as?

A

The alanine - pyruvate cycle.

121
Q

What will happen to a person that has a heritable disease that results in a deficiency of glucose 6-phosphatase?

A

Glucose 6-phosphate cannot be converted to glucose.

This results in no release of glucose into the bloodstream.

122
Q

What is the disease called when there is a deficiency in glucose 6-phosphatase?

A

Von Gierkes disease.

123
Q

How will Von Gierkes disease affect an individual?

A

People who have this disease will become severely hypoglycaemic in the fasting state.

124
Q

What are the glycolytic and gluconeogenic rate limiting enzymes in step 9 of glycolysis

A

Glycolysis. Pyruvate kinase.

Gluconeogenesis. Pyruvate carboxylase and PEP CK.

125
Q

What are the glycolytic and gluconeogenic rate limiting enzymes in step 3 of glycolysis

A

Glycolysis. PFK-1.

Gluconeogenesis. Fructose 1,6-BPase.

126
Q

What are the glycolytic and gluconeogenic rate limiting enzymes in step 1 of glycolysis

A

Glycolysis. Hexokinase and glucokinase.

Gluconeogenesis. Glucose 6-phosphatase.

Biochem Take 2. (24 decks)

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