Gluconeogenesis. Flashcards
1
Q
What is allosteric activation?
A
When an enzyme is activated by the binding of a molecule to its allosteric site.
2
Q
What is an allosteric site?
A
A site on an enzyme that is distinct from the binding site.
3
Q
What happens when a molecule binds to the allosteric site?
A
It may activate or inhibit the enzyme.
4
Q
What is an apoenzyme?
A
An enzyme that is in its inactive state.
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.
6
Q
What is the overall aim of the gluconeogenesis pathway?
A
To produce new molecules of glucose from smaller molecules.
7
Q
Will gluconeogenesis function in the well fed state or the fasting state?
A
In the fasting state.
8
Q
Gluconeogenesis is a reverse of what other pathway?
A
Glycolysis.
9
Q
Which steps of glycolysis can gluconeogenesis not reverse?
A
The irreversible rate limiting steps.
10
Q
What steps of gluconeogenesis are the reverse of steps from glycolysis?
A
The reversible steps.
11
Q
How long after a meal does it take for gluconeogenesis to start?
A
Around 5 hours.
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.
13
Q
Name some organs that are dependent on glucose for their energy?
A
Brain.
Erythrocytes.
Testes.
Kidney medulla.
14
Q
Gluconeogenesis will help to balance the levels of what in the body?
A
Blood glucose levels.
15
Q
Without gluconeogenesis occurring, would a person become hyperglycaemic or hypoglycaemic?
A
Hypoglycaemic.
16
Q
What is used to keep blood sugar levels balanced while gluconeogenesis gets going?
A
Glycogen stores.
17
Q
What are the 3 pre-cursor molecules that are used for gluconeogenesis?
A
α-keto acids.
Glycerol.
Lactate and pyruvate.
18
Q
Where are the α-keto acids used as a pre-cursor for gluconeogenesis made?
A
From amino acid metabolism.
19
Q
Where is the glycerol used as a pre-cursor for gluconeogenesis made?
A
From lipids.
20
Q
In what organs will gluconeogenesis occur?
A
90% in the liver.
10% will occur in the kidneys
21
Q
Will gluconeogenesis occur in all cells?
A
No.
Only in the liver and kidney cells.
22
Q
How does gluconeogenesis get around the 3 irreversible steps of glycolysis?
A
It will bypass them.
23
Q
Where does the 1st step of gluconeogenesis occur?
A
In the cytoplasm and mitochondrial matrix.
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.
25
Where do the 2 pyruvate molecules that are transported into the mitochondrial matrix come from?
They come from the cytoplasm.
26
What enzyme converts the 2 pyruvate molecules to oxaloacetate in step 1 part 1?
Pyruvate carboxylase.
27
How does pyruvate carboxylase convert the 2 pyruvate molecules in step 1 part 1?
It adds a CO2 molecule to each pyruvate to form oxaloacetate.
28
Will pyruvate ever leave the cell?
No.
So, it will never be found in the bloodstream.
29
Where will the enzyme, pyruvate carboxylase be found?
Only in the liver and the kidneys.
30
Does pyruvate carboxylase require any co-enzymes?
Yes.
Biotin.
31
Is any energy used up in step 1 part 1 of gluconeogenesis where pyruvate is converted to oxaloacetate?
1 ATP.
32
How many pyruvates are produced per glucose molecule?
2.
33
Is step 1 of gluconeogenesis a reverse of the final step of glycolysis?
No.
Step 9 of glycolysis is irreversible so step 1 of gluconeogenesis must bypass it.
34
What happens in part 2 of step 1 of gluconeogenesis?
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.
35
Why is oxaloacetate converted to malate in part 2 of step 1 of gluconeogenesis?
Because oxaloacetate cannot cross the mitochondrial membrane
36
What enzyme converts oxaloacetate to malate?
Malate dehydrogenase.
37
Is any energy used in part 2 of step 1 of gluconeogenesis?
1 GTP.
38
How much total energy is used up per pyruvate molecule in step 1 of gluconeogenesis?
1 ATP.
1 GTP.
39
Is any energy generated in part 2 of step 1 of gluconeogenesis?
1 NADH.
40
How much energy is gained in step 1 of gluconeogenesis?
1 NADH.
41
What is the net spend of energy in step 1 of gluconeogenesis?
1 ATP.
1 GTP.
42
Can Phosphoenol pyruvate (PEP) be converted to fructose 1,6-bisphosphate by reversing glycolysis?
Yes.
All of the steps back to step 3 of glycolysis (7 of gluconeogenesis) are reversible.
43
Is step 7 of gluconeogenesis a reverse of step 3 of glycolysis?
No.
Step 3 of glycolysis is irreversible.
44
What location do steps 2-9 occur in gluconeogenesis?
In the cytoplasm.
45
What happens in step 7 of gluconeogenesis?
The phosphate group on carbon 1 is removed from the molecule to form fructose 6-phosphate.
46
What enzyme de-phosphorylates carbon 1 of fructose-1,6 bisphosphate in step 7 of gluconeogenesis?
Fructose 1,6-bisphosphatase.
47
The bi-functional enzyme that is used in step 3 of glycolysis and step 7 of gluconeogenesis is made up of what 2 enzymes?
Fructose 2,6-bisphosphatase (F 2,6 BPase).
Phosphofructokinase-2 (PFK-2).
48
Is step 8 of gluconeogenesis a reverse of step 2 of glycolysis?
Yes.
49
Where does step 9 of gluconeogenesis occur?
In the ER of the liver and in the cytoplasm.
50
What happens in step 9 of gluconeogenesis?
The phosphate group will be removed from carbon 6 of glucose 6-phosphate.
51
Is step 1 of glycolysis reversible?
No.
To form glucose, gluconeogenesis must bypass step 1 of glycolysis.
52
Where does the de-phosphorylation of glucose-6 phosphate occur?
In the ER of liver and kidney cells.
53
Can glucose 6-phosphate be released into the bloodstream?
No.
It must be converted to glucose 1st.
54
What transporter will release glucose into the bloodstream at the end of gluconeogenesis?
GLUT-2.
55
What transporter will take glucose between the cytoplasm and the ER of the liver of kidneys?
GLUT-7.
56
What enzyme will remove the phosphate group from glucose 6-phosphate in step 9 of gluconeogenesis?
Glucose 6-phosphatase.
57
Where can glucose 6-phosphatase be found?
In the endoplasmic-reticulum of kidney and liver cells.
58
In what steps of gluconeogenesis are ATP molecules used for energy?
Step 4.
Step 1.
59
How many ATP molecules are used in step 4 and step 1 of gluconeogenesis?
1 ATP per pyruvate.
2 ATP per glucose.
60
How much energy is used in gluconeogenesis to form a glucose molecule?
4 ATP molecules.
2 GTP molecules.
2 NADH molecules.
61
In total, how many ATPs are used up in gluconeogenesis?
12 ATP.
62
What are the regulated enzymes in gluconeogenesis and what steps are they used in?
Pyruvate carboxylase. (Step 1, part 1).
PEP carboxykinase. (Step 1, part 2).
Fructose 1,6-bisphosphatase. (Step 7).
63
What is pyruvate carboxylase activated by?
ACoA (allosterically).
64
Where will the ACoA that is used to activate pyruvate carboxylase be made?
By fatty acid oxidation.
65
What is fatty acid oxidation?
An additional energy source that can be used when glucose levels are low.
66
If the levels of ACoA in the liver increase, what will happen?
Pyruvate carboxylase will be stimulated.
67
What is pyruvate carboxylase inhibited by?
ADP.
68
What is PEP carboxykinase activated by?
Glucagon and ADP.
69
What is pyruvate carboxylase inhibited by?
ADP.
70
What hormone will cause an up-regulation of PEP carboxykinase?
Glucagon.
71
What is fructose 1,6-bisphosphatase activated by?
High levels of ATP.
Low levels of AMP.
72
What is fructose 1,6-bisphosphatase inhibited by?
Fructose 2,6 bisphosphate.
Low levels of ATP.
73
What type of activation does fructose 1,6-bisphosphatase have?
Allosteric and hormonal.
74
What type of inhibition does fructose 1,6-bisphosphatase have?
Allosteric.
75
Biotin is what form of co-enzyme?
A vitamin.
76
How does biotin help pyruvate carboxylase?
Biotin helps to transfer CO2 to pyruvate forming oxaloacetate.
77
What must be removed from the cell to allow fructose 1,6 bisphosphatase to work?
Fructose 2,6 bisphosphate.
78
Fructose 2,6 bisphosphate will activate what metabolic pathway?
Glycolysis.
79
Fructose 2,6 bisphosphate will inhibit what metabolic pathway?
Gluconeogenesis.
80
What enzyme will remove fructose 2,6 bisphosphate from the cell to allow gluconeogenesis to occur?
Fructose bisphosphatase-2.
81
What is fructose bisphosphatase-2 activated by?
Phosphorylation.
82
What pathway will activate the phosphorylation of FBPase-2?
PKA via the cAMP pathway which is activated by glucagon.
83
Does the phosphorylation of FBPase-2 use up any energy?
1 ATP.
84
What will FBPase-2 do once it is activated?
FBPase-2 will start to break down F 2,6-BP, removing it from the cell.
85
What happens once F2,6-BP can be removed from the cell?
F,1,6-BPase can form fructose 6 phosphate and gluconeogenesis to continue.
86
Is F2,6-BP made in gluconeogenesis or glycolysis?
No.
It is made via a side pathway.
87
What happens when the bi-functional enzyme is phosphorylated?
FBPase-2 will be inactive.
PFK-2 will be active.
88
What will lead to the phosphorylation of the bi-functional enzyme?
Insulin via the CAMP pathway.
89
What stimulates the synthesis of F 2,6-BP?
PFK-2.
90
What hormone stimulates gluconeogenesis?
Glucagon.
91
How will a rise in glucagon affect levels of fructose 2,6-bisphosphate?
It will lower them.
92
How does glucagon lower levels of fructose 2,6-bisphosphate?
Glucagon will activate the cAMP pathway which will phosphorylate the bi-functional enzyme allowing FBPase-2 to break down F 2,6-BP.
93
What does the break down of F 2,6-BP allow fructose 1,6 BPase to do?
To convert glucose 6-phosphate to glucose.
94
How will glucagon affect pyruvate kinase?
Glucagon activates the cAMP pathway and phosphorylates pyruvate kinase.
95
What stimulates the release of glucagon?
Low blood sugar.
96
Is pyruvate kinase inhibited when it is phosphorylated or when it is de-phosphorylated?
When it is phosphorylated.
97
The inhibition of pyruvate kinase results in the activation of what metabolic pathway?
Gluconeogenesis.
98
Will a rise in glucagon affect any the concentration of any allosteric effectors of glycolysis or gluconeogenesis?
It will lower levels of fructose 2,6-bisphosphate.
99
What will affect the rate of gluconeogenesis?
The availability of guconeogenic pre-cursors.
100
The availability of what gluconeogenic pre-cursor will result particularly affect the rate of gluconeogenesis?
Glucogenic amino acids such as keto acids.
101
Amino acids provide what for gluconeogenesis?
Carbon skeletons.
102
What amino acid is the most favoured precursor for gluconeogenesis?
Alanine.
103
What will activate hepatic pyruvate carboxylase during periods of starvation?
Acetyl CoA.
104
How is ACoA formed?
Via the beta-oxidation of these fatty acids.
105
Why is it important for ACoA levels to accumulate?
The accumulation of ACoA will stimulate pyruvate carboxylase to start gluconeogenesis.
106
The pre-cursors for gluconeogenesis are intermediates from what forms of metabolism
Protein and lipid metabolism?
107
How is glycerol produced?
Via the breakdown of fats during fasting.
108
What specific form lf fat is hydrolised to form glycerol?
Triacylglycerols.
109
What happens to the glycerol that is released from the oxidation of triacylglycerols?
It is delivered to the liver by the blood.
110
What happens to glycerol when it is delivered to the liver?
It will be phosphorylated to form DHAP.
111
What enzyme converts glycerol to DHAP?
Glycerol kinase.
112
Can DHAP enter gluconeogenesis?
Yes.
113
When is lactate released into the bloodstream?
By anaerobic glycolysis.
114
What cycle converts lactate to pyruvate?
The CORI cycle.
115
What happens in the CORI cycle?
Lactate will be picked up from the blood by the liver and will be converted to pyruvate.
116
What enzyme converts lactate to pyruvate?
Lactate dehydrogenase.
117
How can alanine be derived as a gluconeogenic pre-cursor?
From the natural degradation of muscle proteins.
118
What happens to the amino acids muscle proteins once they are degraded?
They are released into the blood and delivered to the liver.
119
What happens to the amino acids that are used for gluconeogenic pre-cursors once they enter the liver?
The keto-acids from alanine can be converted to pyruvate.
120
What is the conversion of alanine to pyruvate known as?
The alanine - pyruvate cycle.
121
What will happen to a person that has a heritable disease that results in a deficiency of glucose 6-phosphatase?
Glucose 6-phosphate cannot be converted to glucose.
This results in no release of glucose into the bloodstream.
122
What is the disease called when there is a deficiency in glucose 6-phosphatase?
Von Gierkes disease.
123
How will Von Gierkes disease affect an individual?
People who have this disease will become severely hypoglycaemic in the fasting state.
124
What are the glycolytic and gluconeogenic rate limiting enzymes in step 9 of glycolysis
Glycolysis. Pyruvate kinase.
Gluconeogenesis. Pyruvate carboxylase and PEP CK.
125
What are the glycolytic and gluconeogenic rate limiting enzymes in step 3 of glycolysis
Glycolysis. PFK-1.
Gluconeogenesis. Fructose 1,6-BPase.
126
What are the glycolytic and gluconeogenic rate limiting enzymes in step 1 of glycolysis
Glycolysis. Hexokinase and glucokinase.
Gluconeogenesis. Glucose 6-phosphatase.
