T1. GLUCONEOGENESIS Flashcards
(128 cards)
1
Q
What is the normal range of blood glucose concentration?
A
60–90 mg/100mL.
2
Q
What blood glucose level is lethal?
A
Below 40 mg/100mL.
3
Q
Why is glucose homeostasis important?
A
Variations outside normal glucose levels can cause diseases or death.
4
Q
Name the 3 types of diabetes.
A
Type I (autoimmune, insulin dependent)
Type II (multicausal, insulin resistance)
Transitory (during pregnancy)
5
Q
What happens in Type I Diabetes?
A
β-cells are destroyed; no insulin synthesis.
6
Q
What happens in Type II Diabetes?
A
Resistance to insulin; not all patients are insulin dependent.
7
Q
How much glucose does the CNS require daily?
A
160–180 g.
8
Q
How much glucose is stored in the body?
A
190 g as glycogen
20 g circulating
9
Q
How long can the body’s glucose reserves last?
A
About one day.
10
Q
What are the four glucose regulation phases after eating?
A
1.Exogenous phase (0–4h)
2.Post-absorptive phase (after 6h)
- Gluconeogenesis phase (after 16h)
4.Starvation phases (early and 5.late)
11
Q
What happens during the exogenous phase?
A
Glucose is absorbed after eating.
12
Q
What happens during the post-absorptive phase?
A
Glycogen is degraded, preparing for gluconeogenesis.
13
Q
When does the gluconeogenesis phase start?
A
After about 16 hours without eating.
14
Q
What happens after 2 days without eating?
A
Early starvation; glucose drops; only gluconeogenesis occurs.
15
Q
What energy source does the brain and CNS mainly use?
A
Glucose.
16
Q
Name 5 tissues that are glucose-dependent.
A
Brain/CNS
Muscle (during exercise)
Renal medulla
Blood cells (erythrocytes, leukocytes, lymphocytes)
Retina
17
Q
Name examples of highly proliferative, hypoxic tissues using glucose.
A
Intestinal mucosa
Skin
Testes
Tumors
18
Q
Which tissues mainly use fatty acids (FA) instead of glucose?
A
Skeletal muscle (resting)
Adipose tissue
Liver
Renal cortex
19
Q
Which tissues use ketone bodies or lactate as fuels?
A
Skeletal muscle (during contraction)
Cardiac muscle (lactate, FA, ketones)
Brain (extreme starvation: ketone bodies)
20
Q
Why can’t fatty acids fuel the brain under normal conditions?
A
FA can’t cross the blood-brain barrier.
21
Q
What is gluconeogenesis?
A
Synthesis of glucose from non-glucose precursors.
22
Q
What type of metabolic pathway is gluconeogenesis?
A
Anabolic.
23
Q
What are the main precursors for gluconeogenesis?
A
Lactate
Pyruvate
Amino acids
Glycerol
Citric acid cycle intermediates
24
Q
What does gluconeogenesis require?
A
ATP (from FA metabolism)
NADH (from lactate oxidation)
25
Besides energy, what else is needed for gluconeogenesis?
Carbon source to build glucose.
26
Where does gluconeogenesis mainly occur?
Liver (90%)
Renal cortex (10%)
27
Where in the cell does gluconeogenesis occur?
Mainly in the cytosol, but first step in mitochondria, third step in ER.
28
How many total reactions are in gluconeogenesis?
10 reactions.
29
How many gluconeogenesis reactions are shared with glycolysis?
6 reactions.
30
How many gluconeogenesis reactions are irreversible?
4 reactions.
31
How many glycolysis reactions are irreversible?
3 reactions.
32
What enzyme catalyzes Pyruvate --> Oxaloacetate?
Pyruvate carboxylase.
33
What enzyme catalyzes Oxaloacetate --> PEP?
PEPCK (Phosphoenolpyruvate carboxykinase).
34
What enzyme catalyzes F1,6BP --> F6P?
FBPase (Fructose-1,6-bisphosphatase).
35
What enzyme catalyzes G6P --> Glucose?
G6Pase (Glucose-6-phosphatase).
36
What enzyme catalyzes Glucose --> G6P?
Hexokinase (HK).
37
What enzyme catalyzes F6P --> F1,6BP?
Phosphofructokinase-1 (PFK-1).
38
What enzyme catalyzes PEP --> Pyruvate?
Pyruvate kinase (PK).
39
What happens in the pyruvate carboxylase reaction?
Pyruvate (3C) is converted to Oxaloacetate (4C).
40
What does the pyruvate carboxylase reaction consume?
1 ATP and biotin.
41
Where does the pyruvate carboxylase reaction occur?
In mitochondria.
42
What type of reaction is pyruvate carboxylase?
Anaplerotic.
43
What is the role of biotin in this reaction?
Biotin transfers a CO2‚ group.
44
Where does biotin come from?
Synthesized by gut bacteria or from diet.
45
What inhibits biotin absorption?
Raw eggs (contain avidin, which binds biotin).
46
What kind of molecule is biotin in this enzyme?
A prosthetic group.
47
What amino acid binds to biotin in pyruvate carboxylase?
Lysine.
48
What activates pyruvate carboxylase allosterically?
Acetyl-CoA.
49
What is the function of the flexible arm in pyruvate carboxylase?
Transfers CO2‚ from BC to CT domain.
50
How is oxaloacetate transported to the cytosol?
Converted to malate, transported, then oxidized.
51
What enzyme reduces oxaloacetate to malate?
Malate dehydrogenase.
52
Why is malate transport important for gluconeogenesis?
It provides NADH in the cytosol.
53
What does PEPCK convert?
Oxaloacetate to PEP.
54
What is removed and added in the PEPCK reaction?
CO2‚ is removed; phosphate is added.
55
What energy molecule does PEPCK consume?
1 GTP.
56
What are the two forms of PEPCK?
PEPCK-C (cytosolic) and PEPCK-M (mitochondrial).
57
Where does PEPCK function?
Liver and kidneys.
58
What type of reaction is PEPCK?
Anaplerotic.
59
When is PEPCK-C used?
Under normal conditions.
60
When is PEPCK-M used?
When lactate concentration is high.
61
What happens to lactate in the PEPCK-M pathway?
Lactate --> Pyruvate --> Oxaloacetate --> PEP.
62
What does lactate oxidation provide in this pathway?
Cytosolic NADH.
63
What determines which oxaloacetate transport pathway is used?
Type of precursor and energy needs.
64
Where do the reversible reactions of gluconeogenesis occur?
In the cytosol.
65
What does FBPase-1 do?
Hydrolyzes F1,6BP to F6P.
66
Is ATP produced in the FBPase-1 reaction?
No.
67
Why does F6P stay inside the cell?
Its negative charge prevents crossing the membrane.
68
What does glucose-6-phosphatase do?
Converts G6P to glucose.
69
Where does the G6Pase reaction take place?
In the endoplasmic reticulum (ER).
70
Is ATP generated in the G6Pase reaction?
No, only inorganic phosphate is released.
71
What is the common entry point for most gluconeogenesis precursors?
Oxaloacetate
72
Which precursor does NOT enter gluconeogenesis via oxaloacetate?
Glycerol
73
Which amino acids cannot serve as gluconeogenic precursors?
Lysine and Leucine
74
What types of molecules can be converted into gluconeogenesis precursors?
Amino acids, lactate, pyruvate, glycerol, odd-chain fatty acids
75
How is lactate produced in the body?
By reduction of pyruvate in anaerobic and hypoxic tissues
76
What happens to NADH in lactate production?
NADH is consumed and NAD+ is regenerated
77
What happens to lactate after it is produced in tissues?
It enters the bloodstream and is taken up by hepatic cells
78
What does hepatic oxidation of lactate yield?
Pyruvate, which enters gluconeogenesis
79
How are amino acids involved in gluconeogenesis?
They are degraded to pyruvate or CAC intermediates
80
Which amino acid is a major source of pyruvate?
Alanine
81
What is formed when alanine transfers its amino group to alpha-ketoglutarate?
Pyruvate and glutamate
82
What dual purpose do amino acids serve in gluconeogenesis?
Transport nitrogen and carbon skeletons
83
How is glycerol produced in the body?
By hydrolysis of triacylglycerols (lipolysis)
84
Where is glycerol absorbed and metabolized?
In hepatic cells
85
What does glycerol become after phosphorylation and oxidation?
Dihydroxyacetone phosphate (DHAP)
86
Are fatty acids gluconeogenic in mammals?
No, except odd-chain fatty acids
87
What gluconeogenic intermediate is produced from odd-chain fatty acid degradation?
Succinyl-CoA
88
What is the fate of most glucose consumed by peripheral tissues?
Converted to lactate, returned to liver for gluconeogenesis
89
What is a major irreversible loss of glucose from glycogen stores?
Complete oxidation of glucose, especially in the brain
90
What is the common entry point for most gluconeogenesis precursors?
Oxaloacetate
91
Which precursor does NOT enter gluconeogenesis via oxaloacetate?
Glycerol
92
Which amino acids cannot serve as gluconeogenic precursors?
Lysine and Leucine
93
What types of molecules can be converted into gluconeogenesis precursors?
Amino acids, lactate, pyruvate, glycerol, odd-chain fatty acids
94
How is lactate produced in the body?
By reduction of pyruvate in anaerobic and hypoxic tissues
95
What happens to NADH in lactate production?
NADH is consumed and NAD+ is regenerated
96
What happens to lactate after it is produced in tissues?
It enters the bloodstream and is taken up by hepatic cells
97
What does hepatic oxidation of lactate yield?
Pyruvate, which enters gluconeogenesis
98
How are amino acids involved in gluconeogenesis?
They are degraded to pyruvate or CAC intermediates
99
Which amino acid is a major source of pyruvate?
Alanine
100
What is formed when alanine transfers its amino group to alpha-ketoglutarate?
Pyruvate and glutamate
101
What dual purpose do amino acids serve in gluconeogenesis?
Transport nitrogen and carbon skeletons
102
How is glycerol produced in the body?
By hydrolysis of triacylglycerols (lipolysis)
103
Where is glycerol absorbed and metabolized?
In hepatic cells
104
What does glycerol become after phosphorylation and oxidation?
Dihydroxyacetone phosphate (DHAP)
105
Are fatty acids gluconeogenic in mammals?
No, except odd-chain fatty acids
106
What gluconeogenic intermediate is produced from odd-chain fatty acid degradation?
Succinyl-CoA
107
What is the fate of most glucose consumed by peripheral tissues?
Converted to lactate, returned to liver for gluconeogenesis
108
What is a major irreversible loss of glucose from glycogen stores?
Complete oxidation of glucose, especially in the brain
109
What are the three temporal levels of gluconeogenesis regulation?
Immediate (substrate availability & allosteric effectors), Fast (hormonal regulation), Slow (gene expression).
110
How does AMP affect glycolysis and gluconeogenesis?
AMP activates glycolysis by stimulating PFK-1 and inhibits gluconeogenesis by suppressing F1,6BPase.
111
What is the role of citrate in gluconeogenesis?
Citrate indicates high energy status and activates gluconeogenesis by inhibiting PFK-1.
112
How does fructose-2,6-bisphosphate regulate glycolysis and gluconeogenesis?
High levels activate glycolysis (stimulate PFK-1); low levels favor gluconeogenesis (activate FBPase-1).
113
What enzyme controls fructose-2,6-bisphosphate levels?
A bifunctional enzyme with PFK-2 and FBPase-2 activities, regulated by phosphorylation status.
114
How does glucagon influence gluconeogenesis?
Glucagon increases cAMP, activating PKA, which phosphorylates enzymes to promote gluconeogenesis.
115
How does insulin affect glycolysis?
Insulin activates phosphoprotein phosphatase 2A (PP2A), dephosphorylating enzymes to enhance glycolysis.
116
What is the long-term effect of fasting on gluconeogenic enzymes?
Increases expression of PEPCK, F1,6BPase, and G6Pase; decreases glycolytic enzymes like GK and PK.
117
How do thyroid hormones affect gluconeogenesis?
They increase expression of gluconeogenic enzymes, enhancing glucose production.
118
What is a substrate cycle in metabolism?
A set of opposing reactions (e.g., glycolysis and gluconeogenesis) that can amplify metabolic responses and generate heat.
119
What is the glucose-alanine cycle?
A process where muscles convert pyruvate to alanine, transport it to the liver, which reconverts it to glucose.
120
What is the Cori cycle?
A cycle where lactate produced by anaerobic glycolysis in muscles is transported to the liver and converted back to glucose.
121
How does glycerol contribute to gluconeogenesis?
Glycerol from adipose tissue is converted in the liver to dihydroxyacetone phosphate, entering gluconeogenesis.
122
Why can't fatty acids serve as gluconeogenic precursors?
Because their breakdown yields acetyl-CoA, which cannot be converted into glucose.
123
What is the exception to fatty acids not contributing to gluconeogenesis?
Odd-chain fatty acids yield propionyl-CoA, which can be converted to succinyl-CoA and enter gluconeogenesis.
124
How does alcohol consumption lead to hypoglycemia?
Alcohol increases NADH levels, inhibiting gluconeogenic enzymes like LDH and MDH, reducing glucose production.
125
What role do muscles play in gluconeogenesis?
Muscles provide lactate and alanine as substrates for hepatic gluconeogenesis.
126
How does adipose tissue support gluconeogenesis?
By releasing glycerol during lipolysis, which the liver uses for glucose production.
127
What triggers the switch from glycolysis to gluconeogenesis?
Low blood glucose levels, high AMP, and hormonal signals like increased glucagon.
128
How does high ATP affect glycolysis?
High ATP inhibits glycolytic enzymes like PFK-1, reducing glycolysis rate.
