Chapter 13: Gluconeogenesis Flashcards
1
Q
Gluconeogenesis defined
A
- Synthesis of new glucose from non-carbohydrate sources
2
Q
Gluconeogenesis occurs in
A
- Primarily in the liver
- Also in the kidney cortex
3
Q
When liver glycogen is depleted
A
- Gluconeogenesis makes glucose available for the brain and RBCs
4
Q
ATP input required by gluconeogenesis
A
- Requires 6 ATP input
- Largely from beta oxidation of fatty acids
5
Q
Mobilization of fats
A
- Used in making ATP
6
Q
Gluconeogenic substrates
A
- First converted to oxaloacetate
7
Q
Pyruvate carboxylase (only in mitochondria)
A
- Converts pyruvate to oxaloacetate in order to bypass
8
Q
Major non-carbohydrate substrates for gluconeogenesis first converted to oxaloacetate
A
- Amino acids (ala/glu)
- CAC intermediates
- Glycolytic intermediates (Pyruvate, PEP)
- Lactate
- Glycerol
9
Q
Breakdown products of fatty acids, Acetyl-SCoA, and acetate
A
- No net synthesis of oxaloacetate from the breakdown of these products
10
Q
Solely ketogenic amino acid residues
A
- Leucine
- Lysine
11
Q
Hormone-sensitive lipase
A
- Mobilizes gluconeogenesis from glycerol originating from stored triacylglycerides
12
Q
Mobilization of gluconeogenesis from triacylglycerides requires
A
- Glycerol kinase
- Glycerol-3-phosphate dehydrogenase
13
Q
All reactions in gluconeogenesis
A
- All are irreversible and exergonic (spontaneous)
14
Q
3 irreversible steps in glycolysis that must be bypassed during gluconeogenesis
A
- Pyruvate kinase (PEP –> pyruvate)
- PFK-1 (F-6-P –> F-1,6-Bp)
- Hexokinase (glucose –> G-6-P)
15
Q
Mitochondrial pyruvate carboxyalse
A
- Converts pyruvate to oxaloacetate
- Anaplerotic reaction
16
Q
Oxaloacetate exits the mitochondria as either
A
- Aspartate (route 1)
- Malate (route 2)
17
Q
Outside the mitochondria
A
- Oxaloacetate can continue in gluconeogenesis
- Cytoplasmic PEPCK
18
Q
Mitochondrial PEPCK
A
- Converts oxaloacetate to PEP
- PEP can then exit the mitochondria directly through a translocase
19
Q
Malate dehydrogenase
A
- Uses up NAD
- Generates NADH
- Consequences for glycolytic pathway which will need NAD
20
Q
Anaplerotic reaction
A
- Topping off reaction
- OAA is an intermediate
- No depleting of the TCA intermediate
- So it doesn’t want to let OAA go
- Have to convert it via MDH or aspartate aminotransferserase
21
Q
Pyruvate kinase is irreversible
A
- Pyruvate cannot be converted to PEP by reversing this enzyme
22
Q
Fat is converted to Acetyl Co A
A
- Required for gluconeogenesis (everything is connected)
23
Q
Pyruvate carboxylase
A
- Anaplerotic reaction
- Converts pyruvate to oxaloacetate (exits the mitochondria as malate or aspartate)
- Solely in mitochondria
- Allosteric and biotin-dependent
- Requires Acetyl-SCoA as an obligate allosteric activator
24
Q
PEP carboxykinase
A
- Decarboxylation and phosphorylation of oxaloacetate to PEP
- Both cytoplasmic and mitochondrial in humans
25
PEP carboxykinase is over expressed in
- Diabetes
| - Leads to hyperglycemia
26
If diabetic and not in the starving state
- Glucose is still being made
27
Mitochondrial pyruvate carboxylase
- Forms OAA from pyruvate
28
NAHD-linked mitochondrial MDH
- Converts OAA to malate
29
Cytosolic MDH
- Reoxidizes malate in the cytosol to OAA
30
OAA is decarboxylated and phosphorylated in the cytoplasm by
- PEP carboxykinase
31
PEP in the cytosol
- Can by converted to fructose-1,6,-bisphosphate by glycolytic enzymes operating in reverse
32
If the cell needs energy
- Glycolytic pathway is favored and gluconeogenesis is inhibited
33
PFK-1 is irreversible and must be bypassed
- Bypass reaction is catalyzed by fructose-1,6-bisphosphate
- Stimulated by citrate
- Inhibited by AMP
34
Hexokinase is irreversible and must be bypassed
- Reaction is bypassed by a membrane-bound glucose-6-phosphatase
35
With high km of glucokinase in the liver
- Most glucose will not be phosphorylated and thus exit into circulation
36
Glucose-6-phosphatase
- ER membrane bound enzyme
| - Enzyme is absent from muscle tissue
37
Glucose-6-phosphatase absent from muscle tissue
- Causes muscle to use gluconeogenic enzymes to replenish glycogen not maintain BSL
38
Endoplasmic reticulum proteins
- Assist in the formation of glucose
| - From cytosolic G-6-P
39
Alcohol oxidation
- Primarily in liver (major site of gluconeogenesis)
40
Alcohol metabolism
- Reduces gluconeogenesis
| - Requires NAD+ or produces NADH
41
Cytosolic alcohol dehydrogenase
- Metabolizes ethanol to acetaldehyde
42
Mitochondrial acetaldehyde dehydrogenase
- Converts acetaldehyde to acetate
- Then to Acetyl-SCoA
- Then metabolized to CO2 and H2O
43
Alcohol metabolism shifts
- Shifts equilibrium of cytosolic lactate dehydrogenase from pyruvate formation to lactate synthesis
44
Alcohol metabolism favors
- Reduction of oxaloacetate to malate by cytosolic MDH
45
Reduction of oxaloacetate to malate
- Reduces OAA availability for gluconeogenesis
46
Increasing NADH results in
- Decrease in gluconeogenesis
| - Leads to hypoglycemia
47
Use of NAD+ by alcohol metabolism
- Impairs metabolism of pyruvate, urates, and fatty acids
- Reduces gluconeogenesis
- Leads to alcohol-induced hyperglycemia
48
Alcohol-induced hyperglycemia
- Affects the brain
| - Causes a drop in body temperature
49
Defective gluconeogenic activity
- Prevents lactate
| - Leads to lactic acidosis and fasting hypoglycemia
50
Under normal circumstances, in mature red blood cells (lacking mitochondria), and exercising muscle (under anaerobic conditions)
- The pyruvate end product of glycolysis is converted to lactate by lactate dehydrogenase
51
Lactate formation
- Reversible, but favored under physiological conditions
52
The Cori Cycle
- Lactate can diffuse out of the muscle cell
- Can be converted to glucose in the liver
- Cycle occurs in muscle and red blood cells
53
Gluconeogenesis uses
- Lactate
| - Pyruvate
54
Gluconeogenesis primarily uses C-skeletons of
- Alanine
| - Glutamate
55
Gluconeogenesis is essential for maintaining
- Blood sugar levels
56
Mobilization of gluconeogenesis from triacylglycerides produces
- Dihydroxyacetone phosphate/DHAP (glycolytic intermediate)
57
PEP carboxykinase synthesis is repressed by
- High glucose diets, but elevated in diabetes mellitus
