Gluconeogenesis Flashcards

(113 cards)

1
Q

Increased NADH leads to _______ lactate formation

A

Increased

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2
Q

Decreased NADH leads to _______ lactate formation

A

Decreased

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3
Q

What is the effect of ethanol metabolism on the NADH/NAD ratio?

A

Increases it

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4
Q

When you consume ethanol, you become hyper/hypoglycemic?

A

Hypoglycemic

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5
Q

When consuming ethanol, oxaloacetate is depleted as a precursor and instead converted into ________

A

Malate

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6
Q

When consuming alcohol, pyruvate is depleted as a precursor and instead converted to ___________

A

Lactate

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7
Q

What enzyme is needed for the following reaction?

Glucose 6-phosphate –> glucose

A

Glucose 6-phosphatase

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8
Q

What enzyme is needed for the following reaction? Fructose 1,6-bisphosphate –> Fructose 6-phosphate

A

Fructose 1,6-bisphosphatase

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9
Q

What enzyme is needed for the following reaction? Oxaloacetate –> phosphoenolpyruvate

A

Phosphoenolpyruvate carboxykinase

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10
Q

What enzyme is needed for the following reaction?

pyruvate –> oxaloacetate

A

Pyruvate carboxylase

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11
Q

What is the sum of the reaction of mixing pyruvate with ethanol?

A

Ethanol + Pyruvate –> Acetaldehyde + lactate

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12
Q

What is the sum of the reaction of oxaloacetate and ethanol?

A

Ethanol + oxaloacetate –> acetaldehyde + malate

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13
Q

High NADH _________ gluconeogenesis

A

Opposes

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14
Q

Removal of pyruvate and OAA from the pool of gluconeogenic precursors during alcohol metabolism contributes to what condition?

A

Hypoglycemia

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15
Q

What are the irreversible enzymes of glycolysis?

A

Glucokinase, PFK1, and pyruvate kinase

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16
Q

What hormone increase the synthesis of glycolytic enzymes

A

Insulin

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17
Q

What hormones increase the synthesis of gluconeogenic enzymes?

A

Glucagon and epinephrine

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18
Q

What are the 4 irreversible enzymes of gluconeogenesis?

A

Glucose-6-phosphatase, Fructose 1,6-bisphosphatase, Phosphoenolpyruvate carboxykinase, and pyruvate carboxylase

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19
Q

What is an example of glucagon altering gene expression?

A

PEPCK

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20
Q

How does glucagon alter gene transcription?

A

Glucagon acts on a GPCR glucagon receptor, and Gs stimulates adenylate cyclase to produce cAMP. cAMP activate PKA, which facilitates the conversion of CREB to CREB-P. CREB-P turns on CRE, promoting PEPCK transcription

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21
Q

Which state, fed or fasted, would increase synthesis of gluconeogenic enzymes?

A

Starvation/Fasted states

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22
Q

What is the effect of increased cAMP on gluconeogenic enzymes

A

Increased synthesis

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23
Q

What is the effect of insulin and glucose on gluconeogenic enzymes

A

Decreased synthesis

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24
Q

What is the effect of insulin and glucose on glycolytic enzymes

A

increased synthesis

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25
What is the effect of decreased cAMP on glycolytic enzymes?
Increased synthesis
26
What is the effect of elevated acetyl coA on pyruvate carboxylase and subsequently gluconeogenesis
Activator, increases pyruvate --> phosphoenolpyruvate, increases gluconeogenesis
27
What is the effect of increased glucagon on PEPCK?
Activator, increases phosphoenolpyruvate --> oxaloacetate
28
What is the effect of insulin on PEPCK?
Inhibits it (since you must be fed if you have insulin circulating)
29
What are the activators of pyruvate kinase in glycolysis?
F-1,6-BP, glucose
30
What are the inhibitors of pyruvate kinase in glycolysis?
Glucagon and ATP
31
What is the reaction catalyzed by F16BPase?
Fructose 1,6-bisphosphate to fructose 6-Phosphate
32
What are the inhibitors of F16BPase
F26BP and AMP
33
What are the inhibitors of phosphofructokinase in glycolysis
ATP and citrate
34
What are the activators of PFK in glycolysis
F26BP and AMP
35
What are the effects of each of the following on G6Pase 1. insulin 2. glucagon 3. Glucose
1. inhibits 2. promotes 3. inhibits
36
What are the effects of insulin and glucose on glucokinase
Promote
37
What is the reaction catalyzed by Glucose-6-phosphatase
G6P to glucose
38
Is G6Pase deficiency dominant or recessive?
Autosomal recessive
39
What is another term for G6Pase deficiency
GSD type 1, or Von Gierke disease
40
What are the characteristics of G6Pase deficiency
poor tolerance to fasting, growth retardation, hepatomegaly due to accumulation of glycogen and fat in the liver, elevated serum uric acid, and elevated serum lactate
41
What processes are inhibited by a G6Pase deficiency?
Gluconeogenesis and glycogenolysis
42
What step is inhibited by a G6Pase deficiency
Conversion of G6P to glucose
43
What enzyme is only found in the liver, kidney, and intestines that is important for gluconeogenesis and glycogenolysis
G6Pase
44
Which side of the ER does the catalytic surface of G6Pase face?
Lumen
45
What transporter does glucose 6 phosphate enter the ER through?
ubiquitous transporter
46
What are the steps to get from F16BP and water to Glucose and Pi
F16bp+H20 --F16BPase--> F6P+Pi G6P+H20 --G6Pase--> Glucose+Pi
47
What reaction is inhibited by F26BP and AMP
F16BPase (F16BP -> F6P +Pi)
48
What energy-carrying molecule is required by PEPCK?
GTP
49
What reaction is catalyzed by PEPCK?
Oxaloacetate + GTP --> PEP + CO2 + GDP
50
Why would PC (pyruvate carboxylase) deficiency cause acidosis?
Elevated lactic acid levels
51
What are symptoms of someone who has PC deficiency?
failure to thrive, developmental delay, recurrent seizures, metabolic acidoses
52
What accumulates in PC deficiency?
Pyruvate in the plasma, which converts to lactate by LDH, causing elevated plasma lactic acid
53
What is found in the serum of someone with PC deficiency?
High alanine
54
Why would gluconeogenesis and urea cycle both be inhibited as a result of PC deficiency?
Because 1. pyruvate would not convert to OAA 2. OAA is a precursor for aspartate, which is a precursor for both urea cycle and gluconeogenesis
55
Is PC a mitochondrial enzyme or a cytoplasmic enzyme?
Mitochondrial
56
What cofactor does PC require?
biotin
57
What molecule activates PC?
Acetyl CoA
58
What reaction does pyruvate carboxylase catalyze?
Pyruvate --> OAA
59
What high-energy molecule does PC need to work?
ATP
60
What are the 4 control points of gluconeogenesis
G6Pase, F16BPase, PEPCK, and PC
61
What are the 3 control points of glycolysis?
Hexokinase, PFK, pyruvate kinase
62
What are the mitochondrial enzymes required to reverse the irreversible steps of glycolysis?
PC
63
What are the cytoplasmic enzymes required to reverse the irreversible steps of glycolysis?
F16BPase, PEPCK, and G6Pase
64
Propionyl CoA is a good precursor for ______
Gluconeogenesis
65
What does propionyl CoA form as a result of?
B-oxidation of odd-chain FA, isoleucine, valine, and alpha-ketoburytuc acid
66
How much glucose is produced from 1 propionyl CoA?
1/2
67
What gluconeogenic precursor does propionate form?
Oxaloacetate
68
Glycerol is a precursor for the synthesis of _____ and _____ in the liver and adipose tissue
TAGs and phospholipids
69
What reaction is catalyzed by glycerol kinase
Glycerol --> glycerol 3-phosphate (which goes into fat)
70
What reaction is catalyzed by glycerol 3-phosphate dehydrogenase?
Glycerol 3-phosphate --> Dihydroxyacetone phosphate
71
What can be made from dihydroxyacetone phosphate?
1/2 glucose molecule or lactate
72
What high energy molecule is needed by glycerol kinase
ATP
73
What high energy molecule is needed for glycerol 3-phosphate dehydrogenase?
NAD+ (gets reduced to NADH)
74
What gluconeogenic precursor does glycerol form?
triose phosphate
75
Can acetyl-CoA be used to make glucose?
No. It is committed to either FA synthesis or Krebs cycle
76
What forms Acetyl CoA?
Breakdown of FA and pyruvate via PDH
77
Gluconeogenesis from all precursors requires ____
ATP
78
Gluconeogenesis from amino acids requires ____ ATP, which is used for ___
additional; ureagenesis
79
What is the major source of ATP for gluconeogenesis during an overnight fast?
Oxidation of FAs
80
What reaction does galactokinase catalyze?
Galactose --> Galactose-1-phosphate
81
What reaction does UDP-Glc:Gal-1-P Uridyltransferase catalyze?
Galactose-1-phosphate --> glucose-1-phosphate
82
What reaction does phosphoglucomutase catalyze?
Glucose-1-P --> Glucose-6-P
83
What reaction does glucose-6-phosphatase catalyze
G6P --> Glucose
84
Which step of the process from galactose to glucose requires ATP?
Galactokinase (galactose --> galactose-1-P)
85
Which precursor can be used to directly synthesize glucose?
Galactose
86
Define fructolysis
Conversion of fructose into lactate
87
What reaction does fructokinase catalyze?
Fructose --> F1P
88
What reaction does aldolase B catalyze?
F1P --> glyceraldehyde + dihydroxyacetone phosphate
89
What reaction does triose kinase catalyze?
Glyceraldehyde --> lactate
90
Which steps of fructolysis require ATP?
Fructokinase (fructose --> F1P) and triose kinase (glyceraldehyde --> Glyceraldehyde 3P)
91
What gluconeogenic intermediate is formed from fructose?
triose phosphate
92
What is the cori cycle?
Using glucose to make lactate
93
What are the steps of the Cori cycle starting from glucose in the liver
Glucose enters RBC, glycolysis happens, 2ATP and 2 Lactate are produced, the 2 lactate can return to the liver to be used for gluconeogenesis
94
How many ATP does 2 Lactate --> Glucose require?
6
95
How does pyruvate become alanine in the skeletal muscle during the alanine cycle?
It is transaminated
96
What is the fate of alanine entering the liver?
Ureagenesis and deamination to produce pyruvate for gluconeogenesis
97
How many ATP are required to go from 2 pyruvate to glucose?
6
98
What gluconeogenic intermediate is formed by amino acids like alanine and by lactate?
Pyruvate
99
Where does lactate for pyruvate generation for gluconeogenesis come from?
Glycolysis in other tissues
100
Where does the aspartic acid for OAA comes from for gluconeogenesis?
Breakdown of muscle protein
101
Where does the glycerol for dihydroxyacetone phosphate for gluconeogenesis come from?
TAG
102
What do trioses get converted into in gluconeogenesis?
F16BP
103
Why are neonates at risk for hypoglycemia?
Because it takes hours to induce PEPCK to make glucose from lactate or alanine
104
Neonate's brain is very dependent on glucose from ____ and _____
glycogen degradation and gluconeogenesis
105
What are the 3 major gluconeogenic precursors
Lactate, glucogenic AAs like alanine, and glycerol
106
Where do we get lactate as a gluconeogenic precursor?
general metabolism, RBC metabolism, muscle metabolism
107
Where do we get glucogenic AAs like alanine as precursors for gluconeogenesis?
Overnight degradation of muscle AAs
108
Where do we get glycerol as a precursor for gluconeogenesis
degradation of adipose tissue triacylglycerols
109
Oxaloacetate can be viewed as an _______ form of pyruvate
activated
110
The two mechanisms of maintaining glucose levels are _________
gluconeogenesis and glycogen
111
Glucagon and epinephrine have 3 effects during starvation, what are they?
1. promote gluconeogenesis 2. increase gene transcription of gluconeogenic enzymes 3. promote mobilization of glucose via glycogen degradation
112
How do glucagon/epinephrine block glycolysis?
Inhibit PFK2 to inhibit PFK1
113
What three genes do glucagon and epinephrine decrease gene transcription of?
Glucokinase, PFK1, and pyruvate kinase