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Physiology Metabolism > Metabolism 4: Gluconeogenesis > Flashcards

Metabolism 4: Gluconeogenesis Flashcards

1
Q

What are the major gluconeogenic precursors?

A

Lactate, glucogenic amino acids, glycerol

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2
Q

Where does gluconeogenesis predominantly take place?

A

Liver and kidney

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3
Q

When using gluconeogenic amino acids as precursors, why is additional ATP needed?

A

To dispose the amino groups via ureagenesis

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4
Q

Do glycolysis and gluconeogenesis use the same set of enzymes?

A

No, they require separate enzymes

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5
Q

Does ethanol ingestion inhibit gluconeogenesis?

A

Yes and it can lead to hypoglycemia

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6
Q

Explain the process after consuming carbs?

A

Insulin dependent glucose transports to adipose, heart, skeletal muscle -> insulin independent glucose transports to liver and other tissues -> glycolysis is active -> PDH active in tissue with mitochondria t -> produce AcetylCoA -> Acetyl CoA metabolized/oxidized by CAC

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7
Q

What glycolytic enzyme genes does insulin promote the expression of in the liver in the fed state?

A

Glucokinase, PFK1, Pyruvate Kinase

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8
Q

What happens in a fasted/starved state?

A

Decrease glycolysis, increase gluconeogenesis and increase glycogenolysis (glycogen breakdown)

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9
Q

What role does glucagon/epinephrine play in glycolysis?

A

Block glycolysis by inhibiting pyruvate kinase and indirectly blocking PFK-1 by inhibiting PFK-2

Decrease transcription of glucokinase, PFK-1, pyruvate kinase

Promote glucose mobilization by glycogenolysis

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10
Q

What role does glucagon/epinephrine play in gluconeogenesis?

A

Promote it by increasing transcription and synthesis of key gluconeogenic enzymes

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11
Q

What are the 2 pathways necessary for glucose homeostasis and where do they take place?

A

Glycogenolysis
Gluconeogenesis

Liver

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12
Q

Why is G6P Phosphatase important in gluconeogenesis?

A

Need this enzyme to remove phosphate from G6P (generated from both gluconeogenesis and glycogenolysis paths) and create glucose. Without it, can end up with more glycogen

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13
Q

What stimulates gluconeogenesis?

A

low blood glucose via glucagon

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14
Q

How many ATP is required in gluconeogenesis?

A

6

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15
Q

Why is oxaloacetate important in gluconeogenesis?

A

Pyruvate is convereted to PEP in a 2 step process via oxaloacetate (“activated” form of pyruvatE)

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16
Q

What is required to form the “activated form” of pyruvate (oxaloacetate)?

A

Bicarb and cofactor biotin

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17
Q

Why is there a risk of hypoglycemia in neonates?

A

They are very dependent on glucose via glycogenolysis and gluconeogenesis, but it takes a few hours to induce PEP carboxykinase which is necessary to generate glucose from lactate or alanine

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18
Q

What is the sequence for glucoeneogenesis from lactate?

A

lactate -> pyruvate ->oxaloacetate -> PEP ——-> G6P ->glucose

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19
Q

What is the sequence for gluconeogenesis from alanine

A

alanine -> pyruvate ->oxaloacetate -> PEP ——-> G6P ->glucose

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20
Q

What is the sequence for gluconeogenesis from muscle protein?

A

Muscle protein -> aspartic acid -> oxaloacetate -> PEP —–> G6P ->glucose

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21
Q

What is the sequence for gluconeogenesis from triacylglycerol?

A

Triacylglycerol -> glycerol -> DHP —> G6P -> glucose

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22
Q

What does the cori cycle do?

A

Convert lactate from RBCs and skeletal muscles to glucose in liver

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23
Q

What does the alanine cycle do?

A

convert alanine (mostly from skeletal muscle) to glucose in the liver

releases ammonia during this gluconeogenic process

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24
Q

What is the conversion of fructose into lactate called?

A

fructolysis. the lactate can then be used in gluconeogenesis

25
Q

What is the sequence for fructolysis

A

fructose -> F1P -> DHAP + Glyceraldehyde 3 phosphate

Glyceraldehyde 3 phosphate -> lactate

26
Q

Why is galactose important for gluconeogenesis?

A

Can get you G6P which can be converted into glucose or used in glycolysis pathway

27
Q

During an overnight fast, what serves as the major source of ATP for gluconeogenesis?

A

Oxidation of fatty acids

28
Q

Can Acetyl-CoA undergo gluconeogenesis?

A

No. It has 2 C and we need a 3C compound. Will undergo either fatty acid synthesis of TCA

29
Q

What is glycerol a precursor for the synthesis of?

A

Triacylglycerols and phospholipids in the liver and adipose tissue

30
Q

What must glycerol be converted into before entering glycolysis or gluconeogenesis?

A

Glycerol-3-phosphate by glycerol kinase

31
Q

How is propionyl CoA formed

A

As a product of beta oxidation of odd chain fatty acids, isoleucine, valine, and alpha ketobutyric acid

32
Q

Why is propionyl CoA important

A

Good precursor for gluconeogenesis

Propionyl CoA -> Oxaloacetate -> glucose

33
Q

What are the 4 enzymes necessary to reverse the 3 irreversible steps of glycolysis?

A

Pyruvate Carboxylase (Mitochondria)
PEP Carboxykinase (Cytosol)
Fructose 1,6 bisphosphatase (cytosol)
Glucose-6-phosphatase (cytosol)

34
Q

What does mitochondrial pyruvate carboxylase do?

A

Convert 1 molecule of pyruvate to oxaloacetate using biotin

Activated by Acetyl-CoA

35
Q

What happens with pyruvate carboxylase deficiency?

A

Accumulation of pyruvate which gets converted to lactate by LDH leading to increased lactic acid

Also get increasing levels of alanine in serum as well

36
Q

What does PEP Carboxykinase do?

A

Convert Oxaloacetate into phosphoenolpyruvate using GTP

37
Q

What does Fructose 1,6 bisphosphatase do?

A

Removes 1phosphate from Fructose-1,6-bisphosphate to produce Fructose 6 phosphate

38
Q

What is Fructose 1,6 bisphosphatase inhibited by?

A

Fructose 2,6 bisphosphate, AMP

39
Q

What does Glucose 6 phosphatase do?

A

Remove phosphate from G6P to create glucose

40
Q

Is glucose 6 phosphatase present in skeletal muscle?

A

No. Can’t synthesize glucose here. Only use glucose or synthesize lacatate and send to liver

41
Q

How do we go from fructose 6 phosphate to glucose 6 phosphate in gluconeogenesis?

A

phosphoglucoisomerase

42
Q

Where is glucose 6 phosphatase located?

A

In the ER of liver, kidneyes, and intestines. G6P enters the luminal surface of the ER and gets converted by this enzyme to produce glucose

43
Q

What can result in accumulation of glycogen in the liver?

A

Genetic defect in either the G6P transproter or the G6Phophatase

44
Q

What happens with glucose 6 phosphatase deficiency?

A

Glycogen Storage Disease (Von Gierke)

Can’t convert G6P to glucose -> accumulate glycogen and fat in liver as well as elevated serum uric acid and elevated serum lactate

45
Q

What are some sx of G6phosphatase deficiency?

A

poor tolerance to fasting, growth retardation, hepatomegaly

46
Q

What are the control points in glycolysis and their reciprocal in gluconeogenesis?

A

Glucokinase:: Glucose 6phosphatase
Phosphofructokinase:: Fructose 1,6 bisphosphatase
Pyruvate Kinase:: Pyruvate Carboxylase/PEP Carboxykinase

47
Q

What regulates glucokinase?

A

+: insulin, glucose

48
Q

What regulates glucose 6 phosphatase?

A

+: glucagon

-: insulin, glucose

49
Q

What regulates phosphofructokinase?

A

+ F2,6bisphosphate, AMP

-: ATP, Citrate

50
Q

What regulates Fructose-1,6 bisphosphatase?

A

-: F2,6bisphosphate, AMP

51
Q

What regulates pyruvate kinase?

A

+: F1,6bisphosphate, glucose

-: glucagon, ATP

52
Q

What regulates PEP Carboxykinase?

A

+:glucagon

-: insulin

53
Q

What regulates pyruvate carboxylase?

A

+: Acetyl-CoA

54
Q

What generally increases the levels./synthesis of the glycolytic enzymes?

A

Increased insulin and glucose

Decreased cAMP due to decreased glucagon/epi

55
Q

What generally increases the levels./synthesis of the gluconeogenic enzymes?

A

Increased glucagon/epi
Starved/fasting
Increased cAMP

Less available energy (ATP)

56
Q

How does glucagon exert its gluconeogenic effect?

A

Alters the transcription of genes
Glucagon binds to receptor G protein -> AC -> increase cAMP -> inc PKA ->phosphorylate CREB -> upregulate transcription of enzymes

57
Q

How does ethanol metabolism cause hypoglycemia?

A

Increased NADH/H ratio -> promotes conversion of pyruvate and oxaloacetate into lactate and malate, thus removing them from the pool of gluconeogenic precursors

58
Q

Different NADH levels lead to what?

A

Increased NADH -> increased lactate formation

Decreased NADH -> decreased lactate formation

59
Q

What is the reaction for ethanol metabolism leading to hypoglycemia?

A

Ethanol + NAD -> Acetaldehyde + NADH + H+

Pyruvate + NADH + H -> Lactate + NAD+
Oxaloacetate + NADH + H -> Malate + NAD+

Physiology Metabolism (11 decks)

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