Gluconeogenesis Flashcards

1
Q

What is gluconeogenesis ?

A

glucose formation from non carbohydrate precursors

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2
Q

What is the daily requirement for glucose ?

A
  • 160g
  • brain uses 120g of this
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3
Q

What is the main site of gluconeogenesis ?

A
  • major site is the liver
  • in extreme circumstances can happen in kidneys also
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4
Q

Is gluconeogenesis the reverse of glycolysis ?

A

NO !!
it is not the reverse of glycolysis

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5
Q

What is the role of gluconeogenesis ?

A

it helps to maintain blood glucose levels so the muscles and brain can extract it

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6
Q

How does gluconeogenesis happen ?

A
  • precursors are first converted into pyruvate or enter the pathway further along
  • pyruvate is converted into glucose
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7
Q

What are the major precursors for gluconeogenesis ?

A
  • lactate
  • amino acids
  • glycerol
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8
Q

Where is lactate produced ?

A
  • lactate is produced in skeletal muscles
  • produced when glycolysis exceeds oxidative metabolism
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9
Q

Which amino acids are not precursors for gluconeogenesis ?

A
  • leucine
  • lysine
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10
Q

Where is glycerol found ?

A
  • found in fat cells
  • triglycerides are hydrolysed into glycerol and fatty acids
  • glycerol is hydrophilic and so it can be transported to the liver and converted to glucose
  • fatty acids can’t b converted into glucose
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11
Q

Describe difference between glycolysis and gluconeogenesis

A

glycolysis : glucose to pyruvate
yields 2 ATP and 2 NADH

gluconeogenesis : pyruvate to glucose
requires 6 ATP and 2 NADH

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12
Q

Which 3 steps of glycolysis are irreversible ?

A
  • hexokinase
  • phosphofructokinase
  • pyruvate kinase
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13
Q

What happens to these steps in gluconeogenesis ?

A

these 3 steps must be bypassed in gluconeogenesis

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14
Q

What is the first bypass that happens in gluconeogenesis ?

A
  • pyruvate is converted into phosphoenol-pyruvate
  • this is a 2 step process :
    1) pyruvate is carboxylated to oxaloacetate by pyruvate carboxylase and this requires energy from ATP
    2) oxaloacetate is decarboxylated and phosphorylated to phosphoenol-pyruvate by phosphoenolpyruvate carboxykinase and this requires GTP
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15
Q

Where is the phosphoenolpyruvate carboxykinase enzyme located ?

A

it is located in both the cytosol and mitochondria

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16
Q

When is mitochondrial phosphoenolpyruvate used ?

A
  • it is used if lactate is the glucogenic precursor
  • lactate to pyruvate yields NADH
  • the NADH generated in the cytosol is used further up in the pathway
17
Q

When is cytosolic phosphoenolpyruvate used ?

A
  • it is used if pyruvate is the glucogenic precursor
  • used if NADH is needed
18
Q

Describe the oxaloacetate shuttle

A
  • oxaloacetate cannot directly diffuse out the mitochondria
  • it is converted to malate which leaves via a specific transporter
  • NADH is oxidised to NAD+ in the mitochondria
  • malate is converted back to oxaloacetate by malate dehydrogenase in the cytosol
  • NAD+ is reduced to NADH in the cytosol
  • oxaloacetate can then be converted to phosphoenol-pyruvate
19
Q

Describe how lactate is converted into pyruvate

A
  • lactate is converted into pyruvate via lactate dehydrogenase and this yields NADH
  • this takes place in the cytosol
20
Q

What is the overall reaction of bypass 1 ?

A

pyruvate + ATP + GTP + H2O > PEP + ADP + GDP + 2H+ + Pi

21
Q

What happens between bypass 1 and bypass 2 ?

A

glycolytic enzymes will work in reverse

22
Q

What is the second bypass that happens in gluconeogenesis ?

A

fructose 1,6 - bisphosphate is converted to fructose 6 - phosphate by the enzyme fructose 1,6 - bisphosphatase

fructose 1,6 - bisphosphate + H2O > fructose 6 - phosphate + Pi

23
Q

What is the third bypass that happens in gluconeogenesis ?

A

glucose 6 - phosphate is converted to glucose by glucose 6 - phosphatase
- this happens in the endoplasmic reticulum
- this enzyme is only found in the liver and kidney

24
Q

Explain why the brain and skeletal muscles lack the glucose 6 - phosphatase enzyme

A
  • the brain doesn’t want to turn glucose 6 - phosphate into glucose which can then enter the bloodstream because it is very reliant on glucose
  • in muscles glucose is used for the fight or flight response
25
Q

How are glycolysis and gluconeogenesis reciprocally regulated ?

A
  • high glucose levels
  • insulin released
  • increases levels of fructose 2,6 - bisphosphate
  • glycolysis activated
  • gluconeogenesis inhibited
  • low glucose levels
  • glucagon released
  • decreases levels of fructose 2,6 - bisphosphate
  • inhibits glycolysis
  • activates gluconeogenesis
26
Q

What is fructose 2,6 - bisphosphate ?

A
  • it is a small molecule which modulates the activity of phosphofructokinase and fructose 1,6 - bisphosphatase
  • it is a positive allosteric effector for phosphofructokinase
  • it is a negative allosteric effector for fructose 1,6 - bisphosphatase
  • levels of this molecule are controlled by insulin and glucagon
27
Q

Why is lactic acid produced during anaerobic activity ?

A
  • during extreme muscular activity oxygen delivery to the muscle is lower than oxygen requirements for oxidation of NADH
  • NADH is oxidised by the transfer of electrons to pyruvate to form lactic acid
28
Q

Briefly describe the role of lactate and pyruvate in the Cori cycle

A
  • lactate is produced by active muscle and red blood cells
  • well oxygenated cells will convert lactate to pyruvate which enters the Cori cycle
  • excess lactate enters the liver and is converted to glucose and this maintains blood glucose levels