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Fundamentals Of Life Science > Gluconeogenesis > Flashcards

Gluconeogenesis Flashcards

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1
Q

What does gluconeogenesis do?

A

Coverts non-carbohydrate substrates (pyruvate) into glucose

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2
Q

What can the non-carbohydrate substances be?

A

pyruvate, lactate, glycogenic amino acids, TCA cycle intermediates, odd-chain fatty acids

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3
Q

In mammals when does gluconeogenesis work?

A

fasting or starving state

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4
Q

Where does gluconeogenesis operate?

A

in liver and sometimes kidney

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5
Q

Is gluconeogenesis the simple reversal of glycolysis?

A

no because glycolysis has 7 reversible reactions but 3 non-reversible reactions and converts phosphoenolpyruvate to pyruvate directly whereas gluconeogenesis converts pyruvate to oxaloacetate and oxaloacetate to phosphoenolpyruvate

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6
Q

What is the cori cycle?

A

The cycle where pyruvate is converted into glucose in the liver and is then transported in the blood to a muscle where it is converted into pyruvate. The pyruvate is then converted into lactate which is transported in the blood to the liver where it is converted to pyruvate

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7
Q

How is pyruvate synthesised from lactate?

A

using the enzyme lactate dehydrogenase and converting NAD+ to NADH

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8
Q

How is glycerol prepared to be used as a precursor in gluconeogenesis?

A

Hydrolysis of triglycerides by lipase in adipose tissue to produce glycerol and fatty acids

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9
Q

How does glycerol become involved in gluconeogenesis?

A

its converted into dihydroxyacetone phosphate and introduced into gluconeogenesis. (using. glycerol kinase to convert it into glycerol-3-phosphate and then glycerol phosphate dehydrogenase to convert it into DHAP)

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10
Q

What can’t be used as a precursor for gluconeogenesis?

A

Fatty acids

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11
Q

What happens to fatty acids instead of being used for gluconeogenesis?

A

beta oxidation produces acetyl-CoA which enters into the TCA cycle to be decarboxylated.
FAs are the last source to enter into the TCA cycle

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12
Q

What happens when you use glycogenic amino acids as a precursor?

A
  • Catabolism of these amino acids yields pyruvate or one of the intermediates of the TCA cycle
  • These intermediates acts as a substrate for gluconeogenesis
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13
Q

What are the metabolic reactions different to gluconeogenesis?

A

Pyruvate to oxaloacetate

Oxaloacetate to phosphoenolpyruvate

Fructose-1,6-bisphosphate to fructose-6-phosphate

Glucose-6-phosphate to glucose

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14
Q

What is the reaction converting pyruvate to oxaloacetate?

A

pyruvic acid + CO2 + H2O =oxaloacetic + Pi

using pyruvate carboxylase and ATP

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15
Q

How does the reaction converting pyruvate to oxaloacetate work?

A

-3 stage process involving CO2 activation, followed by binding to a biotin binding site on enzyme followed by carboxylation of pyruvate

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16
Q

Where does the reaction converting pyruvate to oxaloacetate occur?

A

Mitochondria

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17
Q

How is oxaloacetate exported out of the mitochondria to the cytosol?

A
  • in the mitochondria oxaloacetate is reduced to malate (with production of NAD+)
  • malate is transported to the cytosol where it is oxidised to oxaloacetate to produce NADH
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18
Q

How is oxaloacetic acid converted to phosphoenolpyruvate?

A

-It uses one GTP (donates P)
-PEP carboxykinase as the enzyme
and produces CO2

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19
Q

How do you convert fructose-1,6-biphosphate to fructose-6-phosphate?

A
  • hydrolysis reaction of a phosphoric acid monoester (lose phosphate from 1 position)
  • uses fructose-1,6-biphosphatase
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20
Q

What is the net reaction of gluconeogenesis?

A

2 pyruvate + 4ATP + 2GTP + 2NADH + 6H2O

glucose + 4ADP + 2GDP + 6Pi + 2NAD+ + 2H+

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21
Q

What is the net reaction of the reverse of glycolysis?

A

2 pyruvate + 2ATP + NADH + 2H2O

glucose + 2ADP + 2Pi + 2NAD+ + @H+

22
Q

Does gluconeogenesis require the catabolism or anabolism of ATP?

A

Catabolism (breakdown)

23
Q

What drives the energetically unfavorable reactions of gluconeogenesis?

A

Nucleoside triphosphate hydrolysis

24
Q

What pathways are active and inactive when energy is needed?

A
  • glycolysis active

- gluconeogenesis inactive

25
Q

What happens when energy is in excess or not needed and biosynthetic intermediates are in excess?

A

gluconeogenesis is active

26
Q

How are the pathways regulated so only glycolysis or gluconeogenesis is occurring at once?

A
  • pathway enzymes are regulated to provide operation of one pathway only
  • metabolites provide an inhibitory or stimulatory allosteric effect
27
Q

What is the role of fructose-2,6-biphosphate and how is it synthesised?

A
  • signalling molecule
  • stimulates phosphofructokinase
  • strongly inhibits fructose-1,6-bisphosphate

Synthesised by PFK2

28
Q

why is fructose-2,6-bisphosphate important in low blood glucose levels?

A
  • increase in hormone glucagon which signals a cyclic AMP signal cascade leading to phosphorylation by protein kinase A
  • This activates FBPase2 and inhibits PFK-2 leading to a decrease in fructose-2,6-biphosphate, allowing glyconeogenesis to operate predominantly
29
Q

why is fructose-2,6-bisphosphate important in low blood glucose levels?

A
  • gluconeogenesis not needed
  • insulin is secreted and initiates a signal pathway that activates a protein phosphatase which dephosphorylates the bifunctional enzyme
  • this activates PFK and inhibits FBPase2 leading to an increase in fructose-2,6-biphosphate, allowing glycolysis to operate
30
Q

What is glycogen?

A

storage form of glucose in mammals

31
Q

Why is glycogen important for storage?

A

-high levels of glucose would disrupt osmotic balance and damage cells (glycogen not osmotically active)

32
Q

Where is glycogen stored?

A

in the liver and skeletal muscles (also present in cytoplasm as granules)

33
Q

What types of glycosidic bonds are there in glycogen?

A
  • α-1,4-glycosidic bonds (lead to open helical polymers)

- α-1,6-glycosidic bonds (lead to branches)

34
Q

What is the role of glycogen?

A
  • used to provide glucose for ATP production

- fuel reserve

35
Q

What is glycogenolysis?

A

when glycogen is enzymatically degraded to remove glucose units to produce glucose-1-phosphate

36
Q

What are the enzymes important in glycogen breakdown and production?

A
  • glycogen synthase

- glycogen phosphorylase

37
Q

What enzyme breaks down glycogen to glucose-1-phosphate?

A

Glycogen phosphorylase

38
Q

What enzyme breaks down glucose-1-phosphate to glucose-6-phosphate?

A

phosphoglucomutase

39
Q

When is glycogen phosphorylase active?

A

When its phosphorylated

40
Q

What is glycogen phosphorylase regulated by?

A
  • ATP (inhibition)
  • glucose-6-phosphate (inhibition)
  • AMP (activation)
41
Q

How are GP and GS initiated?

A

through hormone triggered cyclic-AMP cascades

42
Q

Where is insulin produced?

A

beta cells of pancreas

43
Q

What does insulin do?

A
  • increases the rate of glucose transport into cells/tissues via GLUT 4 transporter
  • stimulates liver glycogen synthesis
44
Q

Where is glucagon produced?

A

in the α cells of the pancreas

45
Q

What is the role of glucagon?

A
  • stimulates glycogen degradation

- only used in liver cells rich in glucagon receptors

46
Q

What happens in Von Gierke disease?

A

the enzyme glucose-6-phosphase is defective

  • can not release glucose from glucose-6-phosphate
  • increased amount of glycogen
47
Q

What are the symptoms of Von Gierke disease?

A
  • enlarged liver through glycogen levels
  • hypoglycaemia because glucose can not be released in fasted state
  • ketosis as glucose-6-phosphate passes through glycolysis to produce high levels of pyruvate and lactate in the liver (released to blood)
  • hyperlipidemia
  • failure to thrive
48
Q

What is the defective enzyme in cori disease?

A

amyloid-1,6-glucosidase (debranching enzyme)

causes increased amount of glycogen with shorter outer structure and produces milder forms of VGs

49
Q

What is the defective enzyme in McArdle’s disease?

A

glycogen phosphorylase (can not release glucose from glycogen)

50
Q

What is the effected organ in McArdle’s?

A

muscle

51
Q

What effects does McArdle’s have?

A

increased amount of glycogen with a normal structure

Fundamentals Of Life Science (26 decks)

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