Gluconeogenesis And Glycogen Metabolism Flashcards

1
Q

What 6 tissues in the body require a continuous supply of glucose as a metabolic fuel?

A
  1. Brain
  2. Red blood cells
  3. Kidney medulla
  4. The lens and the cornea of the eye
  5. Testes
  6. Exercising muscle
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2
Q

How many grams of glucose does the brain need per day?

A

120g per day

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3
Q

How much glucose is in the body?

A

210g in total:
- 190g fro glycogen stores
- 20g circulating in the blood

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4
Q

How long can liver glycogen meet the demands of the body for once there is an absence from dietary input?

A

10-18 hours

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5
Q

Once glycogen stores are depleted, glucose can be formed from what precursors?

A
  • Lactate
  • Pyruvate
  • Glycerol
  • a-ketoacids
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6
Q

Why is pyruvate to glucose not a reverse of glycoloysis?

A
  • due to the 3 irreversible reactions in glycolysis this cannot occur
  • so glucose is then synthesised in a unique pathway
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7
Q

Where does around 90% of gluconeogenesis occur?

A

90% in the liver. The other 10% of newly synthesised glucose molecules are provided by the kidney

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8
Q

When do kidneys become a major role?

A

In prolonged starvation, as they will the become a major glucose producing organ

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9
Q

What are 3 unique reactions to gluconeogenesis?

A
  1. 3 irreversible reactions
  2. Bypass reactions
  3. Other reactions that are a reversal of glycolysis
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10
Q

What are the 3 irreversible reactions in Gluconeogenesis?

A
  1. Glucose —> Glucose-6-phosphate
  2. Fructose-6-phosphate—> Fructose 1,6 biphosphate
  3. Phosphoenolpyruvate —> pyruvate
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11
Q

What do the 3 bypass reactions involve and what do they do?

A

Bypass reactions are used to bypass the irreversible reactions

Bypass 1: Pyruvate kinase = 3 steps
Bypass 2: Phosphofructokinase = 1 step
Bypass 3: Hexokinase = 1 step

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12
Q

What is the definition of Gluconeogenesis?

A

Gluconeogenesis is the formation of glucose from a non-carbohydrate source

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13
Q

What is involved in bypass 1 of Gluconeogenesis?

A

Bypass 1= Pyruvate —> Phosphoenolpyruvate

Step 1:
Carboxylation of pyruvate.
Pyruvate —> oxaloacetate by the enzyme pyruvate carboxylase
Pyrvate carboxylase is only found in the mitochondria of the liver and kidney cells

Step 2:
Transport of oxalocetate to the cytosol
Oxalocetate is converted into malate by mitochondrial malate dehydrogenase. So it can cross the mitochondrial membrane where it is re-oxidised back into oxalocatete so it can enter the cytosol

Step 3:
Decarboxylation of cytosolic oxalocetate
Reaction driven by hydrolysis of GTP
PEP then enters the reversible reactions of glycolysis until it reaches fructose 1, 6 biphosphate

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14
Q

What happens in bypass 2 of Gluconeogenesis?

A
  • Dephosphorylation of fructose 1,6 biphosphae by hydrolysis.
  • Catalysed by enzyme fructose biphosphatase
  • important regulatory site of gluconeogenesis
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15
Q

What happens in bypass 3 of glucogeneonesis?

A
  • Glucose-6-phosphate —> glucose
  • Hydrolysis of glucose-6-phosphate bypasses the irreversible hexokinase reaction of glycolysis
  • glucose 6 phosphatase is present in the liver and kidney but NOT in muscle
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16
Q

Where does glucose 6 phosphatatse and pyruvate carboxylase occur?

A

In cells of the liver and kidney

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17
Q

What 2 things can contribute to the blood glucose pool?

A

Liver and Kidney.

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18
Q

What are gluconeogenic precursors?

A

Molecules that can give rise to a net synthesis of glucose

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19
Q

What do gluconeogenic precursors include?

A

All the intermediates of glycolysis and the citric acid cycle

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20
Q

What are the most important gluconeogenic precursors?

A
  1. Glycerol
  2. Lactate
  3. Alpha-ketoacids
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21
Q

What are the key features of the following gluconeogenesis precursor: Glycerol

A
  • released during hydrolysis of triaclglycerols in adipose tissue and is delivered in the blood to the liver
  • Glycerol is phosphorylated to glycerol phosphate, then oxidised to the glycolytic intermediate: dihydroxyacetone phosphate
  • Dihydroxyacetone phosphate —> Glyceraldehyde-3-phosphate
22
Q

What are the key features of the following gluconeogenesis precursor: Lactate

A
  • Released into blood by cells that lack mitochondria
  • end point of anerobic respiration
  • lactate is taken up by liver and converted to glucose which is released back into circulation
23
Q

What are the key features of the following gluconeogenesis precursor: alpha-ketoacids

A
  • contributes to liver glycogen in liver and muscle
  • amino acids whose catabolism yields pyruvate or one of the intermediates of the citric acid cycle are called glucogenic
24
Q

What happens when glycogen stores are depleted in the body?

A

The body synthesises glucose by gluconeogenesis

25
Q

What does the body store a reserve pool of glucose as?

A

The body stores a reserve pool of glucose in the form of glycogen

26
Q

What does the body need a constant store of and is of metabolic importance

A

The body needs a constant source of blood glucose

27
Q

What limits the production of glycogen in the body?

A

It is still unknown

28
Q

How many grams of glycogen makes up 1-2% of the fresh weight of resting muscle

A

400g glycogen

29
Q

100g glycogen makes up the fresh weight of what?

A

A well fed adult liver

30
Q

What are 4 features of glycogen structure?

A
  1. Branched chain homopolysaccharide made from alpha-D-Glucose
    2.Primary glycosidic bonds are alpha 1-4 and between every 8-10 residues there is a branch consisting of an alpha 1-6 glycosidic bond
  2. Molecular weight of <10^8
  3. Exist as discete cytoplasmic granules containing most of the enzymes for synthesis and breakdown
31
Q

What is the core of a glycogen granule made from?
And what are the benefits of its structure?

A

Made from the protien glycogenin and surrounded by branches of glucose polymers
Benefits= more space efficient, there is more glucose in the same space

32
Q

Where does glycogen synthesis occur and what energy does it need to happen?

A

Process occurs in the cytosol, requires energy in the form of ATP

33
Q

Glycogen is synthesised from what molecules?

A

Alpha-D-Glucose that are initially attached to uridine dihosphate

34
Q

What is UDP-glucose?

A

It is glucose attached to uridine diphosphate

35
Q

What is UDP-glucose the source of?

A

Source of all glucosyl residues that are added to the growing glycogen molecule

36
Q

What does step 1 of glycogen synthesis involve?

A
  • Glucose 6-phosphate is converted to glucose 1-phosphate by phosphoglucomutase
37
Q

What happens in step 2 of glycogen synthesis?

A
  • Synthesis of glycogen primer to initiate glycogen synthesis
  • main enzyme involved in gkycogen polymerisation
    -glycogen synthase is responsible for making the alpha 1-4 linkages in glycogen
  • glycogen synthesis requires a primer: glycogenin
38
Q

What are 3 key features of glycogenin?

A
  • Dimer of 2 identical 37kD units
  • Catalyses the addition of glucose to itself by covalently attatching glucose from UDP-glucose to the hydroxyl grou of tyrosine-194 in each subunit
    -Autocatalytic reaction facillitated by glycogen initiator synthase activity
39
Q

Glycogenin also has glucosyltransferase activity, What does this allow for?

A

The addition of up to 8 glucose residues from UDP-glucose to its partner in the glycogenin dimer in this sequence of autoglycosylations

40
Q

What happens in step 3 of glycogen synthesis?

A
  • Elongation of glycogen chains by glycogen synthase:
  1. Transfer of glucose from UDP-glucose to the non-reducing end of the growing chain
  2. Enzyme responsible for making these alpha 1-4 linkages in glycogen in glycogen synthase
  3. UDP released when the new alpha 1-4 linkage is formed an be converted back to UTP by nucleoside diphosphokinase
    UDP + ATP —> UTP + ADP
  4. Glycogen banching enzymes transfers the end of one chain to an earlier part of the chain by a 1,6 glycosidic bond
41
Q
  1. Which one of the following is NOT a characteristic of gluconeogenesis?
    a. It requires energy in the form of ATP or GTP.
    b. It is important in maintaining blood glucose during the normal overnight fast.
    c. It uses carbon skeletons provided by degradation of amino acids.
    d. It consists of all the reactions of glycolysis functioning in the reverse direction.
    e. It involves the enzyme fructose 1,6-bisphosphatase.
A

d. It consists of all the reactions of glycolysis functioning in the reverse direction.

42
Q
  1. Which one of the following reactions is unique to gluconeogenesis?
    a. Lactate —-> pyruvate
    b. Phosphoenolpyruvate —> pyruvate
    c. Oxaloacetate —> phosphoenolpyruvate
    d. Glucose 6-phosphate —> fructose 6-phosphate
    e. 1,3-Bisphosphoglycerate —> 3-phosphoglycerate
A

c. Oxaloacetate —> phosphoenolpyruvate

43
Q
  1. Which one of the following compounds cannot give rise to the net synthesis of glucose?
    a. Lactate
    b. Glycerol
    c. -Ketoglutarate
    d. Oxaloacetate
    e. Acetyl CoA
A

e. Acetyl CoA

44
Q
  1. Which one of the following statements concerning gluconeogenesis is correct?
    a. It occurs only in muscle.
    b. It is stimulated by fructose 2,6-bisphosphate
    c. It is inhibited by elevated levels of acetyl CoA
    d. It is important in maintaining blood glucose during the normal overnight fast.
    e. It uses carbon skeletons provided by the degradation of fatty acids.
A

d. It is important in maintaining blood glucose during the normal overnight fast.

45
Q
  1. Compared to the resting state, vigorously contracting muscle shows:
    a. An increased conversion of pyruvate to lactate.
    b. Decreased oxidation of pyruvate to CO2 and water
    c. A decreased NADH/NAD+ ratio
    d. Decreased concentration of AMP
    e. Decreased levels of fructose 2,6-bisphosphate
A

a. An increased conversion of pyruvate to lactate.

46
Q
  1. Muscle glycogen cannot contribute directly to blood glucose levels because:
    a. Muscle glycogen cannot be converted to glucose 6-phosphate
    b. Muscle lacks glucose 6-phosphatase
    c. Muscle contains no glucokinase
    d. Muscle contains no glycogen phosphorylase
    e. Muscle lacks phosphoglucoisomerase
A

b. Muscle lacks glucose 6-phosphatase

47
Q

Which one of the following compounds cannot give rise to the net synthesis of glucose?
a. Lactate
b. Glycerol
c. -Ketoglutarate
d. Oxaloacetate
e. Acetyl CoA

A

e. Acetyl CoA

48
Q
  1. An abnormal, poorly branched glycogen was isolated from the liver of a patient with type IV glycogen storage disease. The deficiency is most probably in:
    a. Phosphorylase kinase
    b. Glycogen phosphorylase
    c. Protein kinase A
    d. Amylo--(1,6)-glucosidase
    e. Amylo-alpha-(1,4–> alpha-1,6)-transglycosylase
A

e. Amylo-alpha-(1,4–> alpha-1,6)-transglycosylase

49
Q
  1. Liver glycogen can contribute directly to blood glucose levels because:
    a. Liver glycogen cannot be converted to glucose 6-phosphate
    b. Liver contains glucose 6-phosphatase
    c. Liver contains no glucokinase
    d. Liver contains no glycogen phosphorylase
    e. Liver lacks phosphoglucoisomerase
A

b. Liver contains glucose 6-phosphatase

50
Q
  1. Epinephrine and glucagon would have which of the following effects on glycogen metabolism in the liver:
    a. The net synthesis of glycogen is increased
    b. Glycogen phosphorylase is activated while glycogen synthase is inactivated
    c. Both glycogen phosphorylase and glycogen synthase are activated but at markedly different rates
    d. Glycogen phosphorylase is inactivated while glycogen synthase is activated
    e. cAMP-dependent protein kinase is activated while phosphorylase kinase is inactivated.
A

b. Glycogen phosphorylase is activated while glycogen synthase is inactivated