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Metabolism > Carbohydrates- Glycogenesis, Glycogenolysis and Gluconeogenesis > Flashcards

Carbohydrates- Glycogenesis, Glycogenolysis and Gluconeogenesis Flashcards

1
Q

When does glycogenesis occur?

A

Occurs after a meal

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2
Q

When does glycogenolysis occur?

A

When blood glucose drops

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3
Q

When does gluconeogenesis occur?

A

When glycogen stores have been depleted

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4
Q

What is the role of glucose-6-phosphate dehydrogenase?

A

Removes glucose-6-phosphate from glycolysis

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5
Q

What happens in the fed state?

A
  • Glycogenesis- making and depositing glycogen

- Increased insulin and decreased glucagon

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6
Q

What happens in the prolonged fast?

A

Depleted glycogen (after glycogenolysis)

  • Gluconeogenesis
  • lactate
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7
Q

What are the sources of blood glucose?

A
  • Dietary-first source
  • Glycogenolysis from liver
  • Gluconeogenesis from carbon sources (final source)
  • Carbon from lactate, glycerol (Triglycerides in adipose)
  • Longest fasting period is overnight
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8
Q

What is the role of glycogen?

A
  • Storage

- Responsible for maintaining blood glucose between meals, preventing hypoglycaemia

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9
Q

Describe the structure of glycogen

A
  • Branched polymer
  • ~60,000 units linked by α-1,4-glycosidic bond (backbone) or α-1,6-glycosidic bond for branches
  • Most glycogen found as granules in cytoplasm, small amount stored and degraded in lysosome (difficult to access)
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10
Q

How much of the weight of a fed liver does glycogen make up?

A

10%

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11
Q

What is the role of glucokinase enzyme?

A
  • Same as hexokinase
  • Converts glucose to glucose-6-phosphate
  • Required because will continue to generate glucose-6-phosphate without negative feedback affecting it
  • Glucose-6-phosphate can enter PPP
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12
Q

What enzyme converts glucose-6-phosphate to glucose-1-phosphate?

A

Phosphoglucomutase enzyme

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13
Q

What enzyme catalyses this reaction?

UTP (uridine triphosphate) + glucose –> UDP-glucose +PPi

A

UDP-glucose pyrophosphorylase

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14
Q

What is UDP?

A
  • Uridine diphosphate acts as glucose carrier

- Extends glycogen chain

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15
Q

What enzyme draws glucose into glycogen?

A
  • Regulatory glycogen synthase

- Stimulated by insulin

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16
Q

What enzyme creates 1,6 glycosidic bonds for glycogen branching?

A

Branching enzyme

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17
Q

Which enzyme does glucagon inhibit in glycogenolysis and what does this prevent?

A
  • Glycogen synthase enzyme

- Prevents UDP-glucose being inserted into glycogen

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18
Q

What enzyme breaks 1,6 glycosidic bonds?

A
  • De-branching enzyme

- Transposes it to back bone

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19
Q

What enzyme breaks down 1,4 glycosidic bonds?

A
  • Glycogen phosphorylase enzyme

- Adds phosphate which destabilises bond causing it to break

20
Q

What enzyme catalyses the reaction glucose-1-phosphate –> glucose-6-phosphate?

A

Phosphoglucomutase

21
Q

What enzyme catalyses the reaction glucose-6-phosphate –> glucose?

A

Glucose-6-phosphatase

22
Q

What is the difference between glucokinase and hexokinase?

A
  • Both convert glucose into glucose-6-phosphate
  • Glucokinase not inhibited by high levels of glucose-6-phosphate
  • Hexokinase activity slows down
  • In liver, high glucoknase levels, glucose-6-phosphate levels rise after meal
  • Forces glucose into all major pathways of glycolysis, PPP and glycogenesis
23
Q

How is glycogenesis regulated?

A
  • Insulin released after meal from β cells in pancreatic islets of Langerhans
  • Bind to RTK
24
Q

What are the functions of insulin?

A
  • Reverse glucagon by deactivating glycogen phosphorylase and activating glycogen
  • -> Also inhibits breakdown of stored fat
  • Promotes expression of glucose transporters on cell surface and subsequent glucose uptake by cells
25
Q

What does glucagon do in the liver?

A
  • Mobilises hepatic glycogen

- Initially through binding to its GPCR

26
Q

What does adrenalin do in the liver?

A
  • Mobilises hepatic or muscle β-adrenergic receptor
27
Q

Which hormones activate adenylyl cyclase?

A

Glucagon and adrenaline

28
Q

What does the activation of adenylyl cyclase lead to?

A
  • Generates cAMP that activates protein kinase A

- When cAMP binds and dissociates its inhibitory subunit

29
Q

What does PKA do in regulating glycogenolysis?

A
  • Directly inhibits glycogen synthase (Reduces glycogenesis)

- Indirectly activates glycogen phosphorylase (increasing glycogenolysis)

30
Q

What does phosphodiesterase enzyme do in the cell?

A
  • Hydrolyses cAMP to AMP permitting inhibitory subunits to re-associate and deactivate PKA
31
Q

Describe glycogen storage in muscle cells

A
  • No glucagon receptor
  • No glucose-6-phosphate
  • Muscle glycogen cannot be accessed to replenish blood glucose
32
Q

How can muscle cells signal for glycogen degradation?

A

Non-hormonally

  • Calcium influx (after nerve stimulation) can activate glycogen phosphorylase- glycogenolysis
  • Strenuous muscle activity leads to accumulation of AMP in muscle cells- increase in AMP conc may activate phosphorylase
33
Q

What are the three types of glycogen storage diseases?

A
  • GSD Type 1 (glucose-6-phosphatase enzyme does not function properly)
  • GSD Type 1B (dysfunctional glucose-6-phosphate transporter)
  • GSD Type 2 (lysosome glycogen problem)
34
Q

Describe GSD Type 1A

A
  • Von Gerke’s Disease
  • Autosomal recessive, gene expression for G6Pase absent
  • Fasting hypoglycaemia- lack of glucose production
  • Accumulation of glycogen in liver and kidney
  • Organomegaly- massive hepatomegaly
35
Q

Describe GSD Type 2

A
  • Pompe’s disease
  • Progressive and multi systemic
  • Skeletal/respiratory/cardiac muscles
  • Autosomal recessive
  • Lysosomal enzyme deficiency of acid maltase (acid alpha glucosidase/GAA)
  • Accumulation of stored glycogen
36
Q

What does alpha glucosidase (GAA) do?

A
  • Catalyses hydrolysis of α-1,4 and 1,6 glycosidic bonds in the lysosome
37
Q

When does gluconeogenesis occur?

A
  • Not in fed state

- Basal state when glycogen stores are depleted

38
Q

What are the different sources of substrates for gluconeogenesis?

A
  • RBC- carbon from lactate
  • Glycerol from fat in adipose tissue
  • Amino acids from muscle tissue
39
Q

What is the only place where new glucose can be made?

A

Liver

40
Q

What are lactate and amino acids converted to in gluconeogenesis?

A
  • pyruvate
41
Q

What enzyme converts pyruvate to oxaloacetate?

A
  • Pyruvate carboxylase
42
Q

What enzyme converts oxaloacetate to phosphoenolpyruvate?

A

PEP carboxykinase

43
Q

What are the two ways to form fructose-1,6-bisphosphate?

A
  • Phosphoenolpyruvate–> Glyceraldehyde-3-phosphate–> fructose-1,6-bisphosphate
  • Glycerol –> dihydroxyacetone-P –> fructose-1,6-bisphosphate
44
Q

What enzyme converts fructose-1,6-bisphosphate to fructose-6-phosphate?

A

Fructose bisphosphate

45
Q

What are the final steps of gluconeogenesis (from fructose-6-phosphate)

A
  • Fructose-6-phosphate –> glucose-6-phosphate

- Glucose-6-phosphate –> glucose

46
Q

What enzyme converts glucose-6-phosphate to glucose?

A

Glucose-6-phosphatase

Metabolism (9 decks)

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