Carbohydrate metabolsim

Question 1

What is the critical blood glucose level?

Answer 1

2.5mM

Question 2

What are the symptoms of hypoglycaemia?

Answer 2

• Muscle weakness
• Loss of coordination
• Mental confusion
• Sweating
Hypoglycaemic coma and death

Question 3

What can hyperglycaemia lead to?

Answer 3

It can lead to non enzymatic modification of proteins:
  Cataracts
  Modification to lipoproteins 
  which is important in 
  atherosclerosis
  Hyperosmolar coma

Question 4

What synthesis does excess blood glucose lead to ?

Answer 4

• Glycogen synthesis
• Pentose phosphate synthesis
Fatty acid synthesis

Question 5

What does a lack of blood glucose lead to?

Answer 5

• Glycogen breakdown

* Gluconeogenesis

Question 6

What does the liver mainly store?

Answer 6

Main storage of excess glucose

Question 7

What is glucose phosphorylated by?

Answer 7

Glucose phosphorylated by glucokinase and traps glucose in the cell

Question 8

What is excess glucose synthesised into?

Answer 8

Excess glucose is synthesised into glycogen which is branched and compact.

Question 9

Why isn’t glucose just stored as glucose in cells?

Answer 9

Glucose itself is too osmotically active causing an osmotic effect that draw in water and damages the cell.

Question 10

What are the steps for glycogen synthesis?

Answer 10

• G6P converted to Glucose 1 phosphate by phosphoglucomutase
• G1P activated by UTP forming UDP-glucose
• UDP glucose binds to glycogenin to start glycogen synthesis
Alpha 1-6 bonds formed at the 11th residue

Question 11

Why is glucose stored as glycogen?

Answer 11

• Cannot store glucose as its osmotically driven
• 400mM glucose is stored as 0.01 mM glycogen
• Fats can’t be mobilised as readily
• Fat cannot be used as an energy source in the absence of oxygen
Fats cannot be converted in to glucose

Question 12

What are the 2 products formed from the breakdown of glycogen and which is the major product?

Answer 12

Glucose 1 phosphate and glucose

Glucose 1 phosphate is the major product

Question 13

What is glycogen phosphorylase?

Answer 13

Key enzyme in glycogenolysis and its activity forms glucose-1-phosphate

Question 14

What does glycogen phosphorylase break?

Answer 14

Breaks the 1-4 link

Question 15

What is the structure of glycogen phosphorylase and how is this advantageous?

Answer 15

§ Many phosphorylase molecules are bound to each glycogen particle:
Therefore glycogenolysis can be switched on rapidly

Question 16

What is ultimately formed and what does this provide?

Answer 16

G6P ultimately formed provides fuel for working muscles

Question 17

What happens to G6P in the liver and what is the level maintained?

Answer 17

In liver, G6P is de-phosphorylated and secreted into the blood, maintaining 5 mmol/l blood sugar

Question 18

What type of enzyme is glycogen phosphorylase and how is it regulated?

Answer 18

An allosteric enzyme which is activated by phosphorylation but modulated by other factors

Question 19

What type of enzyme is translocase?

Answer 19

De-branching enzyme

Question 20

What are the two activities associated with glycogen phosphorylase?

Answer 20

□ Transferase activity moves the last glucose residues to the non-reducing end of the existing chain

Glucosidase that removes the 1-6 link releasing glucose

Question 21

How can glycogen phosphorylase b activated in muscles?

Answer 21

In muscle, glycogen phosphorylase b can be activated by 5’-AMP without being phosphorylated

Question 22

How does 5’AMP form?

Answer 22

5’-AMP forms when ATP is depleted

Question 23

What does ATP do at the binding site of glycogen phosphorylase?

Answer 23

ATP binds to the same site and blocks activation

Question 24

What else blocks 5’AMP activation?

Answer 24

G6P also blocks 5’-AMP activation

Question 25

What inhibits activated phosphorylase a in the liver?

Answer 25

In the liver the activated phosphorylase a is inhibited by glucose

Question 26

What activates phosphorylase b kinase ?

Answer 26

Ca2+ activate phosphorylase b kinase

Question 27

What does Ca2+ in muscles mediate?

Answer 27

In muscle, mediating glycogenolysis during muscle contraction

Question 28

When is their maximum activity in muscles?

Answer 28

Max activity with Ca2+ and phosphorylation

Question 29

How is Ca2+ release stimulated in the liver?

Answer 29

In liver, α-adrenergic activation stimulates Ca2+ release

Question 30

When is glycogen synthase activated?

Answer 30

Activated in times of plenty of glucose

Question 31

What activates glycogen synthase?

Answer 31

Activated by ATP and G6P

Question 32

How is glycogen synthase inactivated?

Answer 32

Inactivation by phosphorylation by protein Kinase A

Question 33

How is glycogen synthase activated?

Answer 33

Activated by dephosphorylation by protein phosphatase-1

Question 34

When is glycogen phosphorylase activated?

Answer 34

Activated when glucose in short supply

Question 35

What is glycogen phosphorylase inactivated by?

Answer 35

Inactivated by ATP and G6P

Question 36

How is glycogen phosphorylase activated?

Answer 36

Activated by phosphorylation by phosphorylase kinase A

Question 37

How is glycogen phosphorylase inactivated?

Answer 37

Inactivated by dephosphorylation by protein phosphatase-1

Question 38

When is the pentose phosphate pathway activated?

Answer 38

Activated when plenty of glucose is present

Question 39

Why is the pentose phosphate pathway important and why?

Answer 39

• Important for generating ribose 5 phosphate | Important precursor for component of DNA and RNA and also important for coenzymes the body needs

Question 40

What does the pentose phosphate pathway generate when excess glucose is present?

Answer 40

Pathway generates NADPH which is required for fatty acid synthesis

Question 41

What can ribose 5 phosphate be converted back into in pentose phosphate pathway?

Answer 41

Ribose 5 phosphate can be converted back to G6P

Question 42

What is gluconeogenesis?

Answer 42

When glucose is produced from non-carb sources at low glucose levels

Question 43

Why is blood glucose maintained?

Answer 43

• Blood glucose maintained as it is the preferred fuel for the brain and only fuel for red blood cells

Question 44

What are the daily requirements of the body in terms of glucose?

Answer 44

Daily requirement 160g

Question 45

How much glucose does the brain require?

Answer 45

120g

Question 46

What are the total body reserves?

Answer 46

210g

Question 47

What does the glucogenic pathway convert?

Answer 47

Gluconeogenic pathway converts pyruvate to glucose

Question 48

Where does gluconeogensis mostly take place?

Answer 48

Mostly takes place in the liver and a little in the kidney, however during starvation, kidney production rises to 40%

Question 49

What are the 3 most important substrates for gluconeogenesis?

Answer 49

○ Alanine ○ Lactate Glycerol

Question 50

What are the steps involved in gluconeogenesis?

Answer 50

1. Pyruvate caboxylase which converts pyruvate to oxaloacetic acid which is then converted into phosphoenol pyruvate by phosphoenol pyruvate carboxykinase. 2. 3 C converted to G6P by fructose biphosphatase which is then converted to glucose by glucose 6 phosphotase

Question 51

Another way for glucose to be synthesised

Answer 51

Glycerol can be used to synthesise glucose from the backbone of fatty acids

Question 52

Where is oxaloacetic acid generated?

Answer 52

Oxaloacetic acid from pyruvate is generated in the mitochondria

Question 53

Where is pyruvate synthesised?

Answer 53

Pyruvate is synthesised in the cytosol

Question 54

How is phosphoneol pyruvate synthesised?

Answer 54

○ Pyruvate transported to mitochondria from cytosol ○ Then converted to oxaloacetate by pyruvate carboxylase which cannot exit the mitochondria Therefore converted to malate which is then transported out back to the cytosol where its converted to oxaloacetate and then phosphoneol pyruvate.

Question 55

Why is pyruvate first transported to the mitochondria in the synthesis of phosphoneol pyruvate?

Answer 55

Because the enzymes required for the production of oxaloacetate are present inside the mitochondria