Lecture 3- Energy storage (glycogen)

Question 1

which tissues have an absolute requirment for glucose as an energy source

Answer 1

• RBC
• Neutrophils- resp burst
• Innermost cells of kidney medulla- blood supply low because so deep
• Lens of the eye- not very rich blood supply (oxidative phos limited)

Question 2

brain’s energy source

Answer 2

• Stable BG essential for normal brain function
• Brain has a requirement for glucose
• Can use ketones but takes a while to adapt

Question 3

normal BG

Answer 3

5mmol

Question 4

To enable bg to be kept at stable levels glucose is stored as

Answer 4

glycogen

Question 5

consequence of hypoglycaemia (2.8 mmol/L)

Answer 5

confusion

Question 6

consequence of hypoglycaemia (1.7 mmol/l)

Answer 6

weakness and nausea

Question 7

consequence of hypoglycaemia (1.1 mmol/l)

Answer 7

muscle cramps

Question 8

consequence of hypoglycaemia (0.6 mmol/l)

Answer 8

brain damage and death

Question 9

glycogen is stored as ……….. in the ….. and ……

Answer 9

• Glycogen is stored as granules
• Muscle
• Liver

Question 10

glycogen in muscle

Answer 10

Distinction between intra and intermyofibrillar glycogen

Glycogen in muscle= for muscle contraction

Question 11

how is glycogen stored in the liver

Answer 11

Glycogen stored as granules in hepatocytes

Glycogen store in liver= buffers plasma glucose levels

Question 12

examples of conditions which cause hypoglycaemia

Answer 12

• e.g. diabetic patient which has taken insulin injections and forgotten to eat meal
• e.g. Someone with acute alcoholic poisoning
• e.g. Athlete which has pushed themselves over the limit

Question 13

see the effects of hypoglycaemia if the bg drops to

Answer 13

2.8 mmol/l

Question 14

structure of glucogen

Answer 14

• Glycogen is a polymer consisting of chains of glucose residues
• Chains are organised like the branches of a tree originating from a dimer of the protein glycogenin (acts as a primer at core of glycogen structure)
• Glucose residues linked by alpha1-4 glyosidic bonds with alpha 1-6 glyosidic bonds forming branch points every 8-10 residues

Question 15

protein glycogenin

Answer 15

(acts as a primer at core of glycogen structure)

Question 16

why does glycogen have this structure

Answer 16

• Will release glucose quickly
• Reduces the osmotic effect on the cell

Question 17

glycogenesis is the pathway by which

Answer 17

glycogen is synthesised

Question 18

glycogenolysis is the pathway by which

Answer 18

glycogen is degraded to produce glucose or be used in glycolysis

Question 19

synthesis of glycogen requires

Answer 19

Energy (ATP)

Question 20

outline glycogenesis

Answer 20

1. glucose is convert to glucose 6-phosphate by hexokinase
2. glucose 6-phosphate is converted to glucose 1-phosphate by phosphoglucomutase
3. glucose 1 phohate is converted to UDP glucose by G1P uridylyltransferase
4. glycogen (n residues) + UDP-glucose –> glucogen (n +1 + UDP
   
   • glycogen synthase–> alpha 1-4 glycosidic bonds
   • branching enzyme –> alpha 1-6 glycosidic bonds

Question 21

glycogen synthase

Answer 21

enzyme which catalyses the formation of 1-4 glycosidic bonds

Question 22

branching enzyme

Answer 22

enzyme which catalyses the formation of 1-6 glycosidic bonds

Question 23

outline glycogenolysis

Answer 23

1. glycogen (n residues) + Pi –> Glycose 1-phosphate _ glycogen (n-1 residues)
   
   • glycogen phosphorylates or de-branching enzyme
   • glucose 1-phosphate –> glucose 6-phopshate
2. in the muscle glucise 6-phosphate is used by muscle for energy production
3. in the liver glucose-6 phophate is converted to glucose and rleeased into the blood

Question 24

in the muscle glucose 6-phosphate

Answer 24

• is used by muscle for energy production
  *

Question 25

in the liver glucose-6 phophate is converted to

Answer 25

glucose and released into the blood

Question 26

glycogenolysis is not

Answer 26

a simple reversal of glycogenesis

Question 27

function of glycogen storesin the liver

Answer 27

* G6P converted to glucose and exported to the blood * Acts as a buffer of blood glucose levels

Question 28

Function of glycogen stores in the muscle

Answer 28

* Muscle lacks the enzyme glucose-6-phosphatase * G6P enters glycolysis for energy production

Question 29

summary of glycogenolysis and glycogenesis

Answer 29

Question 30

rate limiting enzyme of glycogen synthesis

Answer 30

glycogen synthase

Question 31

rate limiting enzyme of glycogen degradation

Answer 31

glycogen phosphorylase

Question 32

as rate limiting enzymes, glycogen synthase and glycogen phosphorylase are under

Answer 32

hormonal control- mainly to maintain plasma glucose

Question 33

which hromones increase BG and by which mechangism

Answer 33

glucagon and adrenaline **Glycogen synthase** —\> phosphorylation - decrease enzyme activity- increase BG **Glycogen phosphorylase** —\> phosphorylation - increase enzyme activity - increase BG

Question 34

which hormoens decrease blood glucose

Answer 34

insulin ## Footnote **Glycogen synthase**—\> de-phos – increase **Glycogen phosphorylase**—\> de-phos - decrease

Question 35

glucagon has no effect on which cells

Answer 35

muscle - no glucagon receptros ## Footnote AMP is an allosteric activator of muscle glycogen phosphorylase but not of the liver form of the enzyme

Question 36

glycogen storage disease

Answer 36

Inborn error of metabolism (inherited) Deficiency or dysfunction in enzymes involved in glycogen metabolism 12 types

Question 37

in glycogen storage disease liver and /or muscle can be affected

Answer 37

* Excess glycogen storage can lead to tissue damage * Diminished glycogen stores can lead to hypoglycaemia and poor exercise tolerance

Question 38

examples of glycogen storage disease (2)

Answer 38

**von Gierkes disease** - G6P deficiency **McArdle disease** – muscle glycogen phosphorylase deficiency

Question 39

Beyond 8 hours of fasting, liver glycogen stores start to deplete and alternative some of glucose is required......

Answer 39

- gluconeogenesis

Question 40

where does glucoseneogenesis occur

Answer 40

Occurs in liver and to lesser extent in kidney cortex

Question 41

three major precursors of glucoseneogenssi

Answer 41

lactate glycerol amino acids

Question 42

lactate from

Answer 42

anaerobic glycolysis in exercising muscle and red blood cells (**cori cycle)**

Question 43

glycerol

Answer 43

released from adipose tissue breakdown of triglycerides

Question 44

amino acid

Answer 44

mainly alanine

Question 45

why is there no net syn thess from acetyl-coA

Answer 45

acetyl coA cannot be converted into pryuvate (pyruvate dehydreogenase reaction is irreversible)

Question 46

Although similar, the gluconeogenesis pathway is not

Answer 46

simply the opposite of glycolysis Has PEPCK instead of pyruvate kinase

Question 47

Key enzymes of glucoseneogenesis

Answer 47

1) Phosphoenolpyruvate carboxykinase (PEPCK) 2) Fructose 1,6-bisphosphatase 3) Glucose-6- phosphatase

Question 48

Regulation of gluconeogenesis

Answer 48

2 enzymes regulated by hormones in response to: * Starvation/fasting * Prolonged exercise and stress Glucagon and cortisol

Question 49

in response to starvation which hormones are released and what is effect on glucoseneogenesis enzymes

Answer 49

glucagon and cortisol are released - PEPCK - increased amount - fructose 1,6 bisphosphatase - icnreased amount snad activitity **effect- stimulates glyconeogensis**

Question 50

in response to higher BG which hormones are released and what is effect on glucoseneogenesis enzymes

Answer 50

insulin - PEPCK - decreased amounts - Fructose 1,6 bisphosphatase - decreased amkoutn and activity **Effect- inhibits glucoseneogenesis**