Lecture 3- Glycogen And Lipid Storage

Question 1

What tissues have an absolute glucose requirement?

Answer 1

Red blood cells
Lens of eye
Neutrophils
Innermost cells of kidney medulla

Stable glucose level absolute requirement for brain function

Question 2

What is normal blood glucose?

Answer 2

5mmol/L which will increase for a short period after eating.

Question 3

What is the clinical consequence of having over 8mmol/L glucose over a prolonged period?

Answer 3

Any more glucose that this cannot be absorbed and will be excreted in the urine. Having this elevated level of blood glucose for prolonged periods leads to many of the undesirable effects associated with diabetes

Question 4

What problems can prolonged elevated plasma glucose cause?

Answer 4

Neuropathy, poor microvasculature and these combined mean that foot damage can be hard to detect and then hard to repair

Question 5

At what blood glucose level will you suffer brain damage and probable death?

Answer 5

0.6mmol/L

Question 6

Where in the body is glycogen stored and how is it used?

Answer 6

300g muscle used for energy

100g liver used to maintain plasma glucose levels

Question 7

How is glycogen structured?

Answer 7

A highly branched polymer with alpha 1-4 bonds and alpha 1-6 bonds which result in branching. Dimer of the protein glycogenin acts as a primer in the centre

Question 8

Why is glycogen highly branched?

Answer 8

Osmotically inactive in the form and provides lots of points for glucose releasing enzymes to act on

Question 9

What happens in glycogenesis or glycogen synthesis?

Answer 9

Energy is used to form UDP-glucose which is added to glycogen molecule through either glycogen synthase which makes the alpha 1-4 glycosidic bonds or branching enzyme which makes the alpha 1-6 glycosidic bonds

Question 10

What happens in glycogenolysis

Answer 10

Glycogen is acted on by glycogen phosphorylase and de-branching enzyme to ultimately make glucose 6 phosphate to be used by muscle or glucose to be released into blood by the liver

Question 11

Are glycogenolysis and glycogenesis the revers of each other?

Answer 11

No, they use different enzymes which allows for simultaneous inhibition of one pathway and stimulation of the other.

If enzymes weren’t different both pathways would have to run at the same time.

Question 12

What enzymes are primarily responsible for glycogen synthesis and breakdown?

Answer 12

Glycogen synthase and glycogen phosphorylase

Question 13

Effect of glucagon and adrenaline on glycogen?

Answer 13

Cause the phosphorylation of glycogen synthase which inhibits it and the phosphorylation of glycogen phosphorylase which activates it.

Question 14

Effect of insulin on glycogen synthesis?

Answer 14

De phosphorylase glycogen synthase which activates it and de phosphorylase glycogen phosphorylase which deactivates it

Question 15

What acts as an allosteric activator for muscle glycogen phosphorylase but not the liver enzyme?

Answer 15

AMP (low energy need breakdown of glycogen)

Question 16

Effect of glucagon on muscle glycogen stores?

Answer 16

Has no effect

Question 17

Glycogen storage disease examples?

Answer 17

Von Gierke’s disease- glucose 6 phosphate deficiency results in liver glycogen not being mobilised and enlargement of the liver can result

McArdle’s disease-

Muscle glycogen phosphorylase deficiency which results in tired muscles as cant mobilise glycogen

Question 18

What happens in gluconeogenesis?

Answer 18

Beyond 8 hours of fasting it kicks in. It uses glycerol, lactate and amino acids to make glucose and it occurs in the liver and kidney to a small degree

Question 19

Can acetyl Co-A be used in gluconeogenesis?

Answer 19

No as the reaction that created acetyl Co-A using the enzyme pyruvate dehydrogenase is irreversible

Question 20

Gluconeogenesis enzymes?

Answer 20

Some different to glycolysis. Phosphoenolpyruvate carboxykinas (PEPCK), fructose 1,6-bisphosphatase and glucose-6-phosphatase are the key enzymes

Insulin inhibits while cortisol and glucagon stimulate

Question 21

What are the two key regulatory enzymes of glycolysis?

Answer 21

Phosphoenolpyruvate carboxykinas (PEPCK) and fructose 1,6-bisphosphatase which are activated and inhibited by glucagon/ cortisol and insulin respectively

Question 22

Time course of glucose utilisation?

Answer 22

Glucose from food up to 2 hours

Glycogenolysis for next 8-10 hours

Gluconeogenesis another 10 hours

Question 23

What is triacylglycerol?

Answer 23

Three fatty acids and a glycerol

Question 24

Why are triacylglycerols stored in adipose tissue?

Answer 24

Because they are hydrophobic

Question 25

When is triacylglycerol utilised?

Answer 25

During prolonged exercise, periods of stress, pregnancy and starvation

Question 26

What controls the storage and mobilisation of TAGs?

Answer 26

Hormones

Question 27

What is an adipocyte?

Answer 27

Large lipid droplet consisting of triacylglycerol and cholesterol ester and cytoplasm and organelles pushed to the edge

Question 28

Why once you become obese is it very hard to keep weight off?

Answer 28

Because once existing adipocytes are filled in obesity more are generated which will always look to be filled

Question 29

Describe triacylglycerol metabolism?

Answer 29

Triacylglycerol split into glycerol and fatty acids in the small intestine by pancreatic lipase. Fatty acids and glycerol taken into intestinal epithelial cell where they recombine to form TAG and are taken up by a chylomicron (lipoprotein). The chylomicron travels through the lymph to the right subclavian vein where the TAG can be transported for adipose storage or to tissues for fatty acid oxidation. Hormone sensitive lipase is sensitive to glucagon/adrenaline and insulin

Question 30

What regulates triacylglycerol metabolism?

Answer 30

Insulin will inhibit hormone sensitive lipase while glucagon/adrenaline will activate it leading to TAG mobilisation

Question 31

What cant use TAG for energy?

Answer 31

Glucose dependent organs and the brain as fatty acid cant pass the blood brain barrier

Need mitochondria for beta oxidation

Question 32

Lipogenesis (fatty acid synthesis)?

Answer 32

Occurs mainly in the liver. Glucose turned to pyruvate. Pyruvate becomes acetyl Co-A which is turned into malonyl Co-A by acetyl-CoA carboxylase and then fatty acid synthase complex builds fatty acids by adding two carbon units from malonyl Co-A. Requires ATP and NADPH.

Question 33

Which lipoprotein transports dietary fat and which transports synthesised fat?

Answer 33

Dietary= chylomicrons

Synthetic= VLDLs

Question 34

What is the breakdown of fatty acids known as?

Answer 34

Beta oxidation

Question 35

Why is fatty acid synthesis not the reverse of lipolysis?

Answer 35

Allows greater flexibility as intermediates and substrates can be different

Better control (can operate independently or at the same time)

Thermodynamically irreversible steps can be by-passed