S2 Glycogen and Fat as Energy Storage

Question 1

Which tissues have an absolute requirement for glucose as an energy source?

Answer 1

1. Red blood cells
2. Neutrophils
3. Innermost cells of the kidney medulla
4. Lens of the eye

Question 2

What are the two main energy stores?

Answer 2

Glycogen and fat

Question 3

What is glycogen stored in in skeletal muscles and the liver?

Answer 3

In granules

• in skeletal muscle glycogen is stored intramyofibrillar and intermyofibrillar
• in the liver stored in granules in the hepatocytes

Question 4

What is the structure of glycogen?

Answer 4

It’s a branched polymer consisting of glucose residues.

Residues linked by alpha 1-4 glycosidic bonds and alpha 1-6 glycosidic bonds forming at branch points every 8-10 residues

Question 5

What are the steps in glycogenesis?

Answer 5

1. Glucose + ATP —> glucose-6-phosphate + ADP (hexokinase)
2. Glucose-6-phosphate glucose-1-phosphate (phosphoglucomutase)
3. Glucose-1-phosphate + UTP + H20 —> UDP-glucose + PPi (G1P uridyltransferase)
4. Glycogen(n residues) + UDP-glucose —> glycogen(n+1 residues) + UDP (glycogen synthase and branching enzyme)

Question 6

What is the difference between glycogen synthase and branching enzyme?

Answer 6

Glycogen synthase - alpha 1-4 glycosidic bonds

Branching enzyme - alpha 1-6 glycosidic bonds

Question 7

Does the synthesis of glycogen require energy?

Answer 7

Yes

Question 8

What are the two steps in glycogenolysis?

Answer 8

1. Glycogen(n residues) + Pi —> glucose-1-phosphate + glycogen(n-1 residues) (glycogen phosphorylase or de-branching enzyme)
2. Glucose-1-phosphate glucose-6-phosphate (phosphoglucomutase)

Question 9

What happens to the glucose-6-phosphate in glycogenolysis? (In skeletal muscles and liver)

Answer 9

• muscle - goes into glycolysis - used by muscles for energy production
• liver - goes on to produce glucose - released by the liver into the blood for use by other tissues

Question 10

What enzyme does the liver have that converts glucose-6-phosphate into glucose?

Answer 10

Glucose-6-phosphatase

Question 11

How is liver glycogen metabolism regulated?

Answer 11

• glucagon and adrenaline phosphorylate glycogen synthase leading to a decrease in enzyme activity and glycogen phosphorylase increasing its activity
• insulin de-phosphorylates glycogen synthase and increases its activity and glycogen phosphorylase to decrease the enzyme activity

Question 12

What is an allosteric activator of glycogen phosphorylase in muscles?

Answer 12

AMP

Question 13

What is gluconeogenesis? Where does it occur? What are the main precursors?

Answer 13

When glycogen stores start to deplete alternative sources of glucose is required.

The liver (and a little in the kidney cortex)

Lactate, glycerol and amino acids

Question 14

What are the 3 key enzymes in gluconeogenesis?

Why are these the key enzymes?

Answer 14

1. Phosphoenolpyruvate carboxykinase (PEPCK) - Oxaloacetate to phosphoenolpyruvate
2. Fructose-1,6-bisphosphatase- fructose-1,6-bisphosphate to fructose-6-phosphate
3. Glucose-6-phosphatase- glucose-6-phosphate to glucose

These are the enzymes involved in the irreversible reactions

Question 15

How and why is gluconeogenesis regulated?

Answer 15

PEPCK and fructose-1,6-bisphosphate are regulated by hormones in response to starving/fasting, prolonged exercise and stress.

Glucagon and Cortisol stimulate PEPCK and F-1,6-BP
Insulin inhibits PEPCK and F-1,6-BP

Question 16

What is the time course for glucose utilisation?

Answer 16

1. Glucose from food is utilised in 2 hours
2. Glucose from glycogenolysis is utilised up to 8-10 hours
3. Glucose from gluconeogenesis is utilised from 8-10 hours onwards

Question 17

Which storage of energy is better, triacylglycerol or glycogen?

Answer 17

Triacylglycerol because it store more energy per gram

Question 18

Are TAGs hydrophobic or hydrophilic? What does this mean for its storage?

Answer 18

Hydrophobic

Stored in an anhydrous form in adipose tissue

Question 19

What type of regulation controls storage and mobilisation of TAGs?

Answer 19

Hormonal control

Question 20

What are the steps in triacylglycerol metabolism?

Answer 20

1. TAG is broken down by pancreatic lipase into fatty acids and glycerol in the s. intestine
2. The fatty acids and glycerol are transported into the intestinal epithelial cell and are then packaged into a chylomicron
3. The chylomicrons are transported into the lymph and into the blood (enters blood stream through left subclavian vein)
4. In the blood, the TAG either goes straight to tissues or to adipose tissue. It is stored in adipose tissue where activation, by glucagon and adrenaline, of hormone sensitive lipase causes the transport of fatty acids from the breakdown of TAG in the adipose with albumin occurs to the tissues. At the tissues TAG is mobilised and fatty acid oxidation occurs which releases energy

Question 21

What is lipogenesis? Where does it mainly occur?

Answer 21

Fatty acid synthesis

In the liver

Question 22

What are the stages of lipogenesis?

Answer 22

1. Glycolysis occurs producing pyruvate which enters the mitochondria
2. In the mitochondria, pyruvate forms acetyl-CoA, oxaloacetate which then goes on to form citrate
3. The cent rate is transported to the cytoplasm where it is cleaved to reproduce acetyl-CoA and oxaloaceteate
4. Acetyl-CoA carboxylase produced malonyl-CoA from acetyl-CoA
5. Fatty acid synthase complex builds the fatty acid by sequential addition of 2 carbon units provided by malonyl-CoA (carbon dioxide is lost)
6. The fatty acid and glycerol-3-P form TAG and the TAG is transported by VLDL

Question 23

What is lipolysis?

Answer 23

Fat mobilisation

Glucagon and adrenaline activate hormone sensitive lipase by phosphorylation

Insulin inhibits hormone sensitive lipase by de-phosphorylation

Hormone sensitive lipase breaks down TAG releasing glycerol and free fatty acid into the blood

The fatty acid undergoes beta oxidation and the glycerol is utilised in the liver for gluconeogenesis

Question 24

Where does fatty acid oxidation and fatty acid synthesis occur?

Answer 24

Oxidation - in the mitochondria

Synthesis - in the cytoplasm

Question 25

What coenzymes do fatty acid oxidation and synthesis require?

Answer 25

Oxidation - NAD+ and FADH (oxidative)

Synthesis - NADPH (reductive)