S4) Energy Storage

Question 1

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

Answer 1

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

Question 2

Why are stable blood glucose levels important?

How is this done?

Answer 2

• Essential for normal brain function
• Glycogen stores glucose to enable blood glucose to be kept at required levels

Question 3

How is glycogen stored?

Answer 3

Glycogen is stored as granules

Question 4

Where is glycogen stored?

Answer 4

• Muscle glycogen – stored as granules in and between myofibrils
• Liver glycogen – stored as granules in hepatocyte

Question 5

Describe the molecular structure of glycogen

Answer 5

• Glycogen is a polymer consisting of chains of glucose residues
• Glucose residues linked by α-1-4 glycosidic bonds with α-1-6 glycosidic bonds

Question 6

Glycogenesis is the process of synthesising glycogen. It requires energy.

In four steps, describe this process

Answer 6

⇒ Glucose + ATP → Glucose 6-P + ADP (hexokinase/glucokinase)

⇒ Glucose 6-P → Glucose 1-P (phosphoglucomutase)

⇒ Glucose 1-P + UTP + H₂O → UDP-Glucose + PP_i

⇒ Glycogen_{(n residues)} + UDP-Glucose → Glycogen_{(n + residues)} + UDP (glycogen synthase / branching enzyme)

Question 7

Glycogenolysis is the process of glycogen degradation.

In three steps, describe how this process is not a simple reversal of glycogenesis

Answer 7

⇒ Glycogen_{(n residues)} + P_i → Glucose 1-P + Glycogen_{(n-1 residues)} (glycogen phosphorylase / debranching enzyme)

⇒ Glucose 1-P → Glucose 6-P (phosphoglucomutase)

⇒ Glucose 6-P → released into blood as glucose (liver) / used for glycolysis (muscle)

Question 8

Illustrate and explain how glycogen stores serve different functions in liver and muscle

Answer 8

• Liver: G6P converted to glucose and exported to blood (buffers blood glucose levels)
• Muscle: G6P enters glycolysis for energy production (no glucose-6-phosphatase)

Question 9

Illustrate the relationship between glycogen synthesis and degradation

Answer 9

Question 10

What are the rate limiting enzymes for glycogen metabolism?

Answer 10

• Glycogen synthesis – glycogen synthase
• Glycogen degradation – glycogen phosphorylase

Question 11

Illustrate how the hormonal regulation of glucose metabolism occurs in a reciprocal fashion

Answer 11

Question 12

Explain how the hormonal regulation of muscle glycogen stores differs from that of the liver

Answer 12

• Glucagon has no effect on muscle glycogen stores
• AMP is an allosteric activator of muscle glycogen phosphorylase but not of the liver form of enzyme

Question 13

Glycogen storage diseases are inborn errors of metabolism (inherited diseases).

How do they occur?

Answer 13

Glycogen storage disease arise from deficiency or dysfunction of enzymes of glycogen metabolism

Question 14

Describe three consequences of glycogen storage diseases

Answer 14

• Liver and/or muscle can be affected
• Excess glycogen storage can lead to tissue damage
• Diminished glycogen stores can lead to hypoglycaemia & poor exercise tolerance

Question 15

Identify and describe two examples of glycogen storage diseases

Answer 15

• McArdle disease – muscle glycogen phosphorylase deficiency
• von Gierke’s disease – glucose-6-phosphatase deficiency

Question 16

What is gluconeogenesis and when does it occur?

Answer 16

• Gluconeogenesis is the production of new glucose
• Occurs beyond ~ 8 hours of fasting as liver glycogen stores start to deplete and an alternative source of glucose is require

Question 17

Where does gluconeogenesis occur?

Answer 17

Occurs in liver and to lesser extent in kidney cortex

Question 18

Identify and describe the three major precursors for gluconeogenesis

Answer 18

• Lactate – from anaerobic glycolysis in exercising muscle and red blood cells (Cori cycle)
• Glycerol – released from adipose tissue breakdown of triglycerides
• Amino acids – mainly alanine

Question 19

Describe the Cori Cycle

Answer 19

Question 20

Why can glucose not be synthesised from acetyl-CoA?

Answer 20

Acetyl-CoA cannot be converted into pyruvate as PDH reaction is irreversible so there is no net synthesis of glucose from acetyl-CoA

Question 21

Identify the three key enzymes in gluconeogenesis

Answer 21

Steps 1 & 2 are the major control sites of pathway

Question 22

Which enzymes are used in the hormonal regulation of gluconeogenesis?

Answer 22

• Phosphoenolpyruvate carboxykinase (PEPCK)
• Fructose 1,6-bisphosphatase

Question 23

Gluconeogenesis is regulated by hormones in response to which physiological states?

Answer 23

• Starvation/fasting
• Prolonged exercise
• Stress

Question 24

Illustrate how the hormonal regulation of gluconeogenesis is dependent on the enzymes PEPCK and Fructose 1,6-bisphosphatase

Answer 24

Question 25

Outline the time course of glucose utilisation

Answer 25

Question 26

How and when are lipids stored?

Answer 26

- TAG is storaged when lipid intake is in **excess of requirements** - TAGs are hydrophobic and therefore stored in an **anhydrous form in adipose tissue**

Question 27

The storage & mobilisation of TAGs is under hormonal control. When are TAGs utilised?

Answer 27

- Prolonged exercise - Stress - Starvation - Pregnancy

Question 28

TAGs are stored in adipocytes in adipose tissue. Describe the structure and contents of these cells

Answer 28

Question 29

Provide a brief overview of dietary triacylglycerol metabolism

Answer 29

Question 30

In six steps, outline the mechanism of lipogenesis

Answer 30

⇒ Glucose → **pyruvate** in cytoplasm (glycolysis) ⇒ Pyruvate enters mitochondria and forms **acetyl-CoA & OAA** ⇒ Acetyl-CoA and OAA condense to form **citrate** ⇒ Citrate enters cytoplasm and cleaved back **Acetyl-CoA & OAA** ⇒ **Acetyl-CoA carboxylase** produces malonyl-CoA from Acetyl-CoA ⇒ **Fatty acid synthase complex** builds fatty acids by sequential addition of 2C by malonyl-CoA

Question 31

What is the key regulatory enzyme in lipogenesis?

Answer 31

Acetyl-CoA carboxylase

Question 32

Describe the hormonal regulation of Acetyl CoA carboxylase

Answer 32

- **Insulin** (covalent de-phosphorylation), & citrate (allosteric) increase activity - **Glucagon/adrenaline** (covalent phosphorylation) & AMP (allosteric) decrease activity

Question 33

Compare and contrast fatty acid synthesis and β oxidation

Answer 33

Question 34

Fat mobilisation occurs in the adipose tissue and is under hormonal regulation by lipase. Illustrate the mechanism of lipolysis

Answer 34