S18) Energy Production III — Lipids, β-Oxidation & Ketone Bodies

Question 1

Identify and describe the three different classes of lipids

Answer 1

• Fatty acid derivatives – fatty acids and triacylglycerol
• Hydroxy-methyl-glutaric acid derivatives – ketone bodies, cholesterol
• Vitamins – ADEK

Question 2

Explain how energy storage varies between a healthy and obese man

Answer 2

Question 3

Describe the structure of triacyglycerol

Answer 3

Triacylglycerols are hydrophobic

Question 4

Describe the storage of TAG

Answer 4

• Stored in an anhydrous form
• Stored in adipose tissue
• Storage / mobilisation under hormonal control

Question 5

Identify three circumstances where triacylglycerols are used

Answer 5

• Prolonged exercise
• Starvation
• Pregnancy

Question 6

Identify the tissues involved in triglyceride metabolism and illustrate their role

Answer 6

Question 7

Where does stage 1 of TAG metabolism occur?

Answer 7

Gastrointestinal tract (extracellular)

Question 8

What occurs in stage 1 of TAG metabolism?

Answer 8

• Extracellular hydrolysis of dietary lipids (TAG) in small intestine by pancreatic lipases
• Fatty acids and glycerol are formed

Question 9

In 5 steps, describe what happens in TAG metabolism after absorption int the GI tract

Answer 9

⇒ Converted back to triglycerides in GI tract

⇒ Packaged into lipoprotein particle (chylomicrons)

⇒ Released into circulation via lymphatics

⇒ Carried to adipose tissue

⇒ Stored as triglyceride

Question 10

Describe fat mobilisation

Answer 10

• Fatty acids are released when needed
• They are carried to tissues as albumin-fatty acid complex

Question 11

Fat mobilisation is under hormonal control.

Describe this

Answer 11

Hormone-sensitive lipase:

• Increases with glucagon/adrenaline
• Decreases with insulin

Question 12

Which consumer tissues are fatty acids not mobilised to?

Answer 12

• Cells without mitochondria e.g. RBC
• Brain; fatty acids do not easily pass blood-brain barrier

Question 13

In 5 steps, describe and illustrate the triglyceride/fatty acid cycle in adipose tissue

Answer 13

1 – Glucose transport

2 – Glycolysis

3 – Esterification

4 – Lysis

5 – Re-esterification

Question 14

What causes the release of fatty acids as alternative fuel?

Answer 14

Low extracellular [glucose]

Question 15

Describe the molecular structure of fatty acids

Answer 15

Amphipathic: contain hydrophilic & hydrophobic groups

Question 16

What are the two types of fatty acids?

Answer 16

• Saturated: no double bonds between neighbouring C-atoms
• Unsaturated: 1/more double bonds between neighbouring C-atoms

Question 17

Where does stage 2 of fatty acid metabolism occur?

Answer 17

Mitochondrion

Question 18

In three steps, describe what occurs in fatty acid catabolism

Answer 18

⇒ FA is activated outside the mitochondrion

⇒ FA is transported across the inner mitochondrial membrane using a carnitine shuttle

⇒ FA cycles through sequence of oxidative reactions, with C₂ removed each cycle

Question 19

Fatty acid activation occurs outside the mitochondria, in the cytoplasm.

Describe how this occurs

Answer 19

• Activated by linking to coenzyme A by the action of fatty acyl CoA synthase
• Activated fatty acids (fatty acyl~CoA) do not readily cross the inner mitochondrial membrane (carnitine shuttle)

Question 20

Carnitine shuttle transports fatty acyl~CoA across the mitochondrial membrane.

Describe how and why this process is regulated

Answer 20

• Regulated, so controls the rate of FA oxidation
• Inhibited by malonyl~CoA (biosynthetic intermediate)

Question 21

Fatty acid catabolism is also called β oxidation.

Identify three key features of this process

Answer 21

• H⁺ and e^- transferred to NAD⁺ and FAD
• Stops in absence of O₂
• No ATP synthesis

Question 22

Briefly describe glycerol metabolism

Answer 22

Glycerol can be transported in the blood to the liver, where it is metabolised

Question 23

Acetyl-CoA the main convergence point for catabolic pathways.

What is its function?

Answer 23

Acetyl~CoA is the most important intermediate in both catabolic and anabolic pathways

Question 24

Three ketone bodies produced in the body.

What are they?

Answer 24

• Acetoacetate: CH₃COCH₂COO^- (liver)
• Acetone: CH₃COCH₃
• β-hydroxybutyrate: CH₃CHOHCH₂COO^- (liver)

Question 25

Describe the physiological and pathological variation in the plasma concentration of ketone bodies

Answer 25

- **Normal** \< 1 mM - **Starvation** = 2-10 mM (physiological ketosis) - **Untreated Type 1 diabetes** \> 10 mM (pathological ketosis)

Question 26

Briefly outline the pathways in which ketone bodies are synthesised by liver mitochondria

Answer 26

Question 27

How is acetone formed?

Answer 27

**Acetone** is formed from the spontaneous (non-enzymatic) decarboxylation of acetoacetate

Question 28

Explain how ketone body production is controlled in the liver

Answer 28

Question 29

Outline the pathways involved in ketone metabolism

Answer 29

Question 30

Explain how ketone bodies synthesis is regulated by the insulin:glucagon ratio in fed and starvation states

Answer 30

- **Fed state:** high insulin:glucagon inhibits lyase and activates reductase → cholesterol synthesis - **Starvation state:** low insulin:glucagon inhibits reductase and activates lyase → ketone body synthesis

Question 31

Illustrate how ketone bodies spare glucose in early starvation/diabetes

Answer 31

Question 32

Illustrate how ketone bodies spare glucose in late starvation/diabetes

Answer 32

Question 33

How are excess ketone bodies excreted from the body?

Answer 33

Above renal threshold, excreted in urine (**ketonuria**)

Question 34

How is acetone excreted from the body?

Answer 34

Volatile acetone may be **excreted via the lungs** (characteristic smell of acetone on breath)