Energy Release From Fat

Question 1

1) State 3 biological functions of lipids

Answer 1

• components of cell membranes (phospholipids, cholesterol)
• precursors of hormones (cholesterol -> steroid hormones, arachidonic acid -> prostaglandins)
• long term fuels (triglycerides)

Question 2

2) State 3 factors that make triglycerides an efficient fuel storage

Answer 2

• compact: TG stored as large fat droplets in fat cells of adipose tissue
• large body stores: fat mass is much larger than glucose and glycogen in an adult
  -efficiency on weight basis:
  1g fat = 38kJ
  1g protein = 21kJ
  1g carbohydrate = 17kJ

Question 3

3) Which enzyme is crucial for the breakdown of TGs into fatty acids and glycerol?

Answer 3

(Adipose tissue) TAG/DAG/MAG lipase

[TAG, DAG and MAG all produce fatty acids however the breakdown of MAG also produces glycerol as the final product]

Question 4

4) Define fatty acid metabolism via beta-oxidation and state where it occurs

Answer 4

Beta-oxidation: the biological energy of FA molecule is conserved as the transfer of 2 hydrogen atoms to the cofactors NAD+ and FAD (no direct ATP synthesis)
[a series of 4 enzyme reactions, removing 2C as acetyl CoA]
- Occurs in the mitochondria matrix

Question 5

5) Reaction#1: Removal of two Hydrogen atoms

Answer 5

Acyl-CoA –> Enoyl-CoA (sat –> unsat)

• Loss of 2 H atoms
• Acyl-CoA dehydrogenase
• FAD –> FADH2

Question 6

6) Reaction#2: Addition of water

Answer 6

Enoyl-CoA –> Hydroxyacyl-CoA

- Addition of water

Question 7

7) Reaction#3: Removal of two Hydrogen atoms

Answer 7

Hydroxyacyl-CoA –> beta-ketoacyl-CoA

• loss of 2 H atoms
• hydroxyacyl-CoA dehydrogenase
• NAD+ –> NADH + H+

Question 8

8) Reaction#4: Removal of two carbon units

Answer 8

beta-ketoacyl-CoA –> acetyl CoA

• addition of coenzymeA
• produces fatty acyl-CoA and acetyl CoA

[the shorter FA produces re-enters the reaction cycle to produce more acetyl CoA]

Question 9

9) For a FA of 16C, how many cycles of the beta-oxidation cycle would it go through, and how many molecules of NADH and FADH2 would be produced?

Answer 9

• 7 cycles

- 7 NADH and 7 FADH2

Question 10

10) For a FA of 16C, how many molecules of Acetyl-CoA would be produced?

Answer 10

• 8 molecules

Question 11

11) Where are the long chain fatty acids first activated and describe the reaction that occurs?

Answer 11

• in the cytosol
• LCFA –> fatty acyl-CoA
• addition of Coenzyme A
• fatty acyl-CoA synthetase enzyme
• involves 2 energy rich bonds broken –> favorable
• ATP–> AMP + PPi

Question 12

12) What bonds does CoA form with carboxylic acids?

Answer 12

thioester bonds

Question 13

13) Describe how the fatty acyl-CoA is then transported from the cytosol into the mitochondria

Answer 13

• Reaction: Fatty acyl-CoA + carnitine (outside) -> CoA + RC=O-carnitine (inside)
• Passes through outer mitochondria membrane via Acyl transferase enzyme
  [carnitine shuttle]

Question 14

14) Which enzyme is involved in the transport of RC=O-carnitine from the intermembrane space into the matrix (across the inner mitochondria membrane)?

Answer 14

• Translocase

Question 15

15) Describe how Fatty acyl-CoA is reformed inside the mitochondria

Answer 15

• Reaction: RC=O-carnitine + CoA -> fatty acyl-CoA + carnitine (returns to matrix via translocase to transport more FA across)
• Enzyme: carnitine palmitoyl-transferase II

Question 16

16) State the 3 factors in the regulation of fat metabolism

Answer 16

• release of FA from adipose tissue (adrenaline and glucagon activate lipase, when [glucose] is low)
• rate of entry into mitochondria via carnitine shuttle (high carb intake inhibits carnitine shuttle as fats are synthesised, not broken down)
• rate of reoxidation of cofactors NADH and FADH2 by cytochrome chain (feedback control)

Question 17

17) Describe how odd-numbered carbon chain fatty acids are metabolised

Answer 17

• Beta-oxidation until 3C remains (Acetyl-CoA released at each stage)
• Addition of CO2 and ATP –> ADP + Pi
• involving propionyl-CoA carboxylase
• second reaction involves methylmalonyl-CoA mutase which produces Succinyl-CoA which enters the TCA cycle

Question 18

18) Define and describe the process ketogenesis

Answer 18

• Occurs when fat metabolism is the main source of energy in starvation/ type I diabetes
• FA oxidation in hepatocytes (liver cells) leads to high [Acetyl-CoA] which exceeds TCA cycle capacity
• Excess Acetyl-CoA is converted into ketone bodies in the liver and excreted

Question 19

19) Define ‘ketone bodies’ and what are the forms in which they are excreted?

Answer 19

• Three related compounds produced from fat metabolism, acetoacetate and beta-hydroxybutyrate are released into the bloodstream and are used as a source of energy instead of glucose (in MOST cells) , during fasting, and acetone which is excreted via breath

Question 20

20) Why can ketone bodies not be used as an energy source in the liver?

Answer 20

Liver lacks the enzyme ‘beta-ketoacyl CoA transferase’

[in most cell types, ketone bodies can be converted back into TCA cycle intermediates - succinate and acetyl-CoA]

Question 21

21) Why can the brain and red blood cells not utilise ketone bodies as an energy source?

Answer 21

• Brain: FA are bound to albumin in plasma –> too large to pass through blood-brain barrier
• RBCs: No mitochondria for beta oxidation to occur