4. Energy storage (lipids)

Question 1

How is energy in excess of requirements stored long term?

Answer 1

As triaglycerols - esterification of 1 glycerol + 3 fatty acids

Question 2

Why are TAGs an efficient method for energy storage?

Answer 2

i) can be stored in bulk in anhydrous form (hydrophobic) in adipose tissue
ii) highly calorific - energy content per gram twice that of carbohydrate or protein

Question 3

Which situations promote TAG mobilisation?

Answer 3

prolonged aerobic exercise, stress situations (eg starvation), pregnancy

Question 4

Which hormones promote or inhibit lipid storage?

Answer 4

Promoted by:
- insulin

Reduced by:

• glucagon
• adrenaline
• cortisol
• growth hormone
• thyroxine

Question 5

How many adipocytes does an average adult have and how much does this weigh?

Answer 5

~30 billion adipocytes, weighing ~15 kg

Question 6

How do adipocytes change to accomodate increased fat storage during weight gain?

Answer 6

1) can increase in size about 4 fold before…

2) dividing and increasing total cell number

Question 7

How is dietary TAG absorbed from the small intestine into intestinal epithelial cells?

Answer 7

1. TAG broken down into fatty acids + glycerol by pancreatic lipase.
2. absorbed into epithelial cell.
3. reconverted to TAG

Question 8

How does TAG travel from intestinal epithelial cells into the blood?

Answer 8

1. packaged into chylomicrons
2. enters lymphatic system and travels to thoracic duct in left subclavian vein
3. enters blood

Question 9

What are the 2 fates of TAGs in blood?

Answer 9

1. utilisation in tissues for energy production via fatty acid oxidation (not in RBCs lacking MT or in brain as FAs cannot pass blood-brain barrier)
2. storage in adipase tissue

Question 10

Where does lipogenesis occur?

Answer 10

Mainly in cytoplasm of hepatocytes

Question 11

How is dietary glucose converted for use in lipogenesis?

Answer 11

Dietary glucose is major source of carbon… converted to pyruvate in cytoplasm (glycolysis)… pyruvate enters mitochondria and forms acetyl-CoA and oxaloacetate (in TCA) which then condense to form citrate… citrate is moved into the cytoplasm and cleaved back to acetyl-CoA and OAA.

Question 12

Describe the 2 main enzyme reactions required for fatty acid synthesis (lipogenesis) from acetyl~CoA.

Answer 12

1. acetyl-CoA carboxylase produces malonyl-CoA (3C) from acetyl-CoA (2C) - requires biotin.
2. fatty acid synthase complex builds fatty acids by sequential addition of 2C units provided by malonyl-CoA (CO2 release).

Question 13

What are the energy requirements for lipogenesis and how are these met?

Answer 13

• Requires ATP (for acetyl-CoA carboxylase activity) and NADPH (for fatty acid synthase complex activity).
• NADPH provided via the pentose phosphate pathway and conversion of malate to pyruvate by malic enzyme.

Question 14

What is the key regulatory enzyme in lipogenesis and how is this regulation achieved?

Answer 14

Acetyl-CoA carboxylase - controls rate of fatty acid synthesis

1. allosteric regulation
   - citrate activates
   - AMP inhibits
2. hormonal phosphorylation/dephosphorylation
   - insulin activates (promotes dephosphorylation)
   - glucagon and adrenaline inhibit (promote phosphorylation)

Question 15

What happens to the fatty acids produced by lipogensis in the liver?

Answer 15

i) Esterified to glycerol-3-P from glycolysis to form TAG.

ii) Transported out of hepatocyte as VLDL.

Question 16

Compare fatty acid synthesis and beta-oxidation.

Answer 16

Fatty acid synthesis
1- cycle of reactions that add C2 as malonyl CoA
2- consumes acetyl-CoA
3- occurs in cytoplasm
4- multi-enzyme complex (cytoplasm)
5- reductive - requires NADPH
6- requires large amount of ATP to drive process
7- intermediates are linked to fatty acid synthase by carrier protein
8- regulated directly by activity of acetyl-CoA carboxylase
- glucagon/adrenaline inhibit
- insulin stimulates

Fatty acid oxidation
1- cycle of reactions that remove C2 as acetyl-CoA
2- produces acetyl-CoA
3- occurs in mitochondria
4- separate enzymes (MT matrix)
5- oxidative - produces NADH and FADH2
6- requires small amount of ATP to activate the fatty acid
7- intermediates are linked to CoA
8- regulated indirectly by availability of fatty acids in MT
- glucagon/adrenaline stimulate
- insulin inhibits

Question 17

How is fat mobilisation (lipolysis) from adipocytes achieved?

Answer 17

1. triaglycerol cleaved into glycerol + free fatty acids by hormone sensitive lipase
2. products move to blood:
   - glycerol travels to liver and utilised as C source for gluconeogensis
   - free fatty acids travel to muscle and other tissues for B-oxidation complexed with albumin

Question 18

How is the activity of hormone-sensitive lipase controlled?

Answer 18

1. activated (phosphorylated) by glucagon and adrenaline

2. inhibited (dephosphorylated) by insulin