Fatty acid synthesis

Question 1

What are the functions of fatty acids?

Answer 1

• Energy storage-Triacylglycerol
• Signlling- Prostaglandins (arachidonic acid)
• Membrane structure- Phospholipid
• Attachment to proteins-
  
  • Myristoylation (glycine)
  • Palmitoylation (cysteine)

Question 2

Show Fatty Acid Synthesis in Adipose Tissue

Answer 2

Question 3

State the Site of Fatty Acid Synthesis

Answer 3

• Fatty acids are synthesized in the cytosol.
• However acetyl CoA is generated from pyruvate in the mitochondrion.
• The inner membrane of the mitochondrion is impermeable to acetyl CoA.

Question 4

How does the acetyl CoA get out of the mitochondrion?

Answer 4

Acetyl CoA Exits the Mitochondrion as Citrate

Question 5

Describe Fatty Acid Synthesis

Answer 5

• Repetitive addition of two-carbon units to a growing hydrocarbon chain.
• Growing chain attached to acyl carrier protein (ACP).
• Occurs in the cytosol.
• Adult mammals – liver cells and adipocytes.

Question 6

What are the sequence of events in fatty acid synthesis?

Answer 6

• 1. Production of acetyl ACP and malonyl ACP.
• 2. Initiation – condensation of acetyl and malonyl groups to produce C4 precursor and CO2.
• 3. Elongation – acyl group on ACP extended by C2 units from malonyl ACP.

Question 7

Synthesis of Acetyl and Malonyl ACP

Answer 7

Question 8

Fatty Acid Synthesis - Initiation

Answer 8

• Acetyl CoA carboxylase is a key site of regulation.
• Has biotin as a cofactor to carry “activated CO2”.

Question 9

Activity of KAS

Answer 9

Question 10

Fatty Acid Synthesis - Elongation

Answer 10

Question 11

β-ketoacyl ACP Reductase

Answer 11

Question 12

3-hydroxyacyl ACP dehydratase

Answer 12

Question 13

Enoyl ACP Reducatase

Answer 13

Question 14

Give a Summary of Elongation

Answer 14

Question 15

Show the structure of Mammalian Fatty Acid Synthase

Answer 15

Dimer of two 270 kDa proteins

Question 16

Condensation Reaction of Fatty Acid Synthesis

Answer 16

• Growing fatty acid chain at KS
• Combines with malonyl CoA on ACP
• ACP carries product between active sites for:

–Reduction (KR)

–Dehydration (DH)

–Reduction (ER)

Question 17

Fatty Acid Release

Answer 17

•Produces 16- and 18-carbon fatty acids.

–Limited by size of enzyme active site.

–Extended further by elongases.

•Fatty acid released from ACP by thioesterase.

Question 18

Overall Reaction

Answer 18

Question 19

Global Regulation of fatty acid synthesis

Answer 19

Occurs at acetyl CoA carboxylase

Question 20

Globa regulation: hormonal control

Answer 20

Question 21

Global Regulation occurs at acetyl CoA carboxylase.

Answer 21

Question 22

Insulin is released in response to high glucose.

What does this activate?

Answer 22

–Activates protein phosphatase 2A to dephosphorylate acetyl CoA carboxylase.

–Fatty acid synthesis is switched ON.

Question 23

Adrenaline and glucagon released when the body is short of energy.

What does this inhibit?

Answer 23

–Inhibits protein phosphatase 2A by phosphorylation.

–Fatty acid synthesis is switched OFF.

Question 24

Insulin Stimulates FA Synthesis at Several Sites

Answer 24

Question 25

Describe local regulation of fatty acid synthesis

Answer 25

* AMPK is activated by AMP and inhibited by ATP. * Acts as a fuel gauge. * When there is plenty of energy FA synthesis is turned on. * Acetyl CoA carboxylase is allosterically regulated by citrate. * [Citrate] is high when high [ATP] and high [acetyl CoA]. * Facilitates polymerisation of inactive dimers of enzyme to active oligomers. * Also inhibited by high [palmitoyl CoA] i.e. excess FA.

Question 27

Citrate can also partially overcome the inactivating effect of phosphorylation.

Answer 27