Lipid Metabolism: Lipid Biosynthesis

Question 1

What is the role of Acetyl-CoA (ACC) in FA biosynthesis?

Answer 1

Key enzyme as it catalyzes synthesis of Malonyl-CoA (3C compound)

This reaction is the rate limiting step and is irreversible

Question 2

What are the three functional regions of ACC?

Answer 2

Biotin carboxylase domain

Biotin carrier domain

Carboxyltransferase domain

Question 3

How is malonyl-CoA formed?

Answer 3

Biotin carrier domain attaches biotin

Biotin carboxylase domain activates CO2 by attaching it to the biotin ring in an ATP-dependent manner

Then translocate to the other arm where the carboxyltransferase domain transfers the activated CoA from biotin to acetyl-CoA

This forms malonyl-CoA

Question 4

What reaction is similar to the two-step reaction of Acetyl-CoA carboxylase reaction?

Answer 4

Pyruvate Carboxylase

Question 5

What is the role of ACP?

Answer 5

Acyl carrier protein

Question 6

What is the role of DH?

Answer 6

B-hydroxyacyl-ACP dehydratase

Question 7

What is the role of ER?

Answer 7

Enoyl-ACP reductase

Question 8

What is the role of KR?

Answer 8

B-ketoacyl-ACP reductase

Question 9

What is the role of KS?

Answer 9

B-ketoacyl-ACP synthase

Question 10

What is the role of MAT?

Answer 10

Malonyl/acetyl-CoA ACP transacylase

Question 11

What is the role of TE?

Answer 11

Palmitoyl thioesterase

Question 12

What is the energy cost for FA synthesis?

Answer 12

Chemical energy

• group transfer potential of ATP (ACC rxn)
• reducing power of NADPH (two NADPH of FAS rxn)

ATP is used in the synthesis of Malonyl-CoA

NADPH is required to reduce the B-keto group and the double bond

Additional costs (ATP, NADPH) involved because acetyl-CoA is generated in the mitochondria and transported to the cytosol

Question 13

How is acetyl-CoA transported out of mitochondria?

Answer 13

Citrate shuttle

Acetyl-CoA is generated in the mitochondria there is no Acetyl-CoA transporter so use citrate shuttle

Acetyl-CoA is converted to citrate via citrate cycle which can leave the mitochondria

Citrate then gets converted to oxaloacetate (with the use of citrate lyase that uses an ATP) which in the process produces an Acetyl-CoA in the cytosol.