Week 10 Objectives

Question 1

Describe the reaction catalyzed by acetyl-CoA carboxylase and understand the mechanisms by which its activity is regulated to control the rate of fatty acid synthesis.

Answer 1

-ACC converts acetyl-CoA -> malonyl-CoA *regulatory enzyme for FAS

• ACC activated by insulin, citrate, dephosphorylation
• inhibited by glucagon, palmitoyl-CoA, phosphorylation

Question 2

Outline the structure of the fatty acid synthase multienzyme complex, indicating the sequence of enzymes in the two peptide chains of the homodimer.

Answer 2

FA synthase: a multiple peptide enzyme where FAS takes place, includes ACP and thioesterase, synthesizes palmitate (C16)

Primed by acetyl-CoA… homodimer

ACP: formed from pantothenic acid, a derivative of vitamin B

Question 3

Explain how long-chain fatty acids are synthesized by the repeated condensation of two carbon units, with formation of the 16-carbon palmitate being favored in most tissues, and identify the cofactors required.

Answer 3

Start: Malonyl-CoA

• side chain produces this, citrate -> acetyl-CoA -> malonyl-CoA with oxaloacetate and ATP
• oxaloacetate -> malate -> pyruvate (malate dehydrogenase and malic enzyme)

1. Condensation
2. Reduction (NADPH)
3. Dehydration
4. Reduction (NADPH)

End: Palmitate (16C) released from thioesterase

Cofactors: biotin, NADPH, pantothenic acid

Question 4

Indicate the sources of reducing equivalents (NADPH) for fatty acid synthesis.

Answer 4

1. malic enzyme converts malate -> pyruvate
2. priming of ACP thru pantothenic acid
3. elongation of the chain

Question 5

Explain how fatty acid synthesis is regulated by nutritional status and identify other control mechanisms that operate in addition to modulation of the activity of acetyl-CoA carboxylase.

Answer 5

• activated by insulin (fed state pathway)

- fatty acids are packaged into VLDLs as TAGs w/ cholesterol and taken to adipose for storage