Regulation of Fatty Acid Synthesis

Question 1

Acetyl-CoA Carboxylase (ACC) is regulated allosterically by

Answer 1

1) Positive allosteric control - Citrate (lots of substrate = produce lots of fatty acid)
2) Negative allosteric control - Fatty acyl-CoA (Palmitoyl-CoA) (too much fatty acid = inhibits its production)

Question 2

Acetyl-CoA Carboxylase (ACC) is regulated covalently by (hormones)

Answer 2

Phosphorylation:
1) Low glucose or fight or flight conditions
2) Glucagon/epinephrine secretion stimulates PKA (through cAMP)
3) PKA phosphorylates ACC.
4) Phosphorylation leads to the inhibition of ACC.
5) Decrease in FA synthesis

Question 3

Acetyl-CoA Carboxylase (ACC) is regulated covalently by (AMPK (energy sensor))

Answer 3

Phosphorylation
1) Low concentration of ATP
2) Increase in AMP leads to the activation by phosphorylation of AMPK
3) AMPK phosphorylates ACC.
4) Phosphorylation leads to the inhibition of ACC.
5) Decrease in FA synthesis

Question 4

Acetyl-CoA Carboxylase (ACC) is regulated covalently by (PP2A))

Answer 4

Dephosphorylation
1) High concentration of glucose
2) Secretion of insulin leads to the stimulation of Protein Phosphatase 2A (PP2A).
3) Dephosphorylation and activation of ACC.
4) Increase in FA synthesis

Question 5

How does insuline effect AMPK

Answer 5

1) The insulin pathway activates another protein phosphatase called PP1.
2) PP1 dephosphorylates and inactivates AMPK.

SIDE NOTE (not important for exam): Another role of the insulin pathway is the activation of a family of enzymes called phosphodiasterases. These enzymes break phosphodiester bonds found in cyclic nucleotide such as cAMP, the activator of PKA.

Question 6

Explain the reciprocal regulation of FA synthesis and b-oxidation

Answer 6

Promotion of FA synthesis: Malonyl-CoA inhibits CPT1 activity to prevent β-oxidation of newly synthesized FAs.

Supression of FA synthesis: High FA concentration suppresses FA synthesis by blocking malonyl-CoA formation at the level of ACC.

Question 7

Summary slides: Compare and contrast the process of β-oxidation and FA synthesis

Answer 7

Question 8

Summary Slide: FA synthesis requires the acitvity of

Answer 8

acetyl-CoA carboxylase (ACC) and fatty acid synthase (FAS)

Question 9

Summary Slide: Acetyl-CoA is transported from the mitochondria to the cytosol in the form of

Answer 9

citrate via tricarboxylate transport system

Question 10

ACC, a biotin-dependent enzyme, catalyzes

Answer 10

ATP-dependent carboxylation of acetyl-CoA resulting in malonyl-CoA