FA Metabolism Regulation

Question 1

What reaction ultimately governs whether FAS or B-ox occurs?

Answer 1

Cytosolic ACC reaction

Active ACC = FAS

Inactive ACC = b-ox

Question 2

Affect of phosphorylation on ACC

Answer 2

Active = unphosphorylated

Inactive = phosphorylated

Question 3

Well fed state

—> affect on ACC activity?

Answer 3

1. High insulin —>
2. Activates a phosphatase that keeps ACC in its active form
3. Glucose entering the cell (since [glucose blood] is high) —> converts to pyruvate (glycolysis)
4. Pyruvate —> mitochondrial matrix
5. Converted to acetyl-CoA by PDH complex
6. Acetyl-CoA goes to cytosol
7. ACC reaction converts it to malonyl-CoA
8. FAS

**Malonyl-CoA inhibits CAT1 (beta-ox)

All malonyl-CoA used for FAS and no FA in cytosol can enter mito for beta-ox

**ACC reaction lowers [cytosolic acetyl-CoA] which drives mitochondrial A-CoA to flow down gradient into cytosol from matrix

Question 4

Molecule that allosterically activates ACC in the well fed state

Answer 4

Citrate

Question 5

Fasting state

Affect on ACC activity and how

Answer 5

1. High glucagon
2. PKA pathway activated
3. ACC is phosphorylated = inactive
4. [malonyl-CoA cytosol] are low
5. No inhibition of CAT1
   * at the same time…glucagon stimulates the mobilization of FAs from adipose tissue

As cytosolic [LCFAs] increases —> ACC is allosterically inhibited

Question 6

Ketone bodies

Answer 6

FFAs can also be broken down in the liver to acetyl-CoA and ultimately to ketone bodies

These enter the blood and can be used by other tissues (mostly muscle) for energy…so brain can have the little glucose that is still available

Muscles use KBs more cuz they cannot do gluconeogenesis

Question 7

Ketone bodies that the liver makes

Answer 7

Acetoacetate (1\3 of total)

Beta-hydroxybutyrate (2/3)

Question 8

Spontaneous decarboxylation of acetoacetate in circulation

Answer 8

Forms acetone

Higher ketone circulating —> the more acetone made

Common in uncontrolled Type I diabetes

‘Acetone breathe’