Fatty acid breakdown (18)

Where does FA breakdown happen?

Mitochondria

What happens just after a meal?

1. Adipocytes store FAs in lipid droplets

2. Liver uptakes FAs from chylomicrons

What conditions are necessary for FA breakdown? (2)

1. Prolonged exercise (diagram of woman running)

2. Exhausted glycogen stores

Where do FAs come from? (4)

1. Lipolysis (lipid droplets)

2. Diet (chylomicrons)

3. Liver (VLDL)

4. Phospholipases (Land’s cycle)

Why is transport a problem for FAs?

Bc they are 16C long chain

Step #1 of FA transport

Activation by CoA (E from 2 ATP) = keeps FA inside the cell + gradient

Step #1.5 of FA transport

Reaction is driven forward/catalyzed by PPi + H₂O → 2Pi

Step #2 of FA transport

Combine w/ carnitate via CPT1 (RATE LIMITING STEP)

Step #3 of FA transport

Transport inside the matrix via carnitine:acylcarnitine translocase

Step #4 of FA transport

FA release by CPT2 + recycled carnitate

What’s the regulator of CPT1?

Inhibited by malonyl-CoA (released during FA synthesis)

What is Acyl-CoA’s role during the dehydrogenation step?

Oxidation of 16C acyl-CoA : Palmitoyl-CoA

What energy intermediates are produced during β-oxidation of saturated FAs?

1 NADH and 1 FADH₂ at each cycle = 7 NADH + 7 FADH₂

Crude equation for β-oxidation

Fatty acyl-CoA → Acetyl-CoA

How do the electrons from FADH₂ get into the ETC?

FAD (co-factor) bound to an ETF

What important step is different in the β-oxidation of unsaturated FAs?

Dehydrogenation replaced by isomerisation

What does that difference mean energetically?

No FADH2 produced

What if the FA is evenly polyunsaturated (unsat. on an even carbon)?

FADH2 produced normally + costs 1 NADPH

What if the FA is oddly poyunsaturated (unsat. on odd carbon)?

No FADH2

What happens when the FAs have an odd number of carbons?

Normal β-oxidation until last 3 carbons = propionyl-CoA

What happens to propionyl-CoA?

Converted to succinyl-CoA → joins CAC (anapleurotic reaction)

What happens to branched FAs (from milk)?

They are broken down in a succession of propionyl-CoA (3C with branch point) and Acetyl-CoA (2C)

In which conditions are ketone bodies generated? (4)

1. Low blood glucose

2. No glycogen in liver

3. Gluconeogenesis has begun (use of oxaloacteate)

4. CAC is shut off (bc no oxaloacetate)

What shunting happens in those conditions?

Acetyl-CoA does not enter CAC unnecessarily

Why is ketogenesis necessary then?

Bc Acetyl-CoA cannot transfer between tissues

What are the main ketone bodies? (3)

1. Acetoacetate

2. Acetone

3. Hydroxybutyrate

How do the brain and heart use those ketone bodies?

Reversal of the thiolase reaction = 2 acetyl-CoA

Which ketone body is usually easily detectable?

Acetone is volatile and can be smelled in breath