Lecture 14: Fatty Acid Catabolism

Question 1

Characteristics of Fats versus Polysaccharides:

Answer 1

• Long-term energy needs: slower delivery vs. glucose/glycogen
  - Nonpolar: Fatty acids carry less water along
  - More reduced: Fatty acids carry more energy per carbon.
  - FA: 9 kcal/gram
  - Carbohydrates, proteins: 4 kcal/gram

Question 2

Three main processes of how we get energy from fats:

Answer 2

1. Break down TAG into fatty acids and glycerol (lipolysis)
   - transport in blood tissues that need energy.

        2. Activate fatty acids for transport into mitochondria.
        3. Oxidize fatty acids to acetyl-CoA for TCA cycle/

Question 3

Lipolysis: mobilization of TAG’s

Answer 3

○ HSL: hormone sensitive lipase
○ ATGL: adipose triacylglycerol lipase
○ MGL: monoacylglycerol lipase

Question 4

How do free fatty acids travel?

Answer 4

§ leave adipose tissue.
§ travel through blood bound serum albumin.
§ arrive at tissues that need them for energy (or get re-stored).

Question 5

Fates of Dissociated TAG’s: Glycerol:

Answer 5

§ enters glycolysis as GAP.

			- glycerol---> G3P  DHAP  GAP
			- Requires ATP and glycerol kinase.
			- could do gluconeogenesis instead.
			- Limited anaerobic catabolism of fats.

Question 6

Fats of Dissociated TAGs: Fatty Acids

Answer 6

§ Oxidized for fuel (TCA cycle) or re-stored
§ If fuel, must be converted to fatty acyl-CoA (activation).
○ Now that FA is in tissue, must get it into the mitochondria
§ activate it (add CoA)
§ enzyme is acyl-CoA synthetase

Question 7

Fatty Acid Activation:

Answer 7

○ Two step reaction catalyzed by acyl CoA synthetase.

		1. Add ATP, remove PP
		2. Add CoASH, remove AMP
			- thioester formed (product is acyl CoA).

Question 8

Transport of Fatty Acyl-CoA:

Answer 8

○ Fatty acid activation: cytoplasm
○ Fatty acid degradation (Beta oxidation): mitochondrial matrix
○ Transporting fatty acyl-CoA into the mitochondria is the rate limiting step.
§ Acyl CoA can cross the outer but not the inner mitochondrial membrane.
○ Small fatty acids (<12 carbons) diffuse freely across mitochondrial membranes.
○ Larger fatty acids (most free FA’s) transported via acyl carnitine/carnitine transporter.

Question 9

Acyl-Carnitine/Carnitine Transport:

Answer 9

1. Carnitine acyltransferase-I (CAT-I): transfers acyl to carnitine
   - Malonyl-CoA inhibits this enzyme (rate limiting step)
   2. Carnitine translocase: carries acylcarnitine into the matrix
   3. CAT-II: transfer acyl from carnitine to CoASH to regenerate acyl-CoA

Question 10

Beta Oxidation Three Main Stages:

Answer 10

○ Fatty acids (in mitochondria) can now be oxidized as fuel.
○ Three main stages:
1. Beta oxidation:
- Oxidation of chain and cleavage as AcCoA
- Make 1 NADH, 1 FADH2 per round of beta oxidation.
- Leave (e-) and cleave 92-C)
2. TCA cycle:
- Oxidation of AcCoA—> 2 CO2
- More NADH and FADH2 made!
3. ETC
- NADH and FADH2 —> ATP