Lipid Metabolism: FA Catabolism

Question 1

What is the fate of glycerol released by TAG hydrolysis?

Answer 1

Oxidation via glycolysis

Glyercerol-3-P can be used in TAG or glycerophospholipid synthesis

Question 2

What is the fate of FA-CoA?

Answer 2

Transported into mitochondrion for oxidation
- attached to OH group of caratine to form FA-caratine

Used in cytosol to synthesize membrane lipids / TAGs

Question 3

What is the carnitine transport cycle?

Answer 3

A 3-step process that translocates FAs across the inner mitochondrial membrane

Question 4

What are the two important functions of the carnitine shuttle?

Answer 4

TLDR:

1. Control flux of FA
   - degradation, FA into the mitochondrial matrix
   - synthesis of TAGs and membrane lipids in cytosol
2. Maintains separate pools of CoA
   - cystolic CoA = anabolic
   - mitochondrial CoA = catabolic

control the flux of FAs either into the mitochondrial matrix for DEGREDATION or toward SYNTHESIS of TAGs and membrane lipids in the cytosol
- activity of carnitine acyl transferase is negatively regulated by Malonyl CoA (precursor for FA synthesis)

Maintains separate pools of Coenzyme A

• Cystolic CoA = used for anabolic pathways (FA synthesis)
• Mitochondrial CoA = used for catabolic pathways such as degradation of FAs, pyruvate, and some AAs.

Question 5

What is the fate of FA-CoA?

Answer 5

Transported to mitochondria for oxidation (forms FA-carnitine)

Used in the cytosol to synthesize membrane lipids/TAGs

Question 6

What is beta oxidation? Why is it called so?

Answer 6

Step-wise oxidation of the fatty acyl group at the C3 or B-position (hence the name B-oxidation)

Question 7

What happens to the NADH, FADH2, and acetyl-CoA produced during beta oxidation?

Answer 7

Stage 1: B-oxidation

Stage 2: Oxidation of acetyl-CoA into CO2 (citric acid cycle) with concomitant generation of NADH and FADH2

Stage 3: ETC, generates ATP with NADH and FADH2

Question 8

What are the number of ATP produced by complete oxidation?

Answer 8

7 rounds = 7 NADH, 7 FADH2, 8 Acetyl-CoA
----------------------------------
NADH (x2.5)
FADH2 (x1.5)
Acetyl-CoA =
(x3 Acetyl-CoA) NADH
(x1 Acetyl CoA) FADH2
(x1 Acetyl CoA) GTP (x1)

Palmitoyl-CoA = 108 ATP
Palmitate = 108-2ATP = 106ATP

Question 9

How are monounsaturated FA oxidized?

Answer 9

1. # of cycles of B-oxidation to double bond (3 rounds = 3 acetyl-CoA)
2. Instead of oxidation, use isomerase to change cis bond to trans bond
   - this step loses ATP because FADH2 is not produced meaning a small amount of ATP lost
3. Hydration and Oxidation
4. B-oxidation until all are cleaved resulting into acetyl-CoA

Question 10

Why does liver cells only synthesize ketone bodies and not use them as energy?

Answer 10

Liver cells do not have B-ketoacyl-CoA transferase present

Liver cells do express HMG-CoA lyase which enables them to synthesize ketone bodies

Question 11

How do other tissues convert ketone bodies back into acetyl CoA?

Answer 11

Skeletal and cardiac muscles use these ketone bodies as a source of acetyl-CoA for energy conversion in the citrate cycle

Question 12

Why are too much ketone bodies bad for you?

Answer 12

In starvation and untreated diabetes, ketone bodies will accumulate due to excess acetyl-CoA

Excess levels of ketone bodies will be bad because this can lower blood pH and the tissues will not be able to utilize all of them which would result in pathological conditions