Beta Oxidation Of Fatty Acids

Question 1

The breakdown of Fatty acids occurs in the mitochondria but fatty acids reside in the cytosol. How do we get them into the mitochondria?

Answer 1

Carnitine cycle.
- large chain fatty acids are converted to fatty acyl-CoA by fatty acyl CoA synthase.
- CAT-1 then performs the rxn:
Fatty acyl CoA + carnitine –> fatty acyl carnitine + CoA
- Fatty acyl carnitine can then traverse the inner mitochondrial membrane.
- CAT II then performs the rxn:
Fatty acyl carnitine + CoA –> fatty acyl CoA + carnitine

— so in summary, we have exactly what wwe started with but Now in the mitochondria.

Question 2

Loosely speaking, what is the mechanism for beta oxidation?

Answer 2

We shorten the carbon chain by 2 carbons each time using a series of reactions on the 3rd Carbon.
- releases 1 NADH, FADH, and Acetyl CoA

Question 3

What is the energy yield difference In an unsaturated fatty Acid?

Answer 3

Less FADH2 because they are already partially oxidized and correspondingly less ATP.

Question 4

WHats the deal with medium chain fatty acids?

Answer 4

• They don’t need the carnitine shuttle to enter the mitochondria
• MCAD is required for oxidation.

Question 5

If you have an odd number of carbons how do we break it down?

Answer 5

We start with propionyl-CoA, which is carboxylated by proportional-CoA carboxylase (ABC carboxylase) to methylmalonyl-CoA.
- Requires biotin.

Methylmalonyl-CoA then gets converted into Succinnyl-CoA so that it can enter the TCA cycle.
- This is done through the enzyme methylmalonyl-CoA mutate, which requires Vitamin B12.

Question 6

CPT-1 deficiency

Answer 6

Affects the liver and presents with hepatomegaly.

• hypoketotic hypoglycemia
• elevated carnitine

Question 7

CPTII deficiency

Answer 7

Adults - affects mostly skeletal muscle. Causes muscle pain, fatigue, and myoglobinuria.
Infantile - presents in 6-24 months of life. Hypoketotic and hypoglycemic. Hepatomegaly and cardiomyopathy
Neonatal - presents within 4 days. Respiratory failure, hapetomegaly, seizures, hypoglycemia, cardiomegaly, cardiac arrhythmias.

Question 8

Impaired oxidation of medium chain fatty acids

Answer 8

• autosomal recessive
• hypoketotic hypoglycemia
• high concentrations of medium chain carboxylic acids in plasma and urine
• hyperammonemia

— treatment - don’t fast and frequent feeding. Carnitine supplementation.

Question 9

Deficiency in methylmalonyl CoA mutase

Answer 9

Can occur due to Vitamin B12 deficiency, IF, or the actual enzyme.

• Will have methylmalonyl aciduria.
• may cause peripheral neuropathy

Question 10

What is beta oxidation?

Answer 10

It is the breakdown of fatty acids.

• the reason that it is called beta oxidation is because it occurs at the beta carbon.
• generation of FADH2 and NADH
• occurs in the mitochondria