Oxidation of Fatty Acids

Question 1

Discuss how we get fatty acids inside to do fatty acid oxidation

Answer 1

In the cytosol of the cell, long chain fatty acids are activated by ATP and coenzyme A to make fatty acyl-CoA. Short chains do this too, but can do it inside the mitochondria. We use 2 ATP to do this first step.

But fatty acyl CoA still can’t cross the membrane. Now that it is activated though, it can react with carnitine to make fatty acyl carnitine, which goes through the membrane via carnitine acyltransferase I.

Inside the inner membrane, it reforms fatty acyl CoA and carnitine goes back outside via CAT II.

Question 2

What inhibits the carnitine shuttle?

Answer 2

Malonyl-CoA, an intermediate in fatty acid synthesis. That way we aren’t just making fatty acid to immediately destroy it.

Question 3

So now we have this fatty acyl CoA inside of the mitochondria. What now?

Answer 3

We begin beta oxidation.

Right by the carbon double donded to oxygen is the alpha carbon, and it is the one we are targeting first. Recall that the point of these steps is to make energy, and we only have a few. So right from the start, we are doing to oxidize the fatty acyl CoA with an acyl CoA dehydrogenase to turn FAD to FADH2.

This gives us trans fatty anoyl CoA

Question 4

So right off the bat we went ahead and broke a double bond at the alpha carbon. Why? What next?

Answer 4

We need to put a double bond between the alpha and beta carbon to make it more ready to except an O at the beta carbon (Beta oxidation is the key here).

Now that there is a double bond, we can add water across it with enoyl CoA Hydratase to turn our trans fatty enoyl CoA to a Beta Hydroxy acyl CoA, which guess what, has an OH on its beta carbon now.

Question 5

So now we have put OH on the Beta carbon, what next?

Answer 5

Remember, the point is to make energy. Oxidizing the Beta hydroxy acyl CoA with Beta hydroxy acyl CoA dehydrogenase (we are getting really original with these names now, keep up), we turn NAD+ to NADH and our Beta hydroxy to a Beta keto acyl CoA.

Question 6

What do we do with this Beta keto acyl CoA?

Answer 6

This thing is garbage, we’ll break it up to make it more useful.

Take Beta keto thiolase and turn it into a shorter (minus two) fatty acyl CoA and an acetyl CoA.

Question 7

So with a big even carbon like Palmitate, how many ATP will we make?

Answer 7

Palmitate means 16 carbons, so:

1. 16 to 14
2. to 12
3. to 10
4. to 8
5. to 6
6. to 4
7. to 2 (both acetyl CoAs)

So we did 7 rounds, so 7 FADH2 and 7 NADH, and 8 Acetyl CoA - 2 ATP that we needed to turn the palmitate in the very first go around to fatty acyl CoA
71.5 + 72.5 + 8*10 ATP (per TCA cycle) makes 108 - 2 to start up = 106

Question 8

What do we do about odd chained fatty acids?

Answer 8

They go through the same thing, but in the end they make an acetyl CoA (2C) and a propionyl CoA (3C) which we can turn into glucose!

Question 9

What do we do with Very Long Chain Fatty Acids

Answer 9

The process differs for these guys

• No FADH2
• O2 is used
• H2O2 is formed

Then since they are shorter they go to the mitochondria from the peroxisomes to do normal beta oxidation.

Question 10

Zellweger syndrome

Answer 10

Defect in peroxisomal biogenesis that leads to accumulation of VLCFA in tissues, affecting the liver and the brain. We see elevated C26 and 26:1 in plasma.

The patients tend to have neural and optic abnormalities

Question 11

Refsum disease

Answer 11

Alpha hydroxylase deficiency causing a high level of phytanic acid from plants to build up in tissues, leading to neural issues.

Treat with reducing leafy intake.

Question 12

What are the four main fatty acid components of our diet and what are there structures?

Answer 12

Palmitate - C16:0
Stearate - C18:0
Oleate - C18:1 Delta 9
Linoleate - C18:2 Delta 9, 12

Question 13

What carries FAs in the blood?

Answer 13

Albumin carries it, drops it off, it travels to the mitochondrial matrix.

Question 14

What are the fatty acid chain length names?

Answer 14

VLCFA = 20+
LCFA = 12 - 20
MCFA = 6 - 12
SCFA =

Question 15

What is the problem with doing Beta Oxidation of Unsaturated FAs?

Answer 15

May create an intermediate with a C=C in the C3-C4 position rather than the 2-3.

Cis double bonds are not recognized by enoyl CoA hydratase

Question 16

What enzymes do we use to work through the problems we face with unsaturated fatty acid beta oxidation?

Answer 16

Enoyl CoA Isomerase - Puts the 3-4 C=C at 2-3 C=C

2,4 dienoyl reductase, which uses NADPH - Takes a C=C at 2-3 and C=C 4-5 and turns it into one C=C 3-4

Question 17

How do we turn propionyl CoA to other things?

Answer 17

Propionyl CoA is one of our products of odd chain Fatty acids. With Propionyl CoA Carboxylase (need Biotin), we maye a methylmalonyl CoA (one of two forms which we can swap between using MMCoA epimerase).

MMCoA via MMCoA mutase can turn to Succinyl CoA (need B12)