Fatty Acid Oxidation

"Do you not know that your bodies are temples of the Holy Spirit, who is in you, whom you have received from God? You are not your own; you were bought at a price. Therefore honor God with your bodies." Corinthians 6:19-20

Where are the enzymes involved in fatty acid oxidation located?

In the mitochondrial matrix, so fatty acids must be modified

How are fatty acids modified?

By the carnatine shuttle

What are the three steps of the carnatine shuttle

1. Fatty acid acitivation by attachment to CoA

2. Fatty acids are then attached to -OH group on carnitine and imported to mitochondria

3. Fatty acid is transferred to mitochondrial CoA

What is the first step of carnitine shuttle

Fatty acyl-CoA snthetase

• ligase

• requires ATP

• forms THIOESTER linkage (like acetyl coA) whihc is a high energy bond

Why does PPi hydrolysis make the first step of the carnitine shuttle favorable

- bc it equivalent to TWO atp molecules being used because AMP is the leaving group at the end and AMP requires two phosphates to go to ATP

What does Fatty Acyl Co-A do

It can be used to synthesie membrane lipids, in cytosol, or implanted into the mitochondrial matrix for energy

What is the second step of carnitine shuttle

Fatty acids are attached onto the -OH group of carnitine and imported to the mitochondria
Catalyzed by carnitine acyl transferase I.

What does CAT1 do?

CAT1 attaches -oh group on carnitine so that fatty acid can be imported to mitochondria. This is fatty acid-carnitine,

How does fatty acid-carnitine enter the mito matrix?

through facilitated diffusion by carnitine transporter

What is the third step of carnitine shuttle?

Fatty acid is transferred to mitochonridal CoA
CAT2
- Carnitine is then shuttled back to cytosol

What are the three stages of oxidation fo fatty acids?

1. Beta oxidation

2. Acetyl-CoA enter the CAC

3. Oxidative phosphorylation to produce ATP

What is stage 1 of oxidation of FA

Beta Oxidation, FA undergoes oxidative removal of a successive two carbon units on the form of acetyl-CoA
- at end of each round of beta-oxidation, FA has two fewer C's then it started with

What is stage two of oxidation of fatty acids?

Acetyl-CoA molecules enter the CAC, each turn yields 3 NADH, 1 FADH2, and 1 GTP

What are the steps of beta oxidation?

1. Oxidation of FA to produce double bond between alpha and beta carbon (trans)

• 1 FADH2 is produced

2. H2O is added across double bond to produce an alcohol

3. Beta-alcohol is oxidized to ketone???

• 1 nadh is produced

4. transfer reaction: acetyl-CoA is released and remaining FA chain is transferred to CoA

alkane to alkene to alcohol to ketone

What happens when ketone --> CoA --> Acetyl-CoA + FA-CoA

the fatty acid is 2C's shorter
so for C14, 6 rounds of Beta-oxidation to produce 7 acetyl-CoA molecules

EXAMPLE of beta oxidation

Palmitate: C16 - 7 rounds of

• Beta-oxidtaion yields 8 acetyl-CoA, 7FADH2, 7 NADH

• Acetyl-CoA goes into the citiric acid cycle

• 24 NADH, 8 FADH2, 8 GTP (ATP)

• For acetyl-CoA, the CAC produces 3 NADH, 1 FADH2, 1 GTP Total NADH: 31, FADH2: 15, ATP:8

2.5 ATP for NADH 1.5 ATP for 1FADH2 -2 for FA activation should be 106 ATP from fa-coa synthetase

How much ATP does one glucose make?

32 ATP

• therefore this is more efficient to store than glucose because fat make a lot more

What happens in the electron transport chain?

FADH2 and NADH donate e- and O2 is the final e- acceptor
1/2 O2 + 2H+ + 2e- --> H2O
- reduction half reaction
-camel hump is full of fat, but when oxidaized it produces h2o
metabolic h2o we produce a few hundred milliliters everyday

What happens if a fatty acid is unsaturated?

Beta oxidation occurs as usual, but the last round yields propionyl-CoA which becomes succinyl-CoA which can enter the CAC cycle

What are the three enzymes required to convert the products of unsaturated FA beta oxidation?

1. propionyl-CoA carboxylase

• biotin

• ATP

2. methylmalonyl-CoA racemase

3. methylmalonyl-CoA mutase

• B12

What is the first step of unsat FA beta oxidation

1. propionyl CoA carboxylase catalyzes conversion of propionyl-CoA to (s) methylmalonyl-CoA
requires biotin an dATP

What is the second step of unsat FA beta oxidation

Methylmalonyl-CoA racemase, catalyzes (s) --> (r) conversion

What is the third step of unsat FA beta oxidation

Methylmalonyl-CoA mutase

• isomerizes (r) methylmalonyl-CoA to succinyl-CoA

• Requires coenzyme B12

• contains corrin ring: heme

• C-co bond is one of two known c-metal bonds in biology

• narrow tunnel in enzyme protects metabolite

• succinyl coa is produced, which then enters the CAC