Fatty acid catabolism - Lecture 2

Question 1

All the enzymes involved in oxidation of FA are present in the ________.
The _____ FA obtained from the ______ cannot enter the mt.

Answer 1

mt
free
blood

Question 2

In the first step of FA oxidation what occurs?

Answer 2

FA are conveted to Fatty acyl-CoA on the outer mt membrane by Fatty acyl CoA synthetase (aka thiokinase)
This reaction is coupled with ATP hydrolysis to AMP and two Pi.

Question 3

What is the regulatory step for the fatty acid oxidation pathway?

Answer 3

Fatty acid activation

Question 4

What happens to FAs before they can be transported into the mt?

Answer 4

Get activated

Question 5

Is FA activation favourable?

Answer 5

Yes

Question 6

What is a co-factor of FA activation?

Answer 6

CoA (SH is active part)

Question 7

Where is FA-CoA produced?

Answer 7

cytosol

Question 8

What is difficult with CoA and the mitochondria/cytosol>

Answer 8

CoA pools need to be kept separate.

Question 9

How is FA-CoA (or just the FA in this case), transported into the mt?

Answer 9

Via the Fatty acyl-carnithine transporter.

Question 10

How does FA-CoA get transported into the mt?

Pathway

Answer 10

Carnithine is present in the cytosol.
FA group of Fatty acyl CoA is transferred to the OH group of carnithine by carrnityl acyl transferase 1 (CAT-1).
Fatty acyl–CArnitine estter is trnasported into the mt by a transporter.
CoA present in the cytosol attacks carnitine-FA (catalyzed by CAT-II), removing carnitine and reforming FA-CoA.
Carnitine is transported back out of the mt

Question 11

Utilization of FA for oxidation and generation of ATP is achieved in three steps, these are?

Answer 11

1 - Beta oxidation of FA chain yielding acetyl-CoA

2 - Entry of acetyl-CoA in CAC yielding NADH, FADH2 and GTP

3 - Utilization of NADH and FADH2 in oxidative phosphorylation to generate ATP

Question 12

The first fatty-acyl CoA DH enzyme of B-oxidation is liked to _____ and it directly transfers to ____ in ETC via _____.

Answer 12

ETC
Coq10
FADH2

Question 13

If there is a 16C long FA, palmitic acid, how many acetyl-CoA will be generated?
How many times will it be cut?

Answer 13

8 acetyl-CoA

Cut 7 times

Question 14

Palmitic acid makes how many acetyl-CoA?

How much ATP can be generated from this?

Answer 14

Acetyl-CoA - 3 NADH, 1 FADH2, 1 GTP
3 NADH = 7.5 ATP
1 FADH2 = 1.5 ATP
So, per acetyl-CoA, get 10. 
So, 80 ATP (should be 108)

Question 15

What is the first reaction of b-oxidation?

Answer 15

The first enzyme catalyzes formation of a trans, alpha-beta bond.
uses FAD as a cofactor.
Enzyme linked to ETC via electron transferring flavoprotein

Question 16

What is the second reaction of b-oxidation?

Answer 16

Hydration of the double bond by enoyl-CoA hydratase to form L-B-hydroxylacyl-CoA

Question 17

What is the third reaction of b-oxidation?

Answer 17

NAD+-dependent dehydrogenation by L-B-hyoxylacyl-CoA DH to form B-ketoacyl-CoA

Question 18

What is the fourth reaction of b-oxidation?

Answer 18

Alpha-beta carbon bond cleavage in athiolysis reaction with CoA.
Catalyzed by thiolase, produces acetyl-CoA and a new fatty-acyl-CoA with 2 fewer carbon units.

Question 19

What is the first enzyme of B-oxidation?

Answer 19

fatty acyl-CoA DH

Question 20

Where is fatty-acyl-CoA DH located? What does this mean?

Answer 20

Bound to mt membrane like succinate DH.

FADH2 produced from this reaction is quickly grabbed by complex 2 and the electrons are transferred to coq10.

Question 21

After each cycle of B-oxidation what is made?

Answer 21

NADH, FADH2, acetyl-CoA and a fatty-acyl chain with 2 fewer carbon units.

Question 22

How many water molecules are made from each cycle of B-oxidation.
How many are used?
What is the net synthesis or use of water?

Answer 22

2 made
1 used
1 net produced

Question 23

So, going back to the earlier calculation. How many ATP are generated from 1 palmitic acid?

Answer 23

B-oxidation
8 acetyl-CoA produced
7 NADH - 17.5
7 FADH2 - 10.5

CAC
8 GTPS - 8 ATP
24 NADH - 60
8 FADH2 - 12

Total = 108 ATP

Question 24

From a 16C FA, how many CO2 are made?

Answer 24

16 since there are 16C

Question 25

How many FADH2 are produced from B-oxidation of palmitic acid?

Answer 25

B-oxidation - 7 CAC - 8 Total - 15

Question 26

How many NADH are produced from B-oxidation of palmitic acid?

Answer 26

B-oxidation - 7 CAC - 24 Total - 31

Question 27

How many total water molecules are produced by B-oxidation?

Answer 27

B-oxidation 2*7 = 14 CAC 8 *2 = 16

Question 28

How many net water molecules are made from B-oxidation?

Answer 28

14 made from B-oxidation, 7 used - 7 net from b-oxidation 16 made from CAC 16 + 7 = 23

Question 29

Each mol of palmitic acid completely oxidized produces how many ATP and how much water, net?

Answer 29

108 ATP | 23 water

Question 30

How is hibernation tied into b-oxidation?

Answer 30

During hibernation, energy is used to keep metabolism going. | FA oxidation produces water and energy.

Question 31

What is the difference for oxidation of saturated vs. unsaturated fatty acids?

Answer 31

All the steps are the same except in unsaturated FAs, there is an additional enzyme, enoyl-CoA isomerase, moves double bond to beta carbon. First step of b-oxidation is then take care of.

Question 32

What happens when more than one bound is unsaturated?

Answer 32

Additional enzyme, 2,4 dienoyl reductase prior to isomerization reaction and b-oxidation. Also, need to use NADPH to saturate bond. Reducing reactin used to saturate bond.

Question 33

What is left for odd-chain fatty acids?

Answer 33

A three carbon unit, propionyl-CoA, is left at the last cycle of b-oxidation

Question 34

What happens to propionyl-CoA?

Answer 34

Converted to four carbon methyl-malonyl-CoA by propionyl-CoA carboxylase and methyl-malonyl-CoA epimerase.

Question 35

What happens to methyl-malonyl-CoA?

Answer 35

Converted to succinyl-CoA by methyl-malonyl-CoA mutase, which uses vitamin B12 as a cofactor.

Question 36

What is the purpose of methyl-malonyl-CoA epimerase?

Answer 36

``` The carboxylase (propionyl-CoA carboxylase) generates methyl-malonyl-CoA but, in the D conformation. This enzyme thus converts it to the L form. The carboxylic group is transferred to another carbon and replaced with CoA. ```

Question 37

What disease does a person get if methyl-malonyl-CoA is defective?

Answer 37

MMA | methyl-malonyl acidemia

Question 38

When is peroxosimal oxidation of fatty acids pertinent?

Answer 38

For long-chain fatty acids

Question 39

What is the difference between normal beta-oxidation and peroxisomal oxidation of fatty acids?

Answer 39

Most of the steps are the same but, first enzyme is not linked to ETC in peroxisome. Electrons from the first reaction are directly transferred to O2 to generate hydrogen peroxide. Catalase then quenches hydrogen peroxide. In the third step, NADH produced but, cannot give electron to complexes in peroxisome. Gets transported out into the cytosol. Eventually used up by mt. When the FA gets shorter, brought to mt.

Question 40

What is omega oxidation?

Answer 40

IF the FA is long enough, can be oxidized at both ends, beta and omega carbons.

Question 41

How can the omega end be oxidized?

Answer 41

Methyl group converted to almost aldehyde (Adds hydroxyl to methyl part) using oxygen as an oxidizing agent and NADPH as a reducing agent. Then, further oxidized, alcohol oxidized to aldehyde and then aldehyde oxidized to acid.

Question 42

At the end of omega oxidation, what is produced?

Answer 42

Generate 2 NADH, 1 NADPH used. | Left with succinate, goes to CAC.

Question 43

Where are the enzymes for omega oxidation located in vertebrates?

Answer 43

ER