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Intermediary Metabolism > Fatty acid catabolism - Lecture 2 > Flashcards

Fatty acid catabolism - Lecture 2 Flashcards

1
Q

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

A

mt
free
blood

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2
Q

In the first step of FA oxidation what occurs?

A

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.

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3
Q

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

A

Fatty acid activation

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4
Q

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

A

Get activated

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5
Q

Is FA activation favourable?

A

Yes

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6
Q

What is a co-factor of FA activation?

A

CoA (SH is active part)

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7
Q

Where is FA-CoA produced?

A

cytosol

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8
Q

What is difficult with CoA and the mitochondria/cytosol>

A

CoA pools need to be kept separate.

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9
Q

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

A

Via the Fatty acyl-carnithine transporter.

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10
Q

How does FA-CoA get transported into the mt?

Pathway

A

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

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11
Q

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

A

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

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12
Q

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

A

ETC
Coq10
FADH2

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13
Q

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

A

8 acetyl-CoA

Cut 7 times

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14
Q

Palmitic acid makes how many acetyl-CoA?

How much ATP can be generated from this?

A 
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)
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15
Q

What is the first reaction of b-oxidation?

A

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

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16
Q

What is the second reaction of b-oxidation?

A

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

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17
Q

What is the third reaction of b-oxidation?

A

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

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18
Q

What is the fourth reaction of b-oxidation?

A

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.

19
Q

What is the first enzyme of B-oxidation?

A

fatty acyl-CoA DH

20
Q

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

A

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.

21
Q

After each cycle of B-oxidation what is made?

A

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

22
Q

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?

A

2 made
1 used
1 net produced

23
Q

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

A

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

24
Q

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

A

16 since there are 16C

25
Q

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

A

B-oxidation - 7
CAC - 8
Total - 15

26
Q

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

A

B-oxidation - 7
CAC - 24
Total - 31

27
Q

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

A

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

28
Q

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

A

14 made from B-oxidation, 7 used - 7 net from b-oxidation

16 made from CAC

16 + 7 = 23

29
Q

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

A

108 ATP

23 water

30
Q

How is hibernation tied into b-oxidation?

A

During hibernation, energy is used to keep metabolism going.

FA oxidation produces water and energy.

31
Q

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

A

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.

32
Q

What happens when more than one bound is unsaturated?

A

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.

33
Q

What is left for odd-chain fatty acids?

A

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

34
Q

What happens to propionyl-CoA?

A

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

35
Q

What happens to methyl-malonyl-CoA?

A

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

36
Q

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

A 
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.
37
Q

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

A

MMA

methyl-malonyl acidemia

38
Q

When is peroxosimal oxidation of fatty acids pertinent?

A

For long-chain fatty acids

39
Q

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

A

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.

40
Q

What is omega oxidation?

A

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

41
Q

How can the omega end be oxidized?

A

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.

42
Q

At the end of omega oxidation, what is produced?

A

Generate 2 NADH, 1 NADPH used.

Left with succinate, goes to CAC.

43
Q

Where are the enzymes for omega oxidation located in vertebrates?

Intermediary Metabolism (13 decks)

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