Fatty Acid Oxidation

Question 1

Who discovered the pathway of fatty acid oxidation?

Answer 1

Franz Knoop -1904

Question 2

Where does activation of fatty acid happens?

Answer 2

In the carboxyl end

ATP is essential for activation

Question 3

Sources of fatty acid in the cytosol

Answer 3

1) de novo synthesis
2) hydrolysis of TAGs stored in cell
3) transport of fatty acid from fat depots in the body

Question 4

Where does beta-oxidation happen?

Answer 4

In the mitochondrial matrix

Question 5

Where does activation of fatty acids happen?

Answer 5

In the outer mitochondrial membrane

Question 6

What are the enzymes that activate fatty acids?

Answer 6

Acyl-CoA synthetases

Question 7

Characteristics of Acyl-CoA synthetases

Answer 7

1) they are different depending on the length of the fatty acid chain
2) Long: 10-20C, membrane bound, found in ER and mitochondrial membrane
3) Medium: 4-12C, Small: propionate and acetate, found in mitochondrial matrix

Question 8

Activation of Fatty acid process (in principle an endergonic reaction)

Answer 8

Two step reaction:

1) nucleophilic attack to atp -> release ppi
2) activated carboxyl group is attacked by nucleophilic thiol group (sulfur)
3) Two ATPs are required because it goes from ATP to AMP

Question 9

Name of activated fatty acid?

Answer 9

Fatty acyl CoA

Question 10

Movement of long fatty acyl CoA through outer membrane

Answer 10

CPT I (carnitine acyltransferase I)
Location: anchored in the outer mitochondrial membrane with bs facing the cytoplasm
Function: yields fatty acyl-carnitine (carrier)

Question 11

Fatty acyl-carnitine in IMS

Answer 11

1) enters ims through pores

2) moves through it with the help of carnitine-acylcarnitine translocase

Question 12

Fatty acyl-carnitine through inner membrane

Answer 12

CPT II
Location: associated with matrix side of inner membrane
Function: exchanges fatty acyl-carnitine and CoA, releases free carnitine, and produces long-chain fatty acyl-CoA.

Question 13

Translocase that aids CPTII

Answer 13

antiporter: reversible exchange of acylcarnitine for free carnitine

Question 14

Regulation of fatty acid oxidation?

Answer 14

Rate limiting step: fatty acid oxidation entering the mitochondrial matrix

Question 15

what are the stages of fatty acid oxidation?

Answer 15

1) Activation of fatty acids (in outer mitochondrial matrix)
2) Transport into the mitochondria
3) Degradation to two-carbon fragments (in the mitochondrial matrix) (beta-oxidation pathway)

Question 16

Beta-Oxidation of unsaturated fatty acids

Answer 16

1) Most unsaturated fatty acids exists in the cis form
2) Enoyl-CoA hydratase can only act on trans compounds
3) They require an extra enzyme to convert the cis bond to trans

Question 17

Enzyme fo monounsaturated fatty acids

Answer 17

enoyl-CoA isomerase

Question 18

Enzyme for polyunsaturated fatty acids

Answer 18

2,4-dienoyl-CoA reductase (NADPH dependant)

Question 19

where does Beta-Oxidation of odd-chain fatty acids occur? What is the final product?

Answer 19

1) In bacteria and microorganisms

2) propionyl-CoA

Question 20

What are the 3 enzymes for oxidation of odd f.a?

Answer 20

1) Propionyl-CoA carboxylase (biotin coenzyme)
2) Methylmalonyl-CoA epimerase
3) Methylmalonyl-CoA mutase (B12 coenzyme)

Question 21

Possible disorders if propionyl-CoA is not properly catabolized?

Answer 21

methylmalonic acidemia: when (R)-methylmalonyl-CoA can not be properly converted to succinyl CoA, it accumulates and exists the clel in the form of methylmalonic acid, which lowers the blood pH and causes damage to the central nervous system.

Question 22

Regulation of fatty acid oxidation

Answer 22

1) Availability of substrates (fatty acids, which is controlled hormonally by fat movilization from adipocytes).
2) Malonyl-CoA inhibits fatty acyl-CoA transport to mitochondria by carnitine shuttle