Lecture 26: Fatty acids as a fuel 2

Question 1

Fatty acids used as a fuel molecule are obtained from the
breakdown of what storage molecule in our adipose tissue?

Answer 1

Triacylglycerols (TAGS) in our adipose tissue.

Question 2

The attachment of fatty acids to coenzyme A is called what?

Answer 2

Fatty acid activation

• Fatty acids are activated before β-oxidation
• Occurs before the fatty acid enters the mitochondria
• Activated by attachment to CoA to make a fatty acyl-CoA
• Acyl-CoA Synthetase is the enzyme responsible for this activation

Question 3

In terms of ATP hydrolysis, what is the “cost” of activating fatty acids?

Answer 3

• Energy to add CoA from hydrolysis of ATP to AMP (energy
  equivalent of 2 ATP)

Question 4

Where does β-oxidation occur?

Answer 4

Oxidation of fatty acids occurs in the mitochondrial matrix
(two membranes must be crossed)

Question 5

How is fatty-acyl CoA transported into the mitochondria?

Answer 5

Fatty Acyl-CoA Carrier:
Fatty-acyl CoA is initially transported across the outer mitochondrial membrane using a fatty acyl-CoA carrier.

Conversion to Fatty Acyl-carnitine:
Fatty-acyl CoA is converted to Fatty acyl-carnitine by carnitine acyltransferase I (CAT I) on the outer mitochondrial membrane.

Transport Across the Inner Membrane:
Fatty Acyl-carnitine is transported into the mitochondrial matrix via a protein carrier

Conversion Back to Fatty-acyl CoA:
Inside the matrix, Fatty acyl-carnitine is converted back to fatty-acyl CoA by carnitine acyltransferase II (CAT II).

Question 6

Describe the carnitine acyltransferase reaction briefly:

Answer 6

• Exchanges CoA and carnitine on a fatty acid
• Reversible reaction (converted back to Fatty acyl-CoA in the mitochondrial matrix)

Question 7

How is the energy released during the oxidation of fatty acids harnessed?

Answer 7

• Energy released in β-oxidation is transferred to the
  coenzymes NAD and FAD

These can be used in the electron transport chain to generate ATP

Question 8

What is the other product of β-oxidation (not NADH or FADH2) that can be used in the CAC?

Answer 8

The product of β-oxidation, acetyl-CoA, is further oxidized
in the citric acid cycle

Question 9

Does β-oxidation continue after 1 full cycle?

Answer 9

Yes absolutely

β-oxidation cycle is repeated over and over, cutting two carbon pieces of Fatty acyl-CoA each cycle until the molecule is used up.

This produces many NADH, FADH2 and acetyl-CoA

Question 10

What is the role of FAD? What is it derived from?

Answer 10

FAD: Flavin adenine dinucleotide

• Derived from Riboflavin (vitamin B2)
• A coenzyme required by some enzymes that catalyze redox reactions (including fatty acid oxidation, citric acid cycle)
• Flavin coenzymes are tightly bound to the proteins with which they interact (flavoproteins)

Question 11

What are the two forms of FAD?

Answer 11

FAD
(oxidized form)

FADH2 (reduced form)
Carries:
2 x e
2 x H+ (2 hydrogen atoms)

Question 12

What are the four reactions that take place in β-oxidation?

Answer 12

1. Oxidation
2. Hydration
3. Oxidation
4. Cleavage

Question 13

Describe reactions 1-3 of β-oxidation?

Answer 13

Reactions 1 to 3 involve a rearrangement:

• energy captured (2 redox reactions)
• the chemistry around the bond is altered so it can be
  cleaved in reaction 4

Question 14

Describe reaction 4 (cleavage) of β-oxidation?

Answer 14

Reaction 4 is a cleavage between the ⍺ and β carbons:
- acetyl-CoA released

• CoASH added to remaining carbon chain
• 2 carbon shorter fatty acyl-CoA enters next round

Question 15

What is the important equation to determine the number of rounds of β-oxidation and therefore determine the products generated?

Answer 15

Number of rounds = n(C)/2 - 1

C = the number of carbons of the fatty acid

Question 16

What does β-oxidation use: even or odd number of carbons in the fatty acids?

Answer 16

• β-oxidation uses fatty acids with an even number of
  carbons that are saturated (no double bonds)

Question 17

Stearic acid is an 18-carbon, saturated fatty acid. How many rounds of β-oxidation will occur to fully oxidize stearic acid, and what will be the net yield of this oxidation?

Answer 17

Number of rounds = n(C)/2 - 1

= 18/2 -1 = 8 rounds

8 rounds of β-oxidation:
8 NADH, 8 FADH2 and 9 acetyl-CoA

Question 18

What enzyme mobilised stored TAGs in adipose to be used as fuel?

Answer 18

• Hormone sensitive lipase cleaves TAGs to give three FFAs and glycerol which passively diffuse into the blood

Question 19

How are the mobilised FFAs transported in the blood to be used as fuel?

Answer 19

Bound to Albumin, a protein found in the blood that transports FFA’s in the aqueous environment.

Question 20

Do FFA’s need transport into the cells that will use them, also do they need a carrier inside the cell?

Answer 20

Yes, FFA need transport help across the cell membrane where it is used (not much detail so don’t think important)

Inside the cell, FFA’s bind to FABP = fatty acid binding protein which are barrel shaped to protect the FFA from the aqueous environment

This FFA can then be transported to the mitochondria within the cell where it can be oxidised