Fatty Acids as a Fuel Molecule

Question 1

describe the process of delivery of fatty acids for fuel

Answer 1

from the diet of the liver: lipoproteins and LPL (lipoprotein lipase)
OR
from storage in the adipose tissue:
- adipose tissues do not make lipoproteins
- adipose lipas cleaves TAGs to give three FFAs and glycerol
- need to transport to tissues in blood then enter cells (FFA non-polar)

• Glycerol goes to the liver and the FFAs are picked up by Albumin in the blood to make Albumin-FAA, where it then travels to the tissues
  - albumin has binding pockets that are hydrophobic for FAA
• transported across the cell membrane by a passive transporter
• FABP: fatty acid binding protein binds and allows it to be in aqueous solution again - sits inside a barrel in hydrophobic non-polar environment
• once it is in the cells we can think of it as a fuel molecule

Question 2

describe the process of fatty acid activation

Answer 2

• fatty acids are activated before beta-oxidation
• occurs before the fat acid enters the mitochondria
• activated by attachment to CoA to make a fatty acyl-CoA
• energy to add CoA from hydrolysis of ATP to AMP (energy equivalent of 2ATP)

Reaction:
FFA + ATP + CoA-SH –> Fatty acyl-CoA + AMP + 2P
the enzyme Acyl-CoA synthetase facilitates this reaction

Question 3

describe where different reactions occur in the mitochondria

Answer 3

Matris:
- citric acid cycle
- beta-oxidation
- PDH

Inner membrane:
- electron transport chain

Question 4

describe the process of transporting fatty acids into the mitochondrial matrix

Answer 4

the fatty acyl-CoA must pass through two membranes
- outer membrane: fatty acyl-CoA carrier, can go through with no problems
- inner membrane: requires the conversion to fatty acyl-carnitine and then once it is through the other side the reaction is reversed (goes the other way to make fatty acyl-CoA again)
Reaction:
fatty acyl-CoA + carnitine <–> fatty acyl-carnitine + CoA-SH
- facilitated by carnitine acyltransferase
- reversible reaction

Question 5

describe the overall process of beta-oxidation

Answer 5

• in mitochondria matrix
• beta-oxidation uses fatty acids with an even number of carbons that are saturated (no double bonds)
• no ATP is directly made in beta-oxidation
• energy released in beta-oxidation is transferred to the coenzymes NAD and FAD
• the carbon chain is cut into 2 carbon pieces
  The produce of beta-oxidation, acetyl-CoA, is further oxidised in the citric acid cycle

Question 6

describe reactions 1, 2, and 3 of beta oxidation

Answer 6

1. normal carbon chain, single bonds.
   - undergoes oxidation, and FAD is reduced to FADH2
   - double bond is made between carbons (the two H’s transferred to FAD)
2. normal carbon chain but double bond between carbons now
   - undergoes hydration, and water is used to break the carbon double bond
   - carbon single chains, but hydroxyl group coming off one of the carbons
3. carbon single chains, with a hydroxyl group on one of the carbons
   - undergoes oxidation, NAD+ is reduced to NADH, H+
   - lose two hydrogens and the carbon with the hydroxyl group now has a double bonded oxygen on it

involve a rearrangement:
- energy is captured (two redox reactions)
- the chemistry is altered so it can be cleaved in reaction 4

Question 7

describe the role of FAD

Answer 7

FAD: flavin adenin dinucelotide
- derived from Riboflavin (vitamin B2)
- a coenzyme required by some enzymes that catalyse redox reactions (including fatty acid oxidation, citric acid cycle)
- flavin coenzymes are tightly bound to the protein with which they interact (flavoproteins) - whereas with NAD+ its free in the matrix and only associated with the enzyme when the reaction is happening
- undergoes two election reduction (accepts two reducing equivalents)
- FAD (oxidised form) to FADH2 (reduced form) - which carries 2H+, 2e-

Question 8

describe reaction 4 of beta-oxidation

Answer 8

the cleavage of the bond between the alpha and beta carbons:
- acetyl-CoA is released
- CoASH added to remaining carbon chain
- 2 carbon shorter fatty acyl-CoA enters the next round

Question 9

what is the general rule for how many rounds of beta-oxidation are needed?

Answer 9

rounds = n(C)/2 - 1

for each round of beta-oxidation: 1NADH + 1FADH2 + 1 acetyl-CoA
and some heat
overall, energetically favourable