Fatty Acid Oxidation Flashcards
What is the most important form of fat storage, and why is it so important?
Triacylglycerol accounts for around 85% of fat stored in the body.
It is very efficient at storing fat, and stores much more energy than glycogen by both weight and volume.
What are the different sources of fat?
Liver → During the fed state, the liver can make and release fats in the form of lipoproteins, which are then taken up by adipose tissue
Blood → Free fatty acids bound to albumin circulate in the plasma (due to slightly soluble COO-). Can also circulate as triacylglycerol packaged in lipid membranes, cholesterol and protein ie. as lipoproteins. This prevents them clumping together and blocking blood vessels due to being hydrophobic.
Adipose tissue → The main site of fat storage
Skeletal muscle → Some types of muscle fibres contain fat droplets
What is the difference in function of hormone-sensitive lipase and lipoprotein lipase?
HSL → Acts on triacylglycerol in intracellular lipid droplets. The fatty acid is then released into the blood and another part of the tissue can take it up and use it as fuel. It is stimulated by exercise (adrenaline), the cold (noradrenaline) and fasting (low insulin).
LPL → Acts on triacylglycerol in lipoproteins circulating in the blood. LPL is attached to the capillary wall, catalyses the reaction when a lipoprotein passes, and then the fatty acid enters a tissue that needs it. The cell that secretes LPL may not receive all of the fatty acids that are released - it may not receive any of it either.
In which situations would adipose tissue and skeletal muscle secrete hormone-sensitive lipase and lipoprotein lipase?
Adipose + HSL → Adipose tissue wants to release fatty acids into the blood because another part of the body needs it as fuel.
Muscle + HSL → Muscle tissue wants to use the fatty acids as fuel
Adipose + LPL → Adipose tissue wants to take up fatty acids and store them
Muscle + LPL → Muscle tissue wants to use fatty acids as fuel
Why must fatty acids be esterified with CoASH?
Because fatty acids are hydrophobic, they can diffuse through the cellular membrane and into mitochondria, or travel via transporters.
This is bad because fatty acids are toxic, as they can dissolve other hydrophobic compounds and cause damage.
To trap fatty acids inside the cell and outside of mitochondria, they are esterified with CoASH to form Coenzyme A, CoA.
This forms a thioester bond and uses up 2 x ATP with the reaction, making it irreversible:
ATP → AMP + PPi
What are the steps involved in fatty acid (β) oxidation?
1 → Reduction
The fatty acyl-CoA is oxidised by fatty acyl-CoA dehydrogenase forming enoyl-CoA, reducing FAD to FADH2 in the process. This forms a double bond between the α and β carbons.
2 → Hydration
The double bond is hydrated using the enzyme enoyl-CoA hydrolase, forming hydroxy acyl-CoA. This adds an hydroxyl group onto the β carbon.
3 → Reduction
The hydroxy acyl-CoA is oxidised by hydroxy acyl-CoA dehydrogenase, reducing NAD to NADH in the process. This forms a double bond on the β carbon, meaning the α-β bond is weak enough to be cleaved in the next step.
4 → Cleavage (thiolysis)
The α-β bond is cleaved by thiolase, and this joins with CoASH to form acetyl-CoA. The fatty acid is now 2 carbons shorter.
This process repeats until there are only 2 Cs left, and these can be joined directly onto CoASH.
What are the equations for working out the number of acetyl CoAs and FADH2 + NADH produced in fatty acid oxidation?
acetyl CoA = number of carbons in FA / 2
FADH2/NADH = ( number of carbons in FA / 2 ) - 1
What happens to fatty acid oxidation during the fed state?
Brain → Neurons in the brain contain very low levels of thiolase, so they do not oxidise fatty acids. The brain will continue to use glucose as a fuel source.
Liver → Fatty acid oxidation is inhibited due to the increase in glycolysis and fatty acid synthesis.
Adipose tissue → Does not perform much FA oxidation, so no fatty acids are released into the blood.
Skeletal muscle → Fatty acid oxidation is inhibited due to glycolysis.
What happens to fatty acid oxidation during exercise?
Brain → only uses glucose for fuel
Adipose tissue → Releases fatty acids into the blood
Skeletal muscle → Increased FA oxidation due to increased FA supply (from adipose tissue releasing them)
What happens to fatty acid oxidation during fasting?
Brain → only uses glucose as fuel
Adipose tissue → Releases fatty acids into the blood
Skeletal muscle → Glycolysis is inhibited, so fatty acid oxidation increases
What happens to fatty acid oxidation during starvation?
Brain → Uses glucose as well as ketone bodies for fuel; the glucose that is used up is replaced by protein breakdown
Adipose tissue → Releases fatty acids into the blood
Skeletal muscle → Glycolysis is inhibited, so fatty acid or ketone bodies are used as fuel.
What are ketone bodies and how are they made?
Ketone bodies are made by the liver and can be used as an alternative fuel source, specifically by the brain during starvation.
2x Acetyl CoA → 2x CoASH + 4C ketone body
Cells only require aerobic conditions and mitochondria in order to use ketone bodies as a fuel, so most tissues can use them.
