Metabolism 3, fatty acid oxidation (Miss Dawson) Flashcards
What are the biological roles of lipids ?
Forming membranes, storing energy (storage fats), hormones etc.
What is the most important form in which fat is stored in mammals ?
Triacylglycerol (TAG), an ester derived from glycerol and three fatty acids, that account for approximately 85% of energy storage in mammals. Tag is the most common fat in food and can store much more NRG that glycogen (by weight and volume).
When is fat oxidation important ?
NOT after eating ! Excess glucose could be toxic and the body can only store limited amounts of glycogen.
In the fasting state, the use of fats by most tissues increases, leaving glucose for other tissues. Fats can also be used to make ketone bodies during starvation for the brain.
During exercice, both glucose and fat are are mobilized for muscle.
What are the main sources of fat in the human body ?
Adipose tissue is the main site of fat storage.
The Liver can make fat and release into the blood.
Fat circulates in the plasma as free FA bound to albumin, or as TAG in lipoproteins.
Some types of muscle fibre contain fat droplets.
What is hormone sensitive lipase ?
HSL is an enzyme that hydrolyses TAG in intracellular lipid droplet (thus releasing fats). It is stimulated by adrenaline (exercise), noradrenaline (cold) and low insulin (fasting).
What is lipoprotein lipase ?
LPL is an enzyme that hydrolyses TAG into 3 FAs and one glycerol molecule. It is secreted by tissues such as muscle and adipose tissue. FAs can be used as NRG or stored in adipose tissue.
Where does FA oxidation happen ?
In the mitochondrion.
What are the steps of beta oxidation ?
- The FA binds to acyyl-CoA vie the long chain fatty acyl-CoA ligase. ATP is hydrolyzed to AMP
- Fatty acyl-CoA is reduced to enoyl CoA by fatty acyl-CoA dehydrogenase. 1 FADH2 is prodoced.
- Enoyl CoA is hydrated (H2O gained) and converted to hydroxy-acyl CoA by only CoA hydratase.
- Hydroxy-acyl CoA is reduced to keto-acyl CoA by hydroxy-acyl CoA dehydrogenase. NADH is produced.
- Keto-acyl CoA is thiolysed into a now shorter fatty acyl-CoA and a and an acetyl CoA molecule by thiolase.
What is th NRGtic yield of beta oxidation ?
The binding of the FA to acyyl-CoA vie the long chain fatty acyl-CoA ligase requires 2 ATPs. For every cleavage of fatty acyl-CoA into a 2C shorter fatty acyl-CoA, 1 FADH2, 1 NADH2 and one acetyl CoA is produced.
NADH2 = 1.5 ATPs in respiratory chain
NADH = 2.5 ATPs in respiratory chain
Acetyl CoA = 5 ATPs in Krebbs cycle
Thus if n the number of carbon of the initial fatty acyl-CoA, the total yield of ATPs = [(n/2)5 + ((n-1)/2)1.5 + ((n-1)/2)*2.5] - 2
How can cells be limited in their rate of beta oxidation ?
If they have few mitochondria or if the blood supply (O2) is low.
Why can’t neurons oxidize fats ?
Because they have very low levels ofthiolase.
During fasting or extreme exercise, what can happen to the acetyl-CoA produced by beta oxidation ?
It can be converted into ketone bodies (a very water soluble 4C molecule) as an alternative fuel for the brain.
How are beta oxidation levels in the key organs in the fed state ?
Sk muscle: FA oxidation is inhibited due to increase in glycolysis
Adipose tissue: not much FA oxidation
Liver: FA oxidation is inhibited due to glycolysis and fatty acid synthesis
Small intestine: fat from digestion enters lump as lipoproteins
How are beta oxidation levels in the key organs during exercise ?
Sk muscle: FA oxidation increases as FA supply increases
Adipose tissue: releases FA into circulation
How are beta oxidation levels in the key organs in the fasted ?
Sk muscle: glycolysis inhibited and fats used
Adipose tissue: FA released into circulation