Lecture 4 - oxidation of lipids Flashcards
who was Franz Knoop? and when did he conduct his experiment?
- published in 1904
- Fed fatty acid labelled at the methyl end with phenyl groups to dogs
Why ere phenyl groups used in Franz Knoops experiments?
phenyl group cannot be degraded, type of marker within the human body
What did the experiment find on examination of the urine?
From odd chain lengths… he always found benzoate
From even length chains, he always found phenyl acetate
What did the experiments determine?
Where there is a B carbon it can be oxidised .
Then the bond between a and B carbons can be broken
Which is the B carbon in fatty acids?
C-3 from the carboxyl end
What are the 3 stages of B - oxidation of fatty acids?
- Activation
- Transport
- Oxidation
What happens in the ‘activation’ stage?
Attach the fatty acid to the Coenzyme A to form Acyl- CoA
Why is CoA attached?
Ensures that as the subsequent reactions can occur because it has the negative delta G of reaction
Where does this activation occur?
At the outer surface of the mitochondria
Which enzyme catalysed the activation?
Acyl- CoA synthetase
What are the products of the activation reaction
- Acyl - CoA
- AMP
- pyrophosphate
What is the reason for the cell creating pyrophosphate?
When pyrophoshosphate is hydrolysed we get 2 inorganic phosphates, the reaction is forced more towards the right .
Which enzyme converts pyrophosphate into 2 inorganic phosphates?
pyrophosphatase
Where is acyl-Coa taken to , to be metabolised?
The mitochondria
What intermediate transports Acyl- CoA into the matrix of the mitochondria?
carnitine
How does the overall process of this movement work?
Overall process does not transport acyl-CoA into the mitochondria. The overall process uses the carnitine to carry the acyl through into the matrix. Acyl – Carnitine goes in , in exchange for carnitine coming out. The Co-A outside , stays outside. Only the Acyl part that moves
Where does the Acyl group get attached to on the Carnitine?
gets attached to the OH group, releases the CoA
How are the fatty acids oxidised?
- 2 carbon unit removed by a 4 step process
Summary of the 4 step process for oxidation?
- Oxidation
- Hydration
- Oxidation
- Thiolytic cleavage
What is the enzyme in the first oxidation step?
Acyl - CoA dehydrogenase
What is the reaction occurring in the first oxidation step?
- Double bond formed between A and B
- Dehydration reaction , removing 2 hydrogens. FAD takes the hydrogens
What is the enzyme in the second oxidation step ( hydration)
Enoyl- CoA hydratase
What is the product formed in the first oxidation step?
- Trans - Enoyl CoA
What is the product formed in the second oxidation step?
Hydroxy- acyl -CoA
What is happening in the second oxidation step?
OH added to the molecule
What is the name of the enzyme in the third step of the oxidation reaction?
B- hydroxylacyl - CoA dehydrogenase
What is the product of the third step of the oxidation reaction?
B - Ketoacyl - CoA
What is happening inn the third step of the oxidation reaction?
Removal of two Hydrogens. Taken uo by NADH and H
What is the final product of the oxidation reaction
Acetal CoA and Acyl - CoA
What is the name of the enzyme in the fourth step of the oxidation reaction?
acyl-coA acetyltransferase
What is happening in the final stage of oxidation reaction?
Breaking and reforming the thirster bond
