Fatty acid transport, catabolism and anabolism Flashcards
How are fatty acids transported round the body?
Fatty acids bind to Human Serum Albumin where they are then transported to the outer membrane of the mitochondrion where they are activated
How are fatty acids activated?
The fatty acid is attached to ATP forming acyl adenylate (FA+AMP) and PPi
Via Synthetase, CoA–HS then attaches forming an acyl CoA and releasing AMP
How do fatty acids enter the mitochondria?
Acyl-CoA can cross the outer mitochondrial membrane
Carnitine acyltransferase 1 swaps CoA for carnitine
This means it can be transported via a translocase antiporter through the IMM
It is then swapped back to CoA in the matrix
How are fatty acids catabolised?
Through beta oxidation, 2 carbons are released at a time
What is the first step of beta oxidation?
Dehydrogenase oxidises the alpha and beta carbons leaving a double bond between them
The hydrogens are given to FAD+ making it FADH2
What is the second step of beta oxidation?
Hydratase and H2O leave the alpha carbon with two hydrogens and the beta carbon with H and OH attached
What is the third step of beta oxidation?
Dehydrogenase oxidises the beta carbon leaving a double bonded oxygen
The removed hydrogens convert the NAD+ into NADH + H+
What is the forth step in beta oxidation?
The bond between alpha and beta carbons are broken and HS-CoA is attached to the remaining strand
What are the products for beta oxidation?
For each cycle there is:
1xFADH2
1xNADH
1xAcetyl CoA (the last cleavage has two)
How do you calculate how many cycles a fatty acid takes to dissolve?
n cycles= (n carbons/2)-1
How many ATP does palmitic (18C) acid produces vs 3 glucose (18C)
Palmitic acid= 129 ATP
Glucose= 114 ATP
What is difficulty with poly unsaturated fat?
An additional isomerase enzyme is needed to convert the cis double bond into a trans double bond
What happens under starving conditions?
A higher levels of TG hydrolysis occurs, however when acetyl CoA builds up over the capacity of the TCA cycle. Thus Ketone bodies are made
How are ketone bodies produced
The last step of beta oxidation is reversed and three acetyl CoAs are joined together
How is Acetyl CoA exported into the cytoplasm? THIS IS A CYCLE
Acetyl CoA is joined with OAA to form citrate
Citrate travels across the membrane before splitting again
The OAA is reduced by NADH to form malate
Using NADP+ it is split into pyruvate and CO2 before crossing the membrane
Here it is joined with CO2 and the cycle repeats with replenished OAA
What is the purpose of fatty acid anabolism?
To convert Acetyl CoA back into palmitic acid
What is the initiation step for fatty acid synthesis?
Acetyl CoA is modified by Acetyl CoA Carboxylase
Acetyl CoA + ATP + HCO3- => Malonyl CoA + ADP + Pi + H+
What is the first step of fatty acid synthesis?
Through a condensation reaction malonyl/acetyl CoA-ACP Transacylase joins an acetyl group with the malonyl forming malonyl-ACP
What is the second step of fatty acid synthesis?
Beta Ketoacyl-ACP synthase joins the acetyl and malonyl causing a loss of CO2
Forming acetoacetyl-ACP
What is the third step of fatty acid synthesis?
The carbonyl group (=O) is reduced by NADPH and H+ to convert it into a hydroxyl group (beta ketoacyl- reductase)
What is the forth step in fatty acid synthesis?
The hydroxyl group is removed and is replaced by a C=C forming enoyl-ACP (dehydrase
What is the last steps of fatty acid synthesis?
The double bond is broken and reduced with NADPH and H+ forming a CH2 group
At this point the product is fed back into the cycle and it continues to add two carbons till it reaches 18
How are fatty acids transported to the adipose after synthesis?
If synthesised in the liver lipoprotiens will export TG to the other tissues
What are the 5 different types of chylomicrons/lipoproteins and how do they differ
Size decrease, density increase
VLDL- Very Low Density
IDL- Intermediate density
LDL- Low Density
HDL- High Density
How do the lipoprotein composition vary?
Apoprotien- increase
Triglycerides- rapid decrease
Choesterol- increase in LDL
Phospholipids- no changes
What is the life span for each lipoprotein?
VLDL- mins=hours
IDL- mins=hours
LDL- 3 days
HDL- 3,6 days
What is hyperlipidaemias?
There is a defect in the LDL-R gene
This means the receptors are faulty
In heterozygous people there’s double the amount of normal plasma LDL
In homozygous people plasma LDL >6000mg/L
