Fatty Acid Metabolism- Oxidatoin
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- Overview of Fatty Acid Breakdown
- sequential removal of 2C as Acetyl coA to feed into TCA Cycle
-
First stage to prep for Oxidation
Creation of Acyl-CoA
i.e. activation, a fatty acid connected to a COA -
Fatty acids must get activated to CoA derivative before oxidation, happens in cytosol
1=fatty acid + ATP~acyladenylate and PPI (cleaved to drive rxn)
acyl adenylate + CoA~Acyl CoA and AMP released
Now fatty acid activated in acyl Co A form and ready to head to matrix for oxidation
Different enzymes catalyze this for different length fatty acids -
Get loaded Acyl CoA into matrix
If more than 14C needs help -
Carnitine shuttle
1=Outside matrix Carnitine takes acyl group form COA (CAT1=carnatine acyl trasferase)
2=acyl carnatine taken across mito membrane into matrix (translocase)
3=Acyl carnatine gives acyl group back to CoA inside matrix (CAT 2)
*major regulated step in oxidation is the transfer into matrix by CAT1* -
Fatty Acid oxidation
4 steps -
oxidation
hydration
oxidation
cleavage - Oxidation
- beta hydroxyacly CoA dehydrondenase removes H and drops on NAD
- Hydration
- Enoyl Co A hydratase adds H20
- Cleavage
-
acyl-CoA acetyltransferase releases Actyl Co A
now can be fed into TCA cycle - Interaction with Coenzyme Q
- the FAD from the first oxidation step here can drop the e- on Coenzyme Q which is a complex 2 in the ETC
-
Monounsaturated fatty Acids
Enoyl Co A Isomerase -
our machinery deals with cis double bonds
This enzyme changes cis to trans so we can oxidize them -
poly unsaturated fatty acids
2 Enzymes to convert cis to trans -
enoyl-CoA isomerase does the first cis, same as with monounsaturated
2,4-dienoyl-CoA reductase - Odd Chain Fatty Acids
-
Can be dealt with like normal, until the end where there are only 3 remaining carbons (Propionyl-CoA)
Solution to this problem is the addition of another carbon
􀂃 Step 1: propionyl-CoA carboxylase w/ biotin adds another carbon from HCO3- to make D-methylmalonyl-CoA
􀂃 Step 2: an epimerase makes changes shape of molecule
􀂃 Step 3: methylmalonyl-CoA mutase w/B12 makes succinyl-CoA
􀂃 Step 4: succinyl-CoA synthetase removes CoA and allows it to continue through TCA cycle - Regulation of Fatty Acid Oxidation
- Malonly C0A=inhibits carnitine palmitoyl transferase (CAT-1) which takes malonyl into matrix