LECTURE 18 - FATTY ACID BREAKDOWN Flashcards
where does FA breakdown happen?
in the mitochondrion
what is beta oxidation?
breakdown of FA to make acetyl CoA
where do those FAs to be broken down come from?
- uptake from circulation
- lipolysis from lipid storage droplets
- phospholipases, but this rarely happens
how can FAs get into the mitochondria?
long chains of FAs cannot cross the inner mitochondrial membrane
1. activation by CoA via acyl CoA synthetase
pyrophosphatase drives this reaction
generates high energy intermediate
keeps FA inside
2. coupling to carnitine via CPTI
this is the rate limiting step for beta oxidation
3. carnitive can now cross inside the mitochondrial matrix
4. FA is released into the matrix from cartinitine by CPTII
how is CPTI regulated?
rate limiting step of FA breakdown
inhibited by malonyl CoA, which is the first step of FA synthesis
so when you start making them you want to shut off the breakdown
malonyl CoA binds where acyl CoA should bind because of the similar CoA component
how does beta oxidation of saturated FAs happen?
step 1: dehydrogenation
this generates FADH2
step 2: hydration
step 3: dehydrogenation to make NADH
step 4: thiolic cleavage to make acetyl CoA
step 5: repeat reactions 1-4 to make more acetyl CoA until you get to the end of the chain
what does FADH2 feed back in?
this goes to the ETF: electron transfer flavoprotein
this joins back at the CoQ stage
how does beta oxidation of unsaturated FAs happen?
- dehydrogenation is replaced by isomerisation as the first step
- hydration
- dehydrogenation
- thiolic cleavage
- repeat
steps 3-5 are the same for unsaturated and saturated
there is no FADH2 produced when you do beta oxidation of an unsaturated FA
how does beta oxidation of polyunsaturated FAs happen?
for the unsaturation of the odd carbon there is no FADH2 produced
but for the unsaturation at the even carbon the FADH2 is normally produced
for each even unsaturation there is a cost of one NADPH
how does beta oxidation of odd chain fatty acids happen?
odd chain FAs are more rare than even chain FAs
step 1. normal beta oxidation until the last 3 carbons
the last 3 carbons are released as propionyl CoA
step 2. propionyl CoA (3C) is converted to succinyl CoA
step 3. succinyl CoA goes into the CAC
what are some branched fatty acids and where are those found?
phytanic acid and pristanic acid
branched FAs are very rare
they are found in milk
how are branched fatty acids broken down?
take chunks of 3 and 2 carbons
the 3C chunks will be made into propionyl CoA and the 2C chunks are Acetyl CoA
what are the 3 ketone bodies?
acetone
acetoacetate
beta hydroxybutyrate
when does ketogenesis happen?
in the liver mainly
during starvation
oxaloacetate is depleted and the CAC stops
the issue is that acetyl CoA does not transfer between tissues
what is ketogenesis?
ketone bodies serve as a shuttle for acetyl CoA to other organs
the heart and the brain reverse the thiolase reaction to make Acetyl CoA again
