FATTY ACID OXIDATION

Transcript by dr. JM Source : Osmosis

Disclaimer : this transcript helps you with osmosis video with the same title, to get

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Our bodies are capable of surviving without food for long period of time, up to two

weeks.

The reason we can do this is that we can store our dietary fuels and break them down

when we need them to make energy in the form of adenosine triphosphate or ATP.

Fat is one of the most important ways we store energy.

And the term fat burning actually refers to fatty acid oxidation, in fact if two

individuals were stranded in the antis mountain with no food, the person with more fat

content would survive longer, yet another reason to avoid working out.

What makes fat such a great source of energy are the fatty acids which are the

simplest form of fats composed of long chains of carbon and hydrogen, the transfer of

electrons in the form of hydrogen molecules from these fatty acids to set a molecules

can then be used to generate ATP. Fatty acids oxidation primarily takes place in the

mitochondria of the heart, skeletal muscle, and liver cells. Before we can oxidize fat it

needs to be moved from storage sites to the cells that can use it.

Fat is stored in adipocyte or fat cells is trycliceride which are three fatty acids attached

to a glycerol molecule. Tryglyceride can be broken down by the enzyme hormone

sensitive lipase into three fatty acids and glycerol.

So if you’re starving in the antis, first your blood glucose level falls and in response

the pancreas secretes a hormone called glucagon which increases the activity of

hormone sensitive lipase and increases the breakdown of tryglicerides.

Now, the free fatty acids can leave the fat cells and enter the bloodstream where they

bind to a protein called albumin.

Albumin carries the fatty acids to target cells like liver cells that are capable of fatty

acid oxidation.

First, the free fatty acid dissociate from albumin and difuses into the cell. Once inside

the cell a cytosolic enzyme called fatty Acyl-CoA synthetase adds a coenzyme A

(Co A) molecule to the end of the fatty acids turning it into a metabolic reactive fatty

acyl coA. These process requires two atp molecules. So takes a little energy to make

energy. But it’s totally worth in the end.

Now, the mitochondria is composed of two membranes, an outer membrane and an

inner membrane with the small space in between and the mitochondrial matrix at the

core. The enzymes required for beta oxidation are located in the mitochondrial matrix,

however the fatty acids can’t cross the inner mitochondrial membrane when co A is

attached to it. To get around this problem we need to free the Co A from the fatty

acids, an enzyme within the outer mitochondrial membrane called carnitine

acyltransferase 1 or Cat1 replaces the CoA with a carnitine making fatty acyl-carnitine

and a free co A both of which can easily cross the inner mitochondrial membrane then

along the inner mitochondrial membrane another enzyme called carnitine

acyltransferase 2 or Cat2 substitute carnitine and CoA back, therefore regenerating

fatty acyl co A and free carnitine which is now within the mitochondrial matrix. This

whole slick process is called the carnitine shuttle.

Carnitine can cross the inner mitochondrial membrane by itself, so it can go back to

the outer membrane to meet the next incoming fatty acids. We can also get more

carnitine from our diet, mainly meat products.

Finally, the carnitine shuttle can be regulated by product of fatty acid synthesis called

Malonyl Co A which specifically inhibit Cat 1, slowing down fatty acids oxidation.

Afterall you don’t wanna make and break fatty acids at the same time.

Okay, so fatty acid chains can vary in lenght, we’ve got short, medium, long and very

long atty acids but the process of fatty acid oxidation is the same for any lenght, we’ll

explain fatty acid oxidation within example of a long chain fatty acids the 16 carbon

long palmitoyl coa. The enzymatic modifications that take place in fatty acid

oxidation happen on the second and third carbon of the chain, also called the alpha

and beta carbon respectively, each of those carbons enters the fatty acid oxidation

with two hydrogen bound to it.

First, an enzyme called acyl-CoA dehydrogenase removes one hydrogen from the

second carbon and one hydrogen from the third. The same enzyme then gives those

two hydrogens to nearby flavin adenine dinucleotide molecule or FAD making

FADH2 and converting the palmitoyl Co A to ENOYL CoA in the process.

Enoyl Co A has one hydrogen on each of the afferent beta carbons

This is the first oxidation step.

Next, an enzyme called enoyl-coa hydratase transfers a hydroxyl group which is an

oxygen linked to the hydrogen from a water molecule onto the beta carbon of

enoylcoa making beta hydroxyacyl coA.

The second oxidation step involves a similar hydrogen transaction mediated by

another dehydrogenaze called beta hydroxyacyl dehydrogenase.Beta hydroxyacyl

dehydrogenase removes two hydrogen from the beta carbon and transfers one of them
to a nicotinamide adenine dinucleotide molecule or NAD+ making NADH and beta

ketoacylcoA in the process and releasing the other hydrogen and because this

oxidation step occurs at the beta carbon. Fatty acid oxidation is also sometimes called

beta oxidation

Finally, an enzyme called beta ketothiolase cleaves those two alpha and beta carbons

off the fatty acids chain making it two carbon acetyl co A molecule in the process this

leaves us with a fourteen carbon fatty acid chain that can enter another cycle of beta

oxidation. So, the longer the fatty acid chain the more cycles and the more energy we

make, and in one cycle of beta oxidation we make 1 NADH, 1FADH2, and 1

acetylCoA.

NADH and FADH2 are now full of electrons and they can enter the mitochondrial

pathway called the electron transport chain where those electrons can be used to make

ATP, 1 NADH molecule makes roughly 3 ATP, well 1 FADH2 molecule makes

roughly 2 ATP, on the other hand acetyl coa can enter the citric acid cycle which is

another metabolic pathway in the mitochondria acetyl coA to make more NADH and

FADH2 which then enter the electron transport chain yielding a total of 12 ATP per

acetyl CoA. So, from a sixteen carbon palmitoyl coA molecule we make a total of 7

NADH, 7 FADH2, and 8 Acetyl-CoA molecules, if we calculate the total ATP yield

we make 131 ATP but remember, we consume 2 ATP when we first activated fatty

acetyl CoA. So, per palmitoyl Co A we make a net worth of 129 ATP molecules.

That’s a lot of ATP. Eh, told you it was worth it. Now, that’s straight forward enough

for a fatty acid that has an even number of carbons but the oxidation of the fatty acids

within odd number of carbons can be somewhat different.

So, let’s say we’re dealing with 13 carbon fatty acids, initially the process of

oxidation goes exactly the same until we reach a three carbon fragment called
propionyl coa, this is when it gets a bit awkward for the prototypical oxidation

enzyme, so to get the job done we’ll need another three enzymes to break it down, 3

reactions for the 3 carbon molecule if you like, so first an enzyme called propionyl

coa carboxylase adds a carboxyl group to the propionyl CoA making methylmalonyl

co A. This enzyme requires three co factors which can be remembered with a handy

mneumonic A B C, A is for ATP, B for Biotin or vitamin B7, and C for carbon

dioxide which is the carboxyl group source in these reaction. Next, an enzyme called

methylmalonyl CoA mutase rearranges the carbons on methylmalonyl co A to make

succinyl Co A. These enzyme requires vitamin B12 as a co factor succinyl co A can

then enter the citric acid cycle or it can be used for the synthesis of heme which is the

oxygen binding element in hemoglobin.

Finally, for really long fatty acid molecules that are 22 carbons long or longer.

Specific organelles called peroxisomes maybe needed, peroxisomal oxidation works

in the same way as mitochondrial oxidation, but it just has different enzymes that are

capable of degrading the long fatty acid chain until its under 22 carbons and then the

fatty acids are sent back to the mitochondria to take over.

All right, so as a good recap.

Fatty acids are one of the main sources of energy in the body, especially during the

fasting state

Fatty acid oxidation occurs in three steps

1. Activation then 2. transport through the carnitine shuttle and finally 3. beta

oxidation in mitochondrial matrix