Beta oxidation is the process by which fatty acids are broken down in the mitochondria to generate acetyl-CoA. This involves four steps - dehydrogenation, hydration, oxidation, and cleavage - that occur on the beta carbon of fatty acyl-CoA molecules. Each cycle shortens the fatty acyl-CoA by two carbons and generates acetyl-CoA, FADH2, and NADH. This process is repeated until the fatty acid is completely broken down. Unsaturated fatty acids require additional enzymes for isomerization and reduction to allow all steps of beta oxidation to occur. Overall, beta oxidation generates energy in the form of ATP.

1. Beta Oxidation and its
Bioenergetics.
BY: TUBA TAHIR

2. Beta Oxidation:
It can be defined as oxidation of fatty acids on beta carbon.
Beta oxidation is a metabolic process involving multiple steps by
which fatty acid molecules are broken down to produce energy.
More specifically, beta oxidation consists in breaking down long fatty
acids that have been converted to acyl-CoA chains into progressively
smaller fatty acyl-CoA chains.
This process generates acetyl-CoA which enters the citric acid cycle,
and NADH and FADH2,which are co-enzymes used in the electron
transport chain.

3.  Where does Beta Oxidation
Occur?
Beta-oxidation is the catabolic process by which fatty acid molecules
are broken down,
1-In the cytosol in prokaryotes.
2-In the mitochondria in eukaryotes.
Beta oxidation goes on until two acetyl-CoA molecules are produced
and the acyl-CoA chain has been completely broken down.

4. Activation of fatty acids in
cytosol:
The fatty acid protein transporters allow fatty acids to cross the cell
membrane and enter the cytosol. The enzyme fatty acyl-CoA
synthase adds a CoA group to the fatty acid chain, converting it to
acyl-CoA.
This reaction occurs in two steps and require ATP and coenzyme A
and magnesium.
Fatty acids reacts with ATP to form acyl adenylate which then
combine with coenzyme A to produce acyl-CoA.

5.  Transport of acetyl CoA into
Mitochondria:
If the acyl-CoA chain is short, it can freely diffuse through the
mitochondrial membrane.
If the acyl-CoA chain is long, it needs to be transported across the
membrane by the carnitine shuttle.
For this, the enzyme carnitine acyltransferase 1 bound to the outer
mitochondrial membrane and converts the acyl-CoA chain to an
acylcarnitine chain.
Once inside the mitochondria carnitine acyltransferase-2 bound to
the inner mitochondrial membrane converts the acylcarnitine back
to acyl-CoA. At this point, acyl-CoA is inside the mitochondria and
can now undergo beta oxidation.

6.  Two high energy phosphate are utilized. Since, ATP is converted
to pyro phosphate. The biochemistry of whole reaction is shown
in figure.

7. Oxidation of Fatty acids:
It involves three stages such as:
1- Beta - oxidation. (Oxidation of fatty acid on beta carbon).
2- Oxidation in citric acid cycle. ( the acetyl groups of acetyl-CoA are
oxidized to CO2 in citric acid cycle).
3- Phosphorylation of ADP to ATP. (NADH and FADH electron carrier
donates electrons to mitochondrial respiratory chain. They pass
electrons to oxygen).

9. Steps in beta Oxidation process
of saturated fatty acids:
Beta oxidation takes place in four steps:
1-Dehydrogenation.
2-Hydration.
3-Oxidation.
4-Cleavage.
Each step is catalyzed by a distinct enzyme.

10.  Overview of Beta Oxidation
Process:
Each cycle of beta oxidation process begins with an acyl-CoA chain
and ends with one acetyl-CoA, one FADH2, one NADH and water.
The acyl-CoA chain becomes two carbons shorter.
This cycle is repeated until two acetyl-CoA molecules are formed as
opposed to one acyl-CoA and one acetyl-CoA. Let us discuss the
four steps of beta oxidation in detail.

12. 1-Dehydrogenation:
In the first step, acyl-CoA is oxidized by the enzyme acyl CoA
dehydrogenase. A double bond is formed between the second and
third carbons (C2 and C3) of the acyl-CoA chain entering the beta
oxidation cycle; the end product of this reaction is trans-enoyl-CoA.
This step uses FAD and produces FADH2, which will enter the citric
acid cycle and form ATP to be used as energy.

13. 2-Hydration:
In the second step, the double bond between C2 and C3 of trans-Δ2-
enoyl-CoA is hydrated, forming the end product beta hydroxy acyl
CoA.
This reaction is catalyzed by another enzyme enoyl CoA hydratase.
This step requires water.

14. 3-Oxidation:
In the third step, the hydroxyl group in C2 of beta hydroxy acyl CoA
is oxidized by NAD+ in a reaction that is catalyzed by 3-hydroxyacyl-
CoA dehydrogenase.
The end products are beta ketoacyl CoA and NADH + H. NADH will
enter the citric acid cycle and produce ATP that will be used as
energy.

15. 4-Cleavage:
In this step, beta ketoacyl CoA is cleaved by a thiol group of another
CoA molecule.
The cleavage takes place between C2 and C3; therefore, the end
products are an acetyl-CoA molecule and an acyl-CoA chain two
carbons shorter than the original acyl-CoA chain that entered the
beta oxidation cycle.

16. Beta oxidation Cycle:

17.  Bioenergetics of beta Oxidation:
1-Four beta oxidation steps are repeated to yield acetyl-COA and
ATP. Here one molecule of acetyl-CoA ,two pair of electrons and four
pair of protons are removed. It shortens chain by two carbons.
2-In next step, one acetyl-CoA unit is removed it further oxidizes one
molecule of palmitoyl-CoA to eight molecule of acetyl-CoA.
3-Each molecule of FADH2 donates a pair of electrons, and generates
1.5 molecules of ATP during transfer of each electron pair to O2.
4-Each molecule of NADH delivers a pair of electrons to
mitochondrial NADH dehydrogenase.it forms 2.5 molecules of ATP.
Overall reaction is shown next.

21.  Beta Oxidation of unsaturated fatty
acids:
Beta Oxidation of unsaturated fatty acids poses a problem since the
location of a cis bond can prevent the formation of a trans bond. The
enzyme Enoyl CoA hydratase cannot act on it.
These situations are handled by an additional two enzymes,
1-Isomerase.
2-Reductase.

22. Oxidation of monounsaturated
fatty acids:
Oleate is 18 carbon monounsaturated fatty acids. It has cis double
bond C-9 and C-10.
In first step, oleate is converted into oleoyl CoA.
Oleoyl CoA undergoes three passes through fatty oxidation cycle to
yield 3 molecules of acetyl CoA and results in the formation of 12-
carbon fatty acyl-CoA with a cis double bond. This product is known
as cis-Δ3-Dodecenoyl-CoA.
The above product formed has a cis double bond and cannot serve
as a substrate foe enoyl CoA hydratase. Thus by the action of Δ3,Δ2-
enoyl-CoA isomerase, cis-Δ3-Dodecenoyl-CoA is converted to trans-
Δ2-Dodecenoyl-CoA.

23. Now enoyl-CoA hydratase converts it into corresponding trans-2-
dodeocoyl-CoA.
Trans-Δ2-Dodecenoyl-CoA, now is acted upon by the enzymes
of beta oxidation pathway in five continuous cycles to yield
another 6 molecules of acetyl CoA.

24.  Oxidation of Polyunsaturated fatty
acids:
Linolenic acid is an unsaturated fatty acid with two cis double bond.
It undergoes three cycles of beta oxidation to yield three molecules
of acetyl CoA along with a 12 carbon chain fatty acyl-CoA with
configuration cis-Δ3,cis-Δ6
Since the configuration is wrong so it is now acted upon by the
enzyme 2,4-dienoyl CoA-reductase to form trans-Δ3 fatty acyl-
CoA which on further action by enoyl-CoA isomerase gives trans-
Δ2 fatty acyl-CoA.
The overall result is conversion of linoleate to nine molecules of
acetyl-CoA.

25. Oxidation of
Polyunsaturated
Fatty Acid.
o Conversion of
linoleate to 9 acetyl-
CoA.