All types of oxidation of fatty acids are covered in this presentation which includes alpha, beta, omega and peroxisomal oxidation

4. Fatty acids are oxidized by most of the tissues in
the body.
However, brain, RBCs & adrenal medulla cannot
utilize fatty acids for energy requirement.

5. α- oxidation ω-oxidation
Fatty acids are oxidized by following
pathways…

6. β-Oxidation of fatty acids
Most of the fatty acids in the body are oxidized
by β-oxidation.
It is defined as, oxidation of fatty acids at β-
carbon atom.
This results in sequentially removed of 2 carbon
units, acetyl CoA.

7. β-oxidation
proper (in
mitochondrial
matrix)
Transport of
fatty acids
into
mitochondria
Activation
of fatty
acids
(in cytosol)
Steps in β-Oxidation of fatty
acids

8. Activation of fatty acids
The 1st step in the oxidation of fatty acid is
activation of free fatty acids.
It is must to activate fatty acid before being
catabolized.
In this reaction, fatty acid is converted to acyl
CoA in the cytosol by the enzyme thiokinase (acyl-
coA synthetase) in presences of ATP, coenzyme-A.
The reaction occurs in two steps.
Three different thiokinase have been identified
to activate long chain, medium chain and short
chain fatty acids.

9. R-CH2-CH2-CH2-C-AMP
O
=
ATP
PPi
Mg++
Fatty acid
Acyl-CoA
Acyl-CoA synthetase /
CoA-SH
R-CH2-CH2-CH2-C-O-
O
=
R-CH2-CH2-CH2-C-SCoA
O
=
Acyladenylate
AMP
thiokinase
2Pi
pyrophosphatase

10. Transport of acyl-CoA into Mitochondria
The inner mitochondrial membrane is impermeable
to fatty acids.
A specialized carnitine carrier system operates
the transport of activated fatty acids from
cytosol to the mitochondria.
Acyl group of acyl-CoA is transferred to carnitine by
the carnitine acyltransferase I (CAT-I).
The acyl-carnitine is transported across the membrane
to mitochondrial matrix by a specific carrier protein.
carnitine acyltransferase II (CAT-II) converts acyl-
carnitine to acyl-CoA.
Carnitine is returns to the cytosol to reuse.

12. Each cycle of β-oxidation liberates two
carbon unit-acetyl CoA.
It starts from carboxylic end.
It occurs in a sequence of four reactions.
Oxidation
Hydration
Oxidation
cleavage

13. Oxidation- Acyl-CoA undergoes dehydrogenation
by an FAD-dependent enzyme, acyl-CoA
dehydrogenase to give enoyl CoA.
Hydration- enoyl-CoA hydratase brings about
the hydration of the double bond to form
β–hydroxyacyl-CoA
Oxidation-β–hydroxyacyl-CoA dehydrogenase
catalyses 2nd oxidation & generate NADH.
Cleavage-β-ketoacyl-CoA which is synthesized in
above reaction is cleave to produces 2 carbon
unite acetyl-CoA and acyl-CoA(2 C less) by the
enzyme β-ketoacyl CoA thiolase

14. Inner Mitochonrial Membrane
R-CH2-CH2-CH2-C-O-
O
=
R-CH2-CH2-CH2-C-SCoA
O
=
R-CH2-CH2-CH2-C-SCoA
O
=
R-CH2-CH=CH-C-SCoA
O
=
R-CH2-CH -CH2-C-SCoA
OH
-
O=
R-CH2-C-CH2-C-SCoA
O O
=
=
R-CH2-C-SCoA
O
=
CH3-C-SCoA
O
=
ATP
AMP+PPi
Mg++
CoA-SH
FAD
FADH2
H2O
NAD+
NADH+H+
Carnitine Transporter
Fatty acid
Acyl-CoA
Acyl-CoA
Trans Enoyl-CoA
3-hydroxy acyl-CoA
3-keto acyl-CoA
Acetyl-CoAAcyl-CoA
Acyl-CoA
synthetase
Acyl-CoA
dehydrogenase
Trans enoyl-CoA
hydratase
3-hydroxy acyl-CoA
dehydrogenase
Thiolase
CoA-SH
©

15. Summary of β-oxidation of palmitoyl CoA
Palmitoyl-coA
CO-S-coA
CH3
α
β
ω
1
2
3
4
5
6
7
8
9
10121416
15 13 11
8 Acetyl-coA
CH3-CO-SCoA
7 NADH+H+
7 FADH2
7 Cycles of
β-oxidation
NADH+H+
FADH2
Electron Transport
Chain (ETC)
ATPADP+Pi
2H++½O2 H2O
CO2
TCA Cycle

16. Energetics of β-oxidation.
The ultimate aim of β-oxidation is to generate
energy.
Palmitoyl CoA undergoes 7 cycles of β-oxidation
to give 8 acetyl CoA, 7FADH2, 7NADH+H.
Acetyl CoA enter TCA to get complete oxidation
into CO2 , H2O and ATP.
The energy generated from the complete
oxidation of palmitic acid is given below….

17. 8 Acetyl CoA X 10
7 FADH2 X 1.5
7 NADH X 2.5
Total ATP
80 ATP
10.5 ATP
17.5 ATP
108 ATP
ATP used -2 ATP
Net ATP 106 ATP
Energetics of β-oxidation.

18. The availability of free fatty acid (FFA).
Levels of FFA is controlled by
glucagon:insuline ratio.
Glucagon increases FFA levels
Insulin decreases FFA levels.
CAT-I regulate the entry of fatty acids
into mitochondria.
Malonyl CoA inhibits CAT-I activity.

19. SIDS — a disorder due to blockade in
beta-oxidation
The sudden infant death syndrome (SIDS) is
an unexpected death of healthy infants, usually
overnight.
The real cause of SIDS is not known.
It is now estimated that at least 10% of SIDS
is due to deficiency of medium chain acyl CoA
dehydrogenase.
The enzyme defect has a frequency of 1 in
10,000 births.

20. Jamaican vomiting sickness
It is characterized by…
Severe hypoglycemia,
vomiting,
convulsions,
coma and
death.
It is caused by eating unripe ackee fruit which
contains an unusual toxic amino acid, hypoglycin A.
This inhibits the enzyme acyl CoA dehydrogenase
and thus beta-oxidation of fatty acids is blocked,
leading to various complications.

21. The odd chain fatty acids are oxidised in the
same manner as even chain fatty acids.
At the end of final oxidation cycle, a 3 carbon
fragment propionyl CoA left behind, instead of
acetyl CoA.
The propionyl CoA is further metabolised to
succinyl CoA which enters the TCA cycle.
Oxidation of odd chain fatty acids

22. propionyl CoA D-Methylmalonyl CoA
L-Methylmalonyl CoASuccinyl CoA
ATP
AMP+PPi
propionyl CoA
carboxylase
Methylmalonyl CoA
epimerase
Methylmalonyl CoA
mutase
CH2
CO-S-CoA
CH3
H-C-COO-
CO-S-CoA
CH3
-OOC-C-H
CO-S-CoA
CH3
CH2
CO-S-CoA
CH2
COO-
CO2
B12
Biotin

23. Methylmalonic Acidemia-
It is due to defect in the enzyme
methylmalonyl CoA mutase or deficiency of
vitamin B12.
There is accumulation of methylmalonic acid
in body,
Followed by its excretion in the urine.
It cause sever acidosis, damages the CNS &
retards the growth.

24.  β-oxidation occurs in modified form in peroxisomes.
The FADH2 which are synthesized in β-oxidation (by
acyl CoA dehydrogenase) are not transferred to ETC,
but handed over to O2.
This results in the formation of H2O2 .
There is no ATP synthesis in peroxisomal β-oxidation.
It is now believed that, the peroxisomes carry out the
initial oxidation of long chain fatty acids which is
followed by mitochondrial oxidation.
Peroxisomal oxidation is induced by high fat diet and
administration of hypolipidemic drugs.
β-oxidation in peroxisomes

25. R-CH2-CH2-CH2-C-SCoA
O
=
FAD
FADH2
Acyl-CoA
Acyl-CoA
dehydrogenase
R-CH2-CH=CH-C-SCoA
O
=
Trans Enoyl-CoA
H2O2
H2O
catalase

26. Zellweger syndrome
A rare disorder characterized by the absence of
peroxisomes in all tissues.
As a result, the long chain fatty acids are not
oxidized.
They accumulate in the various tissues like brain,
liver, kidney.
Hence disorder is also known as
cerebrohepatorenal syndrome.

27. This is the minor pathway for oxidation of FA.
Oxidation occur at α-carbon atom.
One carbon is removed from carboxyl end of
fatty acid as CO2.
It does not require CoA & does not generate ATP.
This process occur in brain & nervous tissue.
Roll of α-oxidation-
It convert even chain fatty acid to odd chain fatty acid
which are the constituent of complex lipids in the brain.
α-Oxidation of fatty acids

28. CH3-(CH2)n-CH2-COO-
Fatty acid
CH3-(CH2)n-CH2-COO-
OH
-
CH3-(CH2)n-C-COO-
O=
CH3-(CH2)n-COO-
monoxygenase O2, Fe++, Vit. C
L-hydroxy fatty acid
dehydrogenase
decarboxylase
CO2

29. Refsum’s disease
A rare but sever neurological disorder.
Characterized by cerebral ataxia & peripheral
neuropathy.
Affected patients shows accumulation of fatty acid,
phytanic acid.
It caused by a defect in the α-oxidation due to
deficiency of enzyme phytanic acid hydoxylase.
Which is require for the hydroxylation of phytanic
acid derived from dietary chlorophyll by α-oxidation.
Phytanic acid contains a methyl gr. On C3 that block
beta oxidation.

30. ω-oxidation of fatty acids
This is the minor pathway for oxidation of FA.
It involve the hydroxylation followed by
oxidation of omega carbon atom of FA.
This reaction take place in the ER and require
cyto P450, NADPH.
CH3-(CH2)n- COOH
OHCH2-(CH2)n- COOH
COOH-(CH2)n- COOH
Hydroxylase cyto P450
Fatty acid
Dicarboxylic acid

31. Oxidation of fatty acids
& metabolic water
Fatty acid oxidation (even other forms of
aerobic respiration) is accompanied by the
production of water, referred to metabolic
water.
For instance, when one molecule of palmitic acid
is oxidized, it releases 16 molecules of water.

32. Example