-OXIDATION
Manoj Sigdel
-Oxidation of Fatty Acid
Fatty acid in body mostly oxidised by -oxidation
(other types are: alpha oxidation and omega
oxidation)
Oxidation of fatty acid on the carbon
Removal of 2 carbon fragment at a time; Acetyl CoA
Tissue location for oxidation
Most of the tissue in the body (However,
brain, erythrocytes and adrenal medulla cannot
utilize fatty acids for energy requirement)
Manoj Sigdel
STEPS OF -OXIDATION
1) Activation of fatty acid occuring in cytosol.
2) Transport of fatty acids into mitochondria.
-Oxidation proper in mitochondrial matrix.
Manoj Sigdel
Activation of Fatty Acid
(Cytosol)
Mg 2+
Mg 2+
/Thiokinase
Activation of
fatty acid to
Acyl CoA
R-CH2-CH2COOFatty Acid
AT
3 diff thiokinase to activate;
P Pyrophosphatas
Thiokinas
long chains (10-20),
medium chain (4-12),
e
e
PPi
PPi
short chain (<4)
O
R-CH2-CH2-C-AMP
Acyladenylate
CoA
SH
AMP
O
R-CH2-CH2-C-CoA
Acyl CoA
TRANSPORT OF ACYL COA
INTO MITOCHONDRIA
acyl group of acyl coA is transferred to carnitine
(-hydroxy -trimethyl aminobutyrate),catalysed
by Carnitine Acyl Transferase I (CAT
I),present on outer mitochondrial membrane or
outer surface of inner mitochondrial membrane.
the acyl carnitine is transported across the
membrane to mitochondrial matrix by carnitine
acyl translocase (CAT).
Carnitine Acyl TransferaseII(CATII) found on
the inner surface of inner mitochondrial
membrane converts acyl-carnitine to acyl CoA.
Transport of Fatty Acid in
Mitochondria
From Cytosol..Carnitine
Carnitine transport
system
Inner
Cytosol
Acyl
CoA
Carniti
ne
CAT-I
CoASH
Acyl
Carnitine
Mitochond
rial
membrane
Carrier
Protein
(Carnitin
e acyl
transloc
ase)
Mitochondrial
Matrix
Carniti
ne
Acyl
CoA
CAT-II
Acyl
Carnitine
CoASH
-OXIDATION PROPER
oxidation: the acyl CoA undergoes
dehydrogenation by acyl CoA dehydrogenase.
hydration: the enoyl CoA hydratase brings
about the hydration of double bond to form hydroxy acyl CoA.
oxidation: -hydroxy acyl CoA dehydrogenase
catalyses the oxidation to form -keto acyl
CoA.
cleavage: the thiolase cleaves acetyl CoA from
acyl CoA.
11
ENERGETIC OF PALMITIC ACID
OXIDATION
MECHANISM
ATP YIELD
-OXIDATION 7 CYCLES
7 FADH2
14
7 NADH
21
FROM 8 ACETYL COA
EACH ACETYL COA PROVIDES 12
ATP
96
TOTAL ENERGY FROM 1 MOLECULE
OF PALMITOYL COA.
131
ENERGY UTILIZATION FOR
ACTIVATION
NET YIELD
129
Oxidation of odd chain fatty acids
Oxidation of odd chain fatty acids is
similar to that of even chain fatty acids.
At the end 3 carbon unit, propionyl CoA is
produced.
Propionyl CoA is converted into succinyl
CoA.
Succinyl CoA is an intermediate in TCA
cycle
So, propionyl CoA is gluconeogenic.
Conversion of propionyl CoA to succinyl CoA
CH3
I
CH2
I
CO-S-CoA
Propionyl CoA
COOI
TCA
CH2
I
CH2
I
CO-S-CoA
Succinyl CoA
Propionyl CoA
carboxylase
CO2
Biotin
ATP
ADP + Pi
CH3
I
H - C- COOI
CO-S-CoA
D-methyl malonyl CoA
Methyl malonyl
CoA recemase
Methyl malonyl
CoA mutase
Vitamin B12
CH3
I
OOC C - H
I
CO-S-CoA
L - methyl malonyl CoA
Sudden infant death syndrome (SIDS)
Unexpected death of healthy infants, usually
overnight
Due to deficiency of medium chain acyl CoA
dehydrogenase.
Glucose is the principal source of energy, soon after
eating or feeding babies.
After a few hours, the glucose level and its utilization
decrease and the rate of fatty acid oxidation must
simultaneously increase to meet the energy needs.
The sudden death in infants is due to a blockade in
-oxidation caused by a deficiency in medium chain
acyl CoA dehydrogenase (MCAD)
Jamaican vomiting sickness
This disease is characterized by severe
hypoglycemia, vomiting, convulsions, coma
and death.
lt is caused by eating unriped ackee fruit
which contains an unusual toxic amino acid,
hypoglycin A.
This inhibits the enzyme acyl CoA
dehydrogenase and thus -oxidation of fatty
acids is blocked, leading to various
complications
Oxidation of unsaturated
fatty acid
Due to the presence of double bonds, the
unsaturated fatty acids are not reduced to the same
extent as saturated fatty acids.
Therefore, oxidation of unsaturated fatty acids, in
general, provides less energy than that of saturated
fafty acids.
Most of the reactions involved in the oxidation of
unsaturated fatty acids are the same as found in the
beta-oxidation of saturated fatty acids.
However, the presence of double bonds poses
problem for beta-oxidation to proceed. This is
overcome by two additional enzymes-an isomerase
and a reductase.
-oxidation
Oxidation of fatty acids on -carbon atom is
known as -oxidation.
In this, removal of one carbon unit from the
carboxyl end.
Energy is not produced.
Hydroxylation occurs at -carbon atom.
It is then oxidized to -keto acid.
This, keto acid undergoes decarboxylation,
yielding a molecule of CO2 & FA with one
carbon atom less.
Occurs in peroxisomes.
- oxidation is mainly used for fatty acids
that have a methyl group at the beta-carbon,
which blocks beta- oxidation.
Major dietary methylated fatty acid is
phytanic acid.
It is derived from phytol present in
chlorophyll, milk & animal fats.
Propionyl-CoA is released as a result of beta oxidation when the beta carbon is substituted)
Refsums disease
Due to deficiency of the enzyme -hydroxylase
(phytanic acid oxidase)
oxidation does not occur.
Phytanic acid does not converted into compound
that can be degraded by beta oxidation.
Phytanic acid accumulates in tissues.
Symptoms:
Severe neurological symptoms, polyneuropathy,
retinitis pigmentosa, nerve deafness & cerebellar
ataxia.
Restricted dietary intake of phytanic acid (including
milk-is a good source of phytanic acid)
Omega ( )- oxidation
Minor pathway, takes place in microsomes (ER) .
Catalyzed by hydroxylase enzymes involving
NADPH & cytochrome P-450.
Methyl (CH3) group is hydroxylated to CH2OH &
subsequently oxidized with the help of NADPH to
COOH group to produce dicarboxylic acids.
After these three steps, either end of the fatty
acid can be attached tocoenzyme A. The
molecule can then enter the mitochondrion and
undergo oxidation. The final products after
successive oxidations includesuccinic acid
(HOOC-(CH2)2-COOH), which can enter thecitric
acid cycle, andadipic acid ((CH2)4(COOH)2).
The process is normally a minor catabolic
pathway for medium-chain fatty acids (10-12
carbon atoms), but becomes more important
when oxidation is defective.
When -oxidation is defective & dicarboxylic
acids are excreted in urine causing dicarboxylic
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