β-oxidation of fatty acid
Fat
• Fats are important source of energy as (1gm of fat gives
9 kcal energy).
• Mainly as triacylglycerols (triglycerides) in adipose
cells
• Constitute 84% of stored energy
• Protein - 15%
• Carbohydrate (glucose or glycogen) - <1%
2
β-oxidation of fatty acid
• β-oxidation of fatty acid- The break down of a
fatty acid to acetyl-CoA.
• Occurs in the mitochondria
• Process is strictly aerobic
• After production Acetyl-CoA is fed directly into the
Krebs cycle
• It occurs in many tissues including liver, kidney
and heart.
• Fatty acids oxidation doesn't occur in the brain
o There are several types of fatty acids oxidation.
(1) β- oxidation of fatty acid
(2) α- oxidation of fatty acids
(3) ω- oxidation of fatty acids
• The beta oxidation of fatty acids involve
three stages:
1.Activation of fatty acids in the cytosol
2.Transport of activated fatty acids into
mitochondria (carnitine shuttle)
3.Beta oxidation proper in the mitochondrial
matrix
1) Activation of FA:
This proceeds by FA thiokinase (acyl COA
synthetase) present in cytosol
Thiokinase requires ATP, COA SH, Mg++. The
product of this reaction is FA acyl COA and
water.
2- Transport of fatty acyl CoA from cytosol into
mitochondria:
• Long chain acyl CoA traverses the inner
mitochondria membrane with a special
transport mechanism called Carnitine shuttle.
The cytosol
The matrix
2-Transport of acyl CoA into the mitochondria
(rate-limiting step)
1. Acyl groups from acyl COA is transferred to carnitine
to form acyl carnitine catalyzed by carnitine
acyltransferase I, in the outer mitochondrial
membrane.
2. Acylcarnitine is then shuttled across the inner
mitochondrial membrane by a translocase enzyme.
3. The acyl group is transferred back to CoA in matrix by
carnitine acyl transferase II.
4. Finally, carnitine is returned to the cytosolic side by
translocase, in exchange for an incoming acyl carnitine.
3. Proper of β – oxidation in the mitochondrial
matrix
There are 4 steps in β – oxidation
Step I – Oxidation by FAD linked dehydrogenase
Step II – Hydration by Hydratase
Step III – Oxidation by NAD linked dehydrogenase
Step IV – Thiolytic clevage Thiolase
The first reaction is the oxidation of acyl CoA by
an acyl CoA dehyrogenase to give α-β
unsaturarted acyl CoA (enoyl CoA).
FAD is the hydrogen acceptor.
The second reaction is the hydration of the
double bond to β-hydroxyacyl CoA (p-
hydroxyacyl CoA).
• The third reaction is the oxidation of β-
hydroxyacyl CoA to produce β-Ketoacyl CoA a
NAD-dependent reaction.
• The fourth reaction is cleavage of the two
carbon fragment by splitting the bond
between α and β carbons
• By thiolase enzyme.
• The release of acetyl CoA leaves an acyl CoA
molecule shortened by 2 carbons.
• This acyl CoA molecule is the substrate for the
next round of oxidation starting with acyl CoA
dehydrogenase.
• Repetition continues until all the carbons of the
original fatty acyl CoA are converted to acetyl
CoA.
• In the last round a four carbon acyl CoA (butyryl
CoA) is cleaved to 2 acetyl CoA.
• Energetics of FA oxidation
e.g. Palmitic (16C):
1.β-oxidation of palmitic acid will be repeated 7
cycles producing 8 molecules of acetyl COA.
2.In each cycle FADH2 and NADH+H+ is produced
and will be transported to the respiratory
chain.
• FADH2 2 ATP
• NADH + H+ 3 ATP
• So 7 cycles 5x7 = 35 ATP
3. Each acetyl COA which is oxidized in citric
cycle gives 12 ATP (8 x 12 = 96 ATP)
4. 2 ATP are utilized in the activation of fatty
acid (It occurs once).
• Energy gain = Energy produced - Energy
utilized
• = 35 ATP + 96 ATP - 2 ATP = 129 ATP
